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Biomedical subjects

H Persson

Publications and source records attributed to H Persson.

At least 253 records · Page 14Linked to original sources
PubMed1989

A cell line producing recombinant nerve growth factor evokes growth responses in intrinsic and grafted central cholinergic neurons.

The rat beta nerve growth factor (NGF) gene was inserted into a mammalian expression vector and cotransfected with a plasmid conferring resistance to neomycin into mouse 3T3 fibroblasts. From this transfection a stable cell line was selected that contains several hundred copies of the rat NGF gene and produces excess levels of recombinant NGF. Such genetically modified cells were implanted into the rat brain as a probe for in vivo effects of NGF on central nervous system neurons. In a model of the cortical cholinergic deficits in Alzheimer disease, we demonstrate a marked increase in the survival of, and fiber outgrowth from, grafts of fetal basal forebrain cholinergic neurons, as well as stimulation of fiber formation by intact adult intrinsic cholinergic circuits in the cerebral cortex. Adult cholinergic interneurons in intact striatum also sprout vigorously toward implanted fibroblasts. Our results suggest that this model has implications for future treatment of neurodegenerative diseases.

Acetylcholinesterase↗
PubMed1989

Transient expression of the cholecystokinin gene in male germ cells and accumulation of the peptide in the acrosomal granule: possible role of cholecystokinin in fertilization.

Expression of the gene encoding the neurotransmitter/neuromodulator cholecystokinin (CCK) was demonstrated in testis of several different species. Two testicular CCK mRNA transcripts of different sizes were detected, and studies on the ontogeny of CCK gene expression indicated that the gene was expressed in male germ cells. In situ hybridization revealed CCK mRNA-expressing cells in the peripheral parts of the seminiferous tubules. Biochemical identification showed that the majority of prepro-CCK products in the testis represented pro-CCK. Immunofluorescence studies revealed CCK-like peptides primarily in spermatocytes and spermatids of mouse, rat, and monkey. Immuno electron microscopy of monkey testis demonstrated CCK immunoreactivity in the acrosomal granule of spermatids. Hence, an interesting possibility is that CCK peptides can be released during the acrosome reaction and thus may be of importance in the fertilization process.

Acrosome↗
PubMed1989

Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer.

Fasting is generally accompanied by a decrease in energy metabolism and hormones. On the other hand, indirect evidence has suggested that the response to adrenergic agonists may be maintained or even increased in malnutrition. The present study evaluated whether weight-losing patients with and without cancer have increased plasma concentrations of catecholamines and different responses to intravenously infused adrenaline compared to weight-stable individuals. Eight malnourished cancer and 10 non-cancer patients (11% weight loss) were compared to seven well-nourished and weight-stable patients. Adrenaline was infused i.v. at a rate of 0.005 microgram min-1 kg-1 body weight during 40 min followed by a 40 min rest period (without infusion) and then a final 40 min period with i.v. adrenaline infusion (0.02 microgram min-1 kg-1 body weight). Plasma glycerol concentration at fast was higher in weight-losing patients compared to weight-stable individuals. Whole body oxygen uptake, carbon dioxide production, heart rate and plasma concentrations of free fatty acids (FFA) increased while the mean arterial pressure decreased significantly in response to adrenaline infusion at 0.02 microgram kg-1 min-1 in both weight-losing and weight-stable patients. Adrenaline at 0.005 microgram kg-1 min-1 increased plasma FFA levels by 19% (P less than 0.05) in weight-losing patients while no significant alteration was observed in well-nourished patients. Adrenaline infusion at 0.02 microgram kg-1 min-1 decreased the mean arterial blood pressure and stimulated respiratory gas exchange and heart rate significantly more in weight-losing than in weight-stable patients. The slopes for oxygen uptake, carbon dioxide production, heart rate, plasma FFA and plasma glycerol vs. plasma adrenaline and noradrenaline were all significantly steeper (P less than 0.05-0.01) in malnourished patients than in well-nourished controls. The present study suggests an increased sensitivity to adrenaline in weight-losing patients compared to matched controls with normal nutritional state and stable weight.

Aged↗
PubMed1989

High frequency of in situ hybridization on thin plastic sections of human placenta with a cDNA probe for beta hCG.

We describe two different techniques with plastic embedding in in situ hybridization histochemistry (ISHH). Their applicability was demonstrated by use of human placenta of the tenth gestational week and a tritium-labeled cDNA probe for the beta-subunit of hCG. In the first method, ISHH was performed on whole pieces of tissue (en bloc ISHH) pretreated with a weak acid solution, embedded in methacrylate, and sectioned at 3 microns for autoradiography. In the second technique, en bloc ISHH was carried out on tissue pre-treated with the weak acid and thereafter with detergent to further facilitate probe penetration. An acrylic resin was used for embedding, and section thickness was reduced to 1 microns. With both techniques, beta hCG cDNA/mRNA hybrids were localized exclusively to the syncytiotrophoblast (ST), in agreement with a previous study using sections of frozen placentas for hybridization to the same probe. However, owing to the higher resolution of the plastic sections the reliability of this localization was greatly increased. The number of autoradiographic grains over the acrylic resin 1-microns sections was found to be considerably higher than that over the methacrylate 3-microns sections. This study showed that treatment of tissue with detergent before en bloc ISHH, with subsequent embedding in acrylic resin and sectioning at 1 microns, gives high resolution in combination with a high signal-to-noise ratio after autoradiography. As the acrylic resin permits cutting of ultrathin sections, the results suggest that the technique may become useful for ISHH studies at the subcellular level.

Autoradiography↗
PubMed1989

Results of primary radiation treatment of endometrial carcinoma. 20 years' experience of an unselected material from the north of Sweden.

An unselected material of endometrial carcinoma from the northern part of Sweden, treated during the years 1963-1982 is presented. The material comprises 1,114 patients treated almost uniformly. With few exceptions the patients received primary irradiation, usually with radium packing according to a modified Heyman method. Operable patients underwent total hysterectomy and bilateral salpingo-oophorectomy six weeks after the radiation treatment. Patients with contraindications to surgery had a curettage three months after radiation treatment and if cancer was still present surgery was considered. The 5-year survival rate in stage 1 treated with irradiation and surgery was 91%, and after correction for intercurrent death 93%. The 5-year survival rate in stage I as a whole was 82% and corrected for intercurrent death 90%. The survival rate in the whole material was 76% and after correction for intercurrent death 84%.

Female↗
PubMed1989

Whole body gas exchange: amino acid and lactate clearance as indicators of initial and early allograft viability in liver transplantation.

A method for the rapid assessment of liver allograft circulation and function after liver transplantation is described. In 12 patients undergoing liver transplantation continuous recording of whole body energy production was made on the basis of gas exchange measurements during the surgical procedure. Oxygen consumption decreased rapidly by 25% when the blood supply to the native liver was interrupted. After the anhepatic period, there was a sharp increase of oxygen consumption with successful reperfusion of the allograft. Carbon dioxide production fell by 14% and returned to preanhepatic values after successful declamping. In two cases with suboptimal reperfusion the return of gas exchange values was slow and incomplete. Results from the studies of whole body energy production were compared with biochemical measurements. No significant accumulation of amino acids occurred during the anhepatic period, but in the two patients with incomplete revascularization, clearance of amino acids, after the anhepatic phase, was impaired and plasma amino acids accumulated. The same pattern was found for plasma lactate levels. By the techniques described in this article, rapid and reliable assessment of initial and early graft function in hepatic transplantation is possible. This is of great value for the intraoperative and early postoperative assessment and planning of surgical and anesthesiologic strategies.

Adolescent↗
PubMed1988

Expression of the beta-nerve growth factor gene in hippocampal neurons.

In situ hybridization with complementary DNA probes for nerve growth factor (NGF) was used to identify cells containing NGF messenger RNA in rat and mouse brain. The most intense labeling occurred in hippocampus, where hybridizing neurons were found in the dentate gyrus and the pyramidal cell layer. The neuronal identity of NGF mRNA-containing cells was further assessed by a loss of NGF-hybridizing mRNA in hippocampal areas where neurons had been destroyed by kainic acid or colchicine. RNA blot analysis also revealed a considerable decrease in the level of NGF mRNA in rat dentate gyrus after a lesion was produced by colchicine. This lesion also caused a decrease in the level of Thy-1 mRNA and an increase in the level of glial fibrillary acidic protein mRNA. Neuronal death was thus associated with the disappearance of NGF mRNA. These results suggest a synthesis of NGF by neurons in the brain and imply that, in hippocampus, NGF influences NGF-sensitive neurons through neuron-to-neuron interactions.

Animals↗
PubMed1988

Rat beta-nerve growth factor sequence and site of synthesis in the adult hippocampus.

A rat beta-nerve growth factor (NGF) genomic sequence encoding the entire 3' exon of preproNGF was cloned, and its nucleotide sequence was determined. Rat NGF shows very high homology with other known NGFs in both the prepropeptide and the 3' untranslated regions. The presumptive signal sequence, the cysteine residues important for tertiary structure, possible glycosylation sites, and dibasic amino acids required for proteolytic cleavage to mature NGF are conserved across species. Comparison of the hydrophobicity plots and amino acid sequences revealed an evolutionary divergent domain on the external surface of NGF, which may account for the poor immunologic crossreactivities of the various NGFs. In situ hybridization with a rat-specific oligodeoxynucleotide indicated high levels of NGF mRNA synthesis in both hippocampal granule and pyramidal cell layers. These results are consistent with one role for NGF in the CNS as a neuronally released, retrogradely transported neurotrophic factor for basal forebrain cholinergic neurons.

Amino Acid Sequence↗
PubMed1988

Aspects of the protein and the lipid composition of myelinoid Marchi-positive bodies from mammalian spinal cord.

The fraction floating on 0.32 M sucrose was isolated from normal mammalian spinal cord and analyzed with regard to protein and lipid composition. Comparisons were made with the myelin fraction isolated from the same spinal cord. A close relationship between the two fractions was indicated by a similar protein banding on SDS-polyacrylamide gel electrophoresis. The relative amounts of various proteins however were different and some high molecular weight proteins appeared unique to the floating fraction. The phospho- and galactolipid patterns, as revealed by thin-layer chromatography, were similar in the floating and the myelin fractions. The proportion of hydrophobic lipids, such as sterols and isoprenyl derivatives, was higher in the floating fraction. Bands co-migrating with cholesterol esters were detected only in the floating fraction from guinea pigs. Marchi-positive material of possible paranodal origin is enriched in the floating fraction. The present findings of a biochemical composition of the floating fraction closely resembling that of myelin is in line with the view that myelin turnover includes a step of degradation localized to the paranodal regions.

Animals↗
PubMed1988

Neuropeptide tyrosine in the rat adrenal gland--immunohistochemical and in situ hybridization studies.

The adrenal gland of the rat was analysed with immunohistochemistry and antisera to neuropeptide tyrosine, to the catecholamine-synthesizing enzymes tyrosine hydroxylase, phenyl-ethanolamine-N-methyltransferase, and to acetylcholinesterase and with in situ hybridization using a nick-translated 280 base pair deoxyribonucleic acid probe coding for exon 2 of the rat neuropeptide tyrosine gene. Neuropeptide tyrosine-like immunoreactivity was observed in three structures: chromaffin cells, medullary ganglion cells and nerve fibers. The chromaffin cells were of both the noradrenaline- and adrenaline-type. The ganglion cells did not seem to contain any catecholamine-synthesizing enzymes but exhibited a strong immunoreaction for acetylcholinesterase. They were thus in all probability cholinergic neurons. In situ hybridization using the nick-translated deoxyribonucleic acid probe to rat neuropeptide tyrosine messenger ribonucleic acid revealed a very high-grain density over the ganglion cells, a moderate density over the chromaffin cells and a low background over cortex, in agreement with the immuno-histochemical demonstration of neuropeptide tyrosine-like immunoreactivity both in chromaffin and ganglion cells. The intense neuropeptide tyrosine-like immunoreactivity and low content of neuropeptide tyrosine messenger ribonucleic acid suggest that the chromaffin cells have fairly large peptide stores but that the peptide turnover is low. In contrast, the ganglion cell bodies seem to contain low amounts of neuropeptide tyrosine-like immunoreactivity but exhibit a high neuropeptide tyrosine synthesis rate. Preliminary studies with the amine-depleting drug reserpine revealed an increase in messenger ribonucleic acid both in ganglion cells and medullary cells. In the chromaffin cells the highest activity was seen 3 and 4 days after injection, and the levels were down to normal after 8 days. The present findings demonstrate neuropeptide tyrosine synthesis and storage in two cell populations in the adrenal medulla. In situ hybridization with its cellular resolution can provide information on possible differential effects of drugs and experimental procedures on these two neuropeptide tyrosine stores.

Acetylcholinesterase↗
PubMed1988

Developmental and regional expression of beta-nerve growth factor receptor mRNA in the chick and rat.

Hybridization probes from the transmembrane region of the chick NGF receptor (NGF-R) that show high homology with the rat NGF-R were used to demonstrate an abundant 4.5 kb NGF-R mRNA in the chick embryo at E3.5. The level remained high until E12 but decreased to adult levels by E18. The highest levels at E8 were in spinal cord, bursa of Fabricius, gizzard, femoralis muscle, and skin. In situ hybridization to E7 embryos showed high expression of the NGF-R gene in spinal cord, particularly the lateral motor column, and in dorsal root, sympathetic, and nodose ganglia. NGF-R mRNA expression was observed throughout brain development and in all regions of the adult brain, with high levels in cerebellum and septum. Lymphoid tissues of chick and rat also expressed the receptor. The complex and widespread expression of NGF-R mRNA in areas not known to be NGF targets suggests broader functions for NGF.

Amino Acid Sequence↗
PubMed1988

Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla.

Adrenal Glands↗
PubMed1988

Nerve growth factor mRNA and protein in the testis and epididymis of mouse and rat.

In situ hybridization using beta-nerve growth factor (NGF) DNA probes was used to demonstrate NGF mRNA in spermatocytes and early spermatids of adult mouse. NGF mRNA-containing cells were also identified in the epithelium of convoluted ducts in mouse corpus epididymidis. Blot-hybridization analysis of RNA prepared from mouse testis and epididymis as well as from rat epididymis confirmed the presence of a 1.3-kilobase (kb) NGF mRNA in these tissues. In the rat testis, however, only a 1.5-kb NGF mRNA was found, corresponding in size to a minor NGF mRNA detected in the rat brain, heart, and epididymis. By using affinity-purified anti-NGF antibodies, NGF-like immunoreactivity was observed in germ cells of rat and mouse testis and in the lumen of epididymis. Extracts of both mouse epididymis and testis stimulated fiber outgrowth in cultured sympathetic ganglia, and the effect was blocked by antibodies to mouse NGF. A two-site enzyme immunoassay showed the presence of 10 and 70 ng of NGF per g of tissue in the mouse testis and epididymis, respectively. Furthermore, RNA blot analysis showed the presence of mRNA for the NGF receptor in mouse testis. These results suggest a nonneurotrophic role for NGF in the male reproductive system, possibly in survival maturation and/or motility of spermatozoa.

Animals↗