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Biomedical subjects

H Persson

Publications and source records attributed to H Persson.

At least 235 records · Page 13Linked to original sources

Beneficial effects of sucralphate in radiation induced diarrhea. An open randomized study in gynecological cancer patients.

In an open randomized study including 51 consecutive patients with gynaecological malignancies sucralphate was daily administered to patients receiving pelvic irradiation. Sucralphate, an aluminium hydroxide complex of sulphated sucrose used in the treatment of gastric ulcer, seems to be of value in preventing radiation-induced bowel discomfort. The most objective parameter, frequency of diarrhoea was almost 50% less in the sucralphate groups as compared to the controls. The patients receiving sucralphate in general displayed only minor alterations in bowel habits even at the end of the radiation treatment. The number of patients requiring symptomatic therapy with loperamide were markedly lower in the sucralphate group. Subjective discomfort such as nausea, vomiting, loss of appetite were also less common. A reduction in acute reactions to irradiation increases the possibility of carrying through planned treatment and avoids unfavourable intermissions, and thus curing the patient with cancer in the pelvis by means of radiotherapy.

Diarrhea↗

Dysgerminoma of the ovary: treatment results in northern Sweden.

Thirteen patients with ovarian dysgerminoma were treated and followed up at the Department of Gynaecologic Oncology, University Hospital, Umeă between 1962 and June 1988. All except one had pure dysgerminoma. Ten patients had stage I, one stage II and two stage III disease. They underwent surgery, received radiotherapy, and have all been alive without evidence of disease, ten for more than 10 years, seven for over 20 years and four ever 25 years. One patient conceived and had two normal deliveries after conservative surgery and hemi-pelvic irradiation. The clinical presentation, treatment and outcome are discussed against the current shift in management of dysgerminoma towards increasingly conservative treatment.

Adolescent↗

Isoelectric focusing of membrane proteins: high resolution separation of myelin proteins.

A mixture of the nonionic detergent Triton X-100, the zwitterionic detergent 3-[(cholamidopropyl)dimethylammonio]-1-propanesulphonate (CHAPS), 9M urea and carrier ampholytes was found comparable to media containing sodium dodecyl sulfate in the capacity for solubilization of myelin proteins, including the highly hydrophobic proteolipid protein. The solubilized sample was incorporated into the polymerization mixture before moulding an ultrathin gel, with heat convection characteristics allowing a high wattage to be applied, thus allowing fast separation with high resolving power. Since the most basic protein in myelin focuses at a pH greater than 10, fast separation is essential in order to minimize decay of the cathodic end of the pH gradient.

Altretamine↗

Characterization of antibodies to synthetic nerve growth factor (NGF) and proNGF peptides.

Sequence data for the mature nerve growth factor (NGF) protein and its precursor are available from molecular cloning of the NGF gene in several species, including mice, humans, rats, and chickens. Hydrophilicity analysis of the predicted rat and chicken prepro-NGF was carried out to locate putative antigenic determinants. Eight peptides were selected and synthesized based on hydrophilicity profiles. Two peptides represent sequences in the rat (and mouse) pro-NGF, one peptide (our peptide P3) represents a highly conserved region of the mature NGF protein (identical in humans, mice, rats, and chickens), two peptides are specific for the mature chicken NGF, and the remaining three peptides are specific for the mature rat NGF (each with only one amino acid substitution compared with corresponding segments of the mouse NGF). For immunization, the peptides were conjugated to keyhold limpet hemocyanin and used to produce antisera in rabbits. After bleeding, peptide-specific antibodies were purified on affinity columns prepared by coupling each of the synthetic peptides. The different peptide antisera and affinity-purified antibodies then were characterized by enzyme-linked immunoassay (ELISA) and immunohistochemistry of the male mouse submandibular gland, a rich exocrine source of NGF. ELISA analysis showed that all peptide antisera bound two to four orders of magnitude better than normal rabbit serum to a coat of their proper peptide. The higher binding was retained by the purified peptide antibodies compared with normal rabbit immunoglobulin. Specific tests, in which one peptide antiserum was checked against different peptide coats in the ELISA, also showed two to four orders of magnitude higher binding of antibodies to the proper synthetic peptide. The peptide antibodies also were tested for their ability to bind to native mouse beta NGF coated to the immunoplates. Only antibodies raised to the conserved P3 peptide recognized native NGF to an extent similar to that obtained with polyclonal anti-NGF antibodies. Conversely, P3 was well recognized by several different NGF antisera. Immunohistochemically, both peptide antisera against the pro-NGF stained the perinuclear cytoplasm in the basal part of the cells of the granulated convoluted tubules in the mouse submandibular gland.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Development and regional expression of chicken neuroleukin (glucose-6-phosphate isomerase) messenger RNA.

Neuroleukin (NLK) is a protein identical with the glycolytic enzyme glucose-6-phosphate isomerase (GPI) that has been reported to support the survival of a subpopulation of neurons in embryonic dorsal root ganglia and spinal cord neurons in culture. In this report we have studied the developmental expression of NLK mRNA in the chick embryo in order to evaluate its possible role as a neurotrophic factor. The chicken gene encoding NLK was isolated by cross-hybridization to a mouse NLK cDNA clone. A DNA fragment from the chicken NLK gene with a 90% nucleotide sequence homology to mouse NLK cDNA encoding amino acids 310-355 was then used as a hybridization probe in a series of RNA-blots. In the entire embryo NLK mRNA was found already at embryonic day 3.5 (E3.5) and the level of expression was significantly decreased between E3.5 and hatching. Roughly similar levels of NLK mRNA were found in all tissues of the E8 embryo analyzed with the exception of the brain, which contained only low levels. When the developmental expression was analyzed in different tissues separately, NLK mRNA expression was found to decrease during development in the heart and bursa of Fabricius, whereas the level of mRNA in the brain showed a large increase shortly after hatching. The spinal cord and the pectoral and femoral muscles all showed high levels of NLK mRNA throughout development. In the adult chick, the highest levels of NLK mRNA were found in the muscle, brain, and kidney, where the NLK mRNA was estimated to account for approximately 0.1% of the total mRNA in these tissues. A widespread expression of NLK mRNA was observed in the adult brain with approximately similar levels in all brain regions tested. Similar results were also obtained when NLK mRNA expression was analyzed in adult rats. Our results show that developmental expression of the NLK gene is independently regulated in different tissues. The widespread and abundant expression of both the avian and rodent NLK gene is in accordance with its newly discovered identity as a glycolytic enzyme. Consequently, the developmental and adult pattern of NLK mRNA expression does not favour a specific trophic role for this protein in accordance with other known neurotrophic factors.

Animals↗

Cholecystokinin and tyrosine hydroxylase messenger RNAs in neurons of rat mesencephalon: peptide/monoamine coexistence studies using in situ hybridization combined with immunocytochemistry.

The cellular localization of neurons expressing cholecystokinin (CCK) and tyrosine hydroxylase (TH) mRNAs was analysed in rat ventral mesencephalon using in situ hybridization techniques with both complementary DNA and synthetic oligonucleotide probes. Cell bodies distributed throughout the substantia nigra, ventral tegmental area, interfascicular nucleus, midline raphe nuclei, and central and ventral periaqueductal grey matter were found to contain CCK mRNA or TH mRNA as indicated by high densities of grains overlying the perikarya. The in situ hybridization technique was combined with immunocytochemistry on the same tissue section to localize the peptide or enzyme within its respective mRNA-containing somata. In addition, the presence of TH immunoreactivity was demonstrated within cell bodies labeled for CCK mRNA and immunostaining for CCK was detected within TH mRNA-containing neurons. In the medial geniculate nucleus a strong labeling for CCKmRNA was observed, in spite of the fact that so far no CCK-like immunoreactivity has been demonstrated in perikarya in this nucleus. The specificity of the probes was verified by RNA blot hybridization. These results confirm recent double-labeling immunocytochemical studies and further characterize the coexistence of CCK and TH at the level of their mRNAs as well as their post-translational products in a large population of mesencephalic dopamine neurons known to project to forebrain areas.

Animals↗

Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain.

In situ hybridization histochemistry and RNA blots were used to study the expression of glutamic acid decarboxylase (GAD) mRNA in rats with or without a unilateral lesion of midbrain dopamine neurons. Two populations of GAD mRNA positive neurons were found in the intact caudate-putamen, substantia nigra and fronto-parietal cortex. In caudate-putamen, only one out of ten of the GAD mRNA positive neurons expressed high levels, while in substantia nigra every second of the positive neurons expressed high levels of GAD mRNA. Relatively few, but intensively labelled neurons were found in the intact fronto-parietal cerebral cortex. In addition, one out of six of the GAD mRNA positive neurons in the fronto-parietal cortex showed a low labeling. On the ipsilateral side, the forebrain dopamine deafferentation induced an increase in the number of neurons expressing high levels of GAD mRNA in caudate-putamen, and a decrease in fronto-parietal cortex. A smaller decrease was also seen in substantia nigra. However, the total number of GAD mRNA positive neurons were not significantly changed in any of these brain regions. The changes in the levels of GAD mRNA after the dopamine lesion were confirmed by RNA blot analysis. Hence, midbrain dopamine neurons appear to control neuronal expression of GAD mRNA by a tonic down-regulation in a fraction of GAD mRNA positive neurons in caudate-putamen, and a tonic up-regulation in a fraction of GAD mRNA positive neurons in fronto-parietal cortex and substantia nigra.

Animals↗

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

The fraction floating on 0.32 M sucrose when normal mammalian spinal cord homogenate is submitted to discontinuous density gradient centrifugation is highly enriched in Marchi-positive material. In situ this material is located along paranodal myelin sheath segments. We here show by immunoblotting that degradation products of the myelin-associated glycoprotein (MAG) and of the enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) is present in the Marchi-positive floating fraction but is not found in the myelin fraction. Since previous biochemical analyses of the floating fraction show a gross composition closely resembling myelin and since metabolic studies show the specific activity of incorporated amino acids to proceed with time from heavier to lighter myelin subfractions the results strongly suggest that normally occurring Marchi-positive bodies represents an intermediate stage in myelin catabolism.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Detection of nerve growth factor and its mRNA by separate and combined immunohistochemistry and in situ hybridization in mouse salivary glands.

Intense labelling of secretory cells in the male mouse submandibular gland was observed after in situ hybridization using mouse nerve growth factor (NGF) cDNA probes. Under the same conditions, sparse less intensely labelled cells were also found in the sublingual gland. Hybridization to a chicken NGF cDNA probe gave weak labelling on the glands in accordance with a weak cross-hybridization between mouse NGF mRNA and chicken NGF cDNA probes, whereas no labelling was seen using pUC9 DNA as a hybridization probe. A combination of in situ hybridization and immunohistochemistry was also carried out on the same sections of submandibular gland. A good correlation was seen between actively synthesizing and intensely immunoreactive cells in the gland. The technique described here allows the detection of individual cells synthesizing relatively low levels of NGF. The combination of in situ hybridization and immunocytochemistry on the same section should be particularly useful in cases where NGF is transported away from its site of synthesis.

Animals↗

Tubulointerstitial nephritis caused by the antiviral agent foscarnet.

The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymorphonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.

Adult↗

Regional distribution of neuropeptide Y mRNA in postmortem human brain.

The distribution of messenger RNA encoding neuropeptide Y (NPY) was studied in 11 different postmortem human brain regions using in situ hybridization histochemistry, and RNA blot analysis. In situ hybridization data revealed that the highest numerical density of labeled cells corresponded to neurons in accumbens area, caudate nucleus, putamen, and substantia innominata. Significantly fewer NPY mRNA-containing neurons were found in frontal and parietal cortex, amygdaloid body and dentate gyrus. No NPY mRNA-containing cells were found in substantia nigra. NPY mRNA-positive neurons from all regions studied showed relatively similar labeling, as revealed by computerized image analysis. Blot analysis showed an approximately 0.8 kb NPY mRNA in all brain regions studied, except in substantia nigra and cerebellum. Densitometric scanning of the autoradiograms revealed levels of NPY mRNA in the following order: putamen greater than caudate nucleus greater than frontal cortex (Brodmann areas 4 and 6) greater than temporal cortex (Brodmann area 38) greater than parietal cortex (Brodmann areas 5 and 7) greater than frontal cortex (Brodmann area 11). Hence, although NPY mRNA is widely distributed in neurons of the human brain large regional variation exists, with the highest expression in accumbens area and parts of the basal ganglia.

Aged↗

Expression of nerve growth factor receptor mRNA is developmentally regulated and increased after axotomy in rat spinal cord motoneurons.

In situ hybridization histochemistry and RNA blot analysis were used to study expression of nerve growth factor receptor (NGF-R) mRNA in rat spinal cord motoneurons. The results show that NGF-R mRNA is expressed at high levels in rat spinal cord motoneurons at the time of naturally occurring cell death. This expression is sustained, but reduced, during synapse formation and is subsequently greatly reduced in the adult spinal cord. A unilateral crush lesion of the sciatic nerve resulted in an 8-fold increase in NGF-R mRNA in adult rat spinal cord motoneurons 3 days after lesion, compared with the nonlesioned side. NGF-R mRNA induction was even more pronounced 7 and 14 days after lesion, reaching levels 12 times higher than those on the nonlesioned side. However, 6 weeks after lesion, when the motor function of the leg was largely restored, NGF-R expression had decreased to levels similar to those on the contralateral side. We therefore suggest that NGF-R mediates a trophic or axonal guidance function for developing and regenerating spinal cord motoneurons.

Animals↗