Search PubMed⌕ Search

Biomedical subjects

H Persson

Publications and source records attributed to H Persson.

At least 181 records · Page 10Linked to original sources
PubMed1991

Distinct functions for thyroid hormone receptors alpha and beta in brain development indicated by differential expression of receptor genes.

Thyroid hormones are essential for correct brain development, and since vertebrates express two thyroid hormone receptor genes (TR alpha and beta), we investigated TR gene expression during chick brain ontogenesis. In situ hybridization analyses showed that TR alpha mRNA was widely expressed from early embryonic stages, whereas TR beta was sharply induced after embryonic day 19 (E19), coinciding with the known hormone-sensitive period. Differential expression of TR mRNAs was striking in the cerebellum: TR beta mRNA was induced in white matter and granule cells after the migratory phase, suggesting a main TR beta function in late, hormone-dependent glial and neuronal maturation. In contrast, TR alpha mRNA was expressed in the earlier proliferating and migrating granule cells, and in the more mature granular and Purkinje cell layers after hatching, indicating a role for TR alpha in both immature and mature neural cells. Surprisingly, both TR genes were expressed in early cerebellar outgrowth at E9, before known hormone requirements, with TR beta mRNA restricted to the ventricular epithelium of the metencephalon and TR alpha expressed in migrating cells and the early granular layer. The results implicate TRs with distinct functions in the early embryonic brain as well as in the late phase of hormone requirement.

Animals↗
PubMed1991

Developmental and regional expression of choline acetyltransferase mRNA in the rat central nervous system.

The developmental and regional expression of choline acetyltransferase (ChAT) mRNA was examined in the rat brain and spinal cord by northern blot analysis and in situ hybridization. ChAT mRNA expression in the brain showed a biphasic increase during development, with a first peak at two weeks postnatally, a marked decrease by the third week, and a second increase between the third and fifth week after birth, indicating that emergence of the cholinergic phenotype occurs at different times in different brain regions. In the spinal cord, ChAT mRNA was detected at similar levels from embryonic stage 13 (E13) until birth, increasing thereafter until adulthood. In the adult rat central nervous system, high levels of ChAT mRNA were detected in the spinal cord and brain stem structures. Lower levels were seen in midbrain, septum, striatum, thalamus, and olfactory bulb. ChAT mRNA containing cells were identified by in situ hybridization in the olfactory tubercule, piriform cortex, striatum, several basal forebrain nuclei, and spinal cord. A nearly two-fold increase in adult spinal cord ChAT mRNA levels were seen one week after a bilateral crush lesion of the sciatic nerve, indicating that ChAT mRNA expression is regulated during motoneuron regeneration.

Animals↗
PubMed1991

Kidney transplantation in type 1 (insulin-dependent) diabetic patients. Early glomerulopathy.

The development of diabetic glomerulopathy in kidneys transplanted to diabetic patients was estimated in transplant biopsies and evaluated in relation to suspected clinical risk factors for diabetic nephropathy. Surgical biopsies were taken at baseline and at 24-36 months post-transplantation in 16 Type 1 (insulin-dependent) diabetic patients and 8 non-diabetic control subjects with a glomerular filtration rate more than 30 ml.min-1 at follow-up. Immunosuppressive therapy included cyclosporine in all but one case. Stereological methods were used to assess basement membrane thickness, volume fraction of mesangium per glomerulus, and volume fraction of matrix per mesangium. The volume fraction of interstitial tissue per cortex was estimated by light microscopy. After 2 years the basement membrane thickness had increased by 55 nm (SD 58 nm) in the diabetic group. This change was significantly different from that of 2 nm (SD 37 nm) in control subjects (p = 0.02). Mesangial volume fraction increased significantly by 0.04 (SD 0.03) in diabetic patients, and this change was significantly different from that of -0.01 (SD 0.04) in non-diabetic patients (p = 0.009). No change was detectable in the matrix expressed as fraction of mesangial volume. An increase in interstitial volume fraction from baseline to 2 years was observed, but was significant only in the diabetic group (p = 0.04). The changes in structural parameters did not correlate with mean values during follow-up of glycated haemoglobin or estimated protein intake, nor was any pattern discernible in the relationship to graft tissue types.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Degradation products of myelin-oligodendrocyte-associated proteins in a light CNS subcellular fraction.

The presence of degradation products of the myelin/oligodendrocyte glycoprotein (MOG) and a new myelin/oligodendrocyte associated protein, FD1, defined by a monoclonal antibody was established in a subfraction (the floating fraction, or FF) of adult rabbit CNS. The histochemical distribution of FD1 was determined by indirect immunofluorescence using conventional and confocal microscopy. FD1 was found to be present in oligodendrocytes, and at the outer rim of CNS myelin sheaths. Strong antibody reactivity was noted at nodes of Ranvier, as well as in regions with a high nodal density. No staining of compact myelin was seen. In the PNS, inner and outer cytoplasmic compartments of the Schwann cells as well as their cell bodies were stained, with no staining of compact myelin. The FF has previously been shown to be highly enriched in Marchi-positive bodies. These structures are situated paranodally in the CNS of myelinated nerve fibers, and their presence has been interpreted as reflections of myelin breakdown and turnover occurring in association with myelin sheath segments situated close to nodes at Ranvier in adult, normal vertebrate CNS. The present findings extend previous observations of partially degraded myelin-associated proteins in the FF, and give further results indicating that Marchi-positive bodies are aspects of intermediate stages in myelin catabolism.

Animals↗
PubMed1991

Cellular relationships of paranodal Marchi-positive bodies studied with monoclonal antibodies against partially degraded CNS myelin fragments.

Histochemical and electron microscopical studies have shown that Marchi-positive bodies in the normal mammalian CNS are associated with paranodal regions and it has been proposed that the formation of Marchi-positive bodies represents a step in the catabolic events of normal myelin turnover. After a two-step density gradient ultracentrifugation a light 'floating fraction' highly enriched in these structures can be collected and in the present study two monoclonal antibodies, FC4 and 3B5, were produced against proteins present in the floating fraction but absent from the myelin fraction. Immunohistochemical studies showed that these antibodies bound preferentially to the PNS-CNS transitional region and the glia limitans. Double-staining experiments demonstrated an extensive overlap in these regions with cells stained by antibodies against the astrocyte marker glial fibrillary acidic protein. Centrally in the white matter, FC4 and 3B5 mainly stained cells which also stained with the microglia lectin marker Bandeiraea simplicifolia isolectin B4. Three-dimensional reconstructions made from confocal microscopic scans showed that FC4/3B5-positive cells in the white matter extend processes enveloping paranodal Marchi-positive bodies and nodes of Ranvier. It is suggested that astrocyte-like and microglia-like cells both are participants in paranodal myelin turnover and that a division of labour with respect to, for example, protein degradation and immunological functions, may be present between the two cell types.

Animals↗
PubMed1991

Beta receptor antagonists in the treatment of heart failure.

The use of beta-receptor antagonists in the treatment of heart failure is controversial. Available data do not allow general recommendations regarding their use. In dilated cardiomyopathy, several studies suggest that long-term treatment in individual patients reduces symptoms and increases exercise capacity. Short-term treatment is usually not beneficial, except in patients with ischemically induced left ventricular dysfunction. In heart failure, post myocardial infarction and in chronic ischemic heart disease, no proper long-term study has been performed to evaluate its effects. However, patients with acute myocardial infarction tolerate beta blockers, despite the presence of left ventricular dysfunction and long-term prognosis is improved. Newer agents, some with ancillary properties, such as intrinsic activity and vasodilatation, may have advantages. In the future we need a better description of the cardiac status in our patients in order to be able to select those that will respond favorably to beta-receptor antagonists. The mechanisms by which some patients improve are still obscure. Protection against receptor downregulation, restoration of receptor density, protection against cardiotoxicity of catecholamines, and improvement in ischemic systolic and diastolic left ventricular function are all possible. The fear that beta-receptor antagonists are dangerous in heart failure is in most instances not warranted, but an initial deterioration may have to be accepted in order to gain long-term beneficial effects. Ongoing studies in both idiopathic cardiomyopathy and in postinfarction failure will hopefully help us to define the use of beta-adrenoceptor antagonists in the future.

Adrenergic beta-Antagonists↗
PubMed1991

Detection of neuropeptide Y-like immunoreactivity and messenger RNA in rat platelets: the effects of vinblastine, reserpine, and dexamethasone on NPY expression in blood cells.

Rat plasma contains high basal levels (220 pmol/liter) of neuropeptide Y (NPY)-like immunoreactivity (LI) compared to pig (30 pmol/liter) and man (25 pmol/liter). The platelet-enriched fraction (PEF), obtained from rat blood contained 10,061 pmol/g NPY-LI. However, in human and pig blood, the PEF contained very low levels of NPY-LI. Gradient centrifugation of rat blood showed the highest concentration of NPY-LI (10.8 +/- 0.4 pmol/g) in the platelet fraction. The mononuclear cell fraction contained 1.64 +/- 0.16 pmol/g, whereas only 0.56 +/- 0.06 pmol/g of NPY-LI was found in the red blood cell/polymorphonuclear cell fraction. Characterization of NPY-LI in rat plasma and platelets by high-pressure liquid chromatography showed one predominating peak which coeluted with synthetic NPY (1-36) as well as three minor peaks, one of which coeluted with oxidized NPY. Analysis of NPY messenger RNA (mRNA) in bone marrow of the rat revealed a 0.79-kb-long NPY mRNA. This size is intermediate to the 0.82-kb NPY mRNA in brain and the 0.76-kb NPY mRNA in spleen. The highest level of NPY mRNA in rat blood was found in the mononuclear cell fraction but NPY mRNA was also detected in the platelet fraction. No NPY mRNA was detected in bone marrow or blood from pig and rabbit or from human blood or bone marrow. Forty-eight hours after treatment of rats with vinblastine the content of NPY mRNA and NPY-LI in rat blood was decreased, while the level of NPY-LI in bone marrow was markedly enhanced. Reserpine treatment caused an increase in NPY mRNA content in bone marrow and spleen. After administration of dexamethasone the level of NPY mRNA increased in both spleen and peripheral blood cells with increased NPY-LI content in the spleen. It is concluded that in addition to megakaryocytes in spleen and bone marrow, platelets and possibly also lymphocytes/monocytes in peripheral blood of the rat contain NPY mRNA and peptide. The expression of NPY mRNA in bone marrow, spleen, and blood is influenced by vinblastine, reserpine, and dexamethasone.

Animals↗
PubMed1991

Hippocampal damage and kainic acid injection induce a rapid increase in mRNA for BDNF and NGF in the rat brain.

In situ hybridization and Northern blots were used to study expression of mRNAs for members of the nerve growth factor family in the rat brain following an excitatory stimulus. One hour after a unilateral needle insertion or saline injection into the dorsal hippocampus, the level of brain-derived neurotrophic factor (BDNF) mRNA increased markedly in granular neurons of the dentate gyrus and in the piriform cortex ipsilateral to the injection. The same treatment also increased the level of NGF mRNA in granular neurons of the ipsilateral dentate gyrus. The rapid increase in BDNF and NGF mRNA after a needle insertion or injection of saline was transient and preceded by an increase in c-fos mRNA in the same brain regions. In contrast to a needle insertion per se or a saline injection, 7 h after a unilateral injection of kainic acid into the dorsal hippocampus, the level of BDNF mRNA was dramatically increased in the ipsilateral hippocampus, as well as in the ipsilateral frontoparietal, piriform and perihinal cortex, the amygdaloid complex, claustrum, and ventromedial hypothalamus. A less pronounced increase was also seen in these brain areas on the contralateral side. Northern blots revealed that the level of BDNF mRNA increased 5- and 40-fold in the contra- and ipsilateral hippocampus, respectively, compared to sham-operated control animals. In contrast to BDNF and NGF, the level of hippocampus-derived neurotrophic factor/neurotrohin-3 (HDNF/NT-3) mRNA was not altered by either needle insertion or injection of saline or kainic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Distribution patterns of CCK and CCK mRNA in some neuronal and non-neuronal tissues.

Mutt and Jorpes (49) originally isolated cholecystokinin (CCK) from porcine intestine. Subsequently, it was recognized that CCK/gastrin-like material could be found in the rat brain (74), and it was later shown mainly to represent the C-terminal octapeptide (CCK-8) (2, 12-14, 48, 54, 55). These radioimmunoassay studies have been supplemented by numerous immunohistochemical investigations showing extensive CCK immunoreactive neuron systems in the brain and spinal cord (20, 26, 27, 31, 37, 40, 42, 44, 72, 75, 76). During recent years several groups have employed in situ hybridisation and radioactively labelled probes complementary to CCK mRNA and partly confirmed results from immunohistochemical studies but also revealed new interesting findings (3, 5, 6, 30, 41, 58, 64-66, 77). Several lines of evidence indicate that CCK-8 may act as a neurotransmitter or neuromodulator in many areas of the central nervous system. The development of new CCK antagonists has opened up new possibilities to understand the functional significance of CCK peptides in the neurons and other systems. The aim of the present article is to briefly review the distribution of some of the CCK systems and in this way define possible targets for these new types of drugs. Focus will be on cerebral cortex in view of the theme of the meeting, anxiety, on spinal cord as a basis for discussion of CCK and pain, and finally CCK/gastrin peptides in sperm will be discussed. The question of coexistence of CCK and dopamine in mesencephalic neurons is reviewed in a parallel article (28).

Animals↗
PubMed1991

Lymphocyte-mediated regulation of neurotransmitter gene expression in rat sympathetic ganglia.

It has been previously shown that sympathetic noradrenergic nerve fibers, in addition to supplying the smooth muscle of the splenic capsule, trabeculae and blood vessels, also form very tight appositions with lymphocytes of the periarteriolar lymphatic sheath. To determine whether there is a direct communication between the sympathetic neurons and the immune cells we have grown dissociated superior cervical ganglion (SCG) neurons together with splenic lymphocytes. Sympathetic neurons were grown both as mixed preparations (neurons and non-neuronal ganglion cells) and neuron-enriched preparations. These systems were used to investigate whether coculture with splenocytes alters neurotransmitter gene expression in SCG cultures. Northern blot analysis was used to measure changes in neurotransmitter mRNA expression. The results showed that expression of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, was significantly decreased when SCG cultures were grown in the presence of spleen cells compared to control SCGs grown either alone or in the presence of erythrocytes. When the mitogen concanavalin A (ConA) was used to stimulate the spleen cells in the cocultures the decrease in TH was more pronounced. In contrast, preprotachykinin-A (PPT-A) mRNA expression in cultured SCGs increased in the cocultures. Another neuropeptide, neuropeptide Y (NPY), showed different responses in the presence of stimulated vs. unstimulated splenocytes. NPY mRNA was slightly increased in the presence of resting spleen cells, but showed a 70% decrease when ConA was added to the cocultures. Thus, our results suggest that lymphocytes can differentially regulate neurotransmitter gene expression in sympathetic ganglia.

Animals↗
PubMed1991

Chronic treatment with SCH-23390, a selective dopamine D1 receptor blocker decreases preprotachykinin-A mRNA levels in nucleus tractus solitarii of the rabbit: role in respiratory control.

Acute intravenous administration of the selective D1 receptor blocker SCH-23390 resulted in an enhanced respiratory motor output as evidenced by the phrenic nerve activity, whereas local perfusion into the region of nucleus tractus solitarii had no effect. The increase in phrenic nerve activity was accompanied by a concomitant increase in the release of substance P in the region of nucleus tractus solitarii as measured by in vivo microdialysis technique. Chronic administration of SCH-23390 via subcutaneously implanted Alzet mini osmotic pumps, significantly decreased the level of preprotachykinin-A mRNA in the region of respiratory relay neurons in nucleus tractus solitarii but was without effect in the ventral medullary surface structure, wherein the central chemoreceptors are thought to be located. A smaller, but significant decrease was also seen in the striatum. The results suggest that chronic treatment with SCH-23390 leads to a disinhibition of an inhibitory dopaminergic input to the neurons in nucleus tractus solitarii from a suprapontine level, which may account for a subsequent inhibition of tachykinin-containing neurons in the nucleus tractus solitarii, the relay station for respiratory reflexes.

Animals↗
PubMed1991

Distribution of cholecystokinin mRNA and peptides in the human brain.

Expression of preprocholecystokinin mRNA was studied in regions of post mortem human brain using RNA blot analysis (Northern blot) and in situ hybridization. Northern blot analysis using a cDNA probe showed high levels of an approximately 0.8 kb preprocholecystokinin mRNA in all regions of neocortex examined. Lower levels of preprocholecystokinin mRNA were detected in amygdaloid body and thalamus. In situ hybridization analysis using the same cDNA probe revealed numerous weakly labelled neurons in different areas of human neocortex and less numerous neurons in hippocampus and amygdaloid body. High-performance liquid-chromatography and gel-chromatography combined with radioimmunoassay of cholecystokinin-like immunoreactivity from human cerebral cortex and caudate nucleus revealed two major forms, one coeluting with sulphated cholecystokinin-8 and the other coeluting with sulphated cholecystokinin-58. Two minor components coeluting with cholecystokinin-4 and cholecystokinin-5 were also detected. The finding of cholecystokinin-like immunoreactivity corresponding to cholecystokinin-8 and cholecystokinin-58 in caudate nucleus where no preprocholecystokinin mRNA was found, indicates the presence of these peptides in afferent nerve terminals.

Blotting, Northern↗
PubMed1991

Repeated electroconvulsive shock increases tachykinin and cholecystokinin mRNA expression in ventral periaqueductal gray.

The effect of repeated electroconvulsive shock (five shocks during 10 days) on preprocholecystokinin and preprotachykinin-A messenger RNA expression was studied in the mesencephalic periaqueductal gray and adjacent areas of rat using in situ hybridization histochemistry with specific oligonucleotide probes. An increased number of preprocholecystokinin and preprotachykinin-A messenger RNA hybridization positive neurons (+30% and +47%, respectively) in the Edinger-Westphal nucleus was observed following repeated electroconvulsive shock. In addition, both preprocholecystokinin and preprotachykinin-A messenger RNA expression, measured as grain density over single neurons, was significantly increased (+37% and +45%, respectively). The results indicate that cholecystokinin- and substance P-containing neurons in the Edinger-Westphal nucleus are activated by repeated electroconvulsive shock, which may be related to the antidepressant and analgesic effects of electroconvulsive shock treatment.

Animals↗
PubMed1991

Neuropeptide Y and catecholamine synthesizing enzymes and their mRNAs in rat sympathetic neurons and adrenal glands: studies on expression, synthesis and axonal transport after pharmacological and experimental manipulations using hybridization techniques and radioimmunoassay.

The effects of reserpine treatment (10 mg/kg, i.p.) on the content of neuropeptide Y-like immunoreactivity and catecholamines were compared with the levels of mRNA coding for neuropeptide Y, tyrosine hydroxylase and phenylethanolamine N-methyltransferase in rat sympathetic neurons and adrenal gland. A reversible depletion of neuropeptide Y-like immunoreactivity was observed in the right atrium of the heart, kidney and masseter muscle, while the immunoreactive neuropeptide Y content in the stellate and lumbar sympathetic ganglia and its axonal transport in the sciatic nerve increased following reserpine. The increase in the stellate ganglion was maximal at 48 h and absent 9 days after reserpine treatment. The expression of neuropeptide Y mRNA and tyrosine hydroxylase mRNA in both the stellate and the superior cervical ganglion increased earlier than the neuropeptide Y content, with a clear cut two-fold elevation at 24 h after reserpine. The increase in both mRNAs in the superior cervical ganglion and the depletion of neuropeptide Y, but not of noradrenaline, in terminal areas was prevented after pretreatment both with a nicotinic receptor antagonist (chlorisondamine) and with surgical preganglionic denervation. A marked (75-90%) depletion of neuropeptide Y-like immunoreactivity and adrenaline in the adrenal gland, concomitant with 3-4-fold increases in neuropeptide Y mRNA and tyrosine hydroxylase mRNA expression, was present at 24 h after reserpine treatment. Also in the adrenal gland, there was a reversal of the reserpine-induced increase in neuropeptide Y mRNA and tyrosine hydroxylase mRNA and depletion of neuropeptide Y and adrenaline following splanchnic denervation. Pharmacological, ganglionic blockade prevented the depletion of neuropeptide Y and the increased expression of neuropeptide Y mRNA, but not fully, the tyrosine hydroxylase mRNA elevation. In addition, a marked decrease in phenylethanolamine N-methyltransferase mRNA levels was noted after reserpine. This decrease was reversed by denervation and by ganglionic blockade. Denervation alone led to a small but significant decrease in all mRNAs examined both in the superior cervical ganglion and the adrenal medulla. The present data suggest that the depletion of neuropeptide Y-like immunoreactivity in sympathetic nerves and in the adrenal gland after reserpine is associated with a compensatory increase in neuropeptide Y synthesis and axonal transport, most likely due to increased nicotinic receptor stimulation. Whereas the reserpine depletion of neuropeptide Y in both sympathetic nerves and adrenal gland is related to neuronal activation, adrenal but not nerve terminal depletion of catecholamines can be prevented by the ganglionic blocker chlorisondamine.4+e difference in effect of pharmacological ganglionic

Adrenal Glands↗
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

Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis.

Kindling, induced by repeated subconvulsive electrical or chemical stimulations leads to progressive and permanent amplification of seizure activity, culminating in generalized seizures. We report that kindling induced by electrical stimulation in the ventral hippocampus leads to a marked and transient increase in mRNA for NGF and BDNF in the dentate gyrus, the parietal cortex, and the piriform cortex. BDNF mRNA increased also in the pyramidal layer of hippocampus and in the amygdaloid complex. No change was seen in the level of HDNF/NT-3 mRNA. The increased expression of NGF and BDNF mRNAs was not influenced by pretreatment with the NMDA receptor antagonist MK801, but was partially blocked by the quisqualate, AMPA receptor antagonist NBQX. The presumed subsequent increase of the trophic factors themselves may be important for kindling-associated plasticity in specific neuronal systems in the hippocampus, which could promote hyperexcitability and contribute to the development of epileptic syndromes.

Animals↗
PubMed1991

Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary.

Evolutionary conservation of members of the NGF family in vertebrates was studied by DNA sequence analysis of PCR fragments for NGF, BDNF, and NT-3 from human, rat, chicken, viper, Xenopus, salmon, and ray. The results showed that the three factors are highly conserved from fishes to mammals. Phylogenetic trees reflecting the evolution and speciation of the members of the NGF family were constructed. In addition, the gene for a fourth member of the family, neurotrophin-4 (NT-4), was isolated from Xenopus and viper. The NT-4 gene encodes a precursor protein of 236 amino acids, which is processed into a 123 amino acid mature NT-4 protein with 50%-60% amino acid identity to NGF, BDNF, and NT-3. The NT-4 protein was shown to interact with the low affinity NGF receptor and elicited neurite outgrowth from explanted dorsal root ganglia with no and lower activity in sympathetic and nodose ganglia, respectively. Northern blot analysis of different tissues from Xenopus showed NT-4 mRNA only in ovary, where it was present at levels over 100-fold higher than those of NGF mRNA in heart.

Amino Acid Sequence↗