Biomedical subjects

C Nilsson

Publications and source records attributed to C Nilsson.

At least 91 records · Page 5Linked to original sources

PubMed1996

Cloning of cDNA encoding a putative chemoattractant receptor.

Based on polymerase chain reaction (PCR) utilizing degenerate primers directed to the second and sixth transmembrane domains of several G-protein-coupled neurotransmitter receptors and screening of a human B-lymphoblast cDNA library, we isolated a cDNA whose predicted amino acid sequence shows considerable homology with human chemoattractant receptors, e.g., 30% overall identity with the C5a anaphylatoxin receptors. The coding region consists of 1056 bp corresponding to 352 amino acid residues and giving an approximate molecular weight of 43 kDa. Northern blot analysis showed hybridizing transcripts in spleen, thymus, and lymph nodes, as well as in bone marrow and peripheral blood leukocytes. Message was also found in lymphoid tumor cell lines. Chromosome mapping with FISH/DAPI technique showed the corresponding gene to reside on human chromosome 14q11.2-q12. In accordance with the Genome Database Nomenclature the receptor was designated CMKRL1 ("chemoattractant receptor-like 1"). Stably transfected mammalian cells (CHO cells and LVIP2.0Zc reporter cells) expressing high levels of corresponding receptor RNA were analyzed for changes in cAMP concentration and cellular calcium fluxes. Chemokines tested to date (GRO-a, MCP-1, MCP-3, MIP-1a, MIP-1b, C5a, RANTES, and LTB4) have failed to elicit any reproducible response. Although the ligand for CMKRL1 could thus not be identified among chemotactic peptides, the high expression in lymphoid cells and tissues suggests that the receptor may function in the regulation of the inflammatory system.

Amino Acid Sequence↗

PubMed1996

Differences in the neuropeptide Y-like immunoreactivity of the plasma and platelets of human volunteers and depressed patients.

In this study, patients with recurrent major depression were found to have significantly lower neuropeptide Y-like immunoreactivity (NPY-LI) in platelet-poor plasma (p < 0.01) and significantly higher NPY-LI in platelets (p < 0.001) compared to controls. Also, qualitative differences in the NPY-LI in platelet-poor plasma (PPP) and platelets were detected when the samples were analyzed by HPLC followed by RIA of the collected fractions.

Adult↗

PubMed1996

Expression of prepro-VIP derived peptides in the gastrointestinal tract of normal, hypothyroid and hyperthyroid rats.

Vasoactive intestinal polypeptide (VIP) is a widespread neuropeptide involved in the autonomic nervous control of smooth muscle activity, blood flow and secretion. To study the biosynthetic processing of the VIP precursor in the gut of normal, hypo- and hyperthyroid rats we used antisera against the five functional domains of the precursor molecule, prepro-VIP 22-79, peptide histidine isoleucine (PHI), prepro-VIP 111-122, VIP and prepro-VIP 156-170, to quantify and characterize VIP precursor peptides by radioimmunoassay and chromatography and examine their cellular localization and co-localization by immunohistochemistry. All five peptides were expressed in the gut but not in equimolar amounts as expected from the structure of the VIP precursor. A high concentration of PHV, the C-terminally extended form of PHI which includes prepro-VIP 111-122, was found in the small intestine. Immunohistochemically the prepro-VIP derived peptides were shown to coexist in neuronal elements. Changes in thyroid hormone status induced moderate changes in peptide expression in the gut, the most prominent being a 2-fold increase in all prepro-VIP derived peptides in the gastric fundus of hypothyroid rats. The findings indicate that differences in the post-translational processing of prepro-VIP exist in neurons of the rat gut and that hypo- and hyperthyroidism induce differential changes in peptide expression.

Animals↗

PubMed1996

Autocrine role of insulin-like growth factor II secretion by the rat choroid plexus.

Insulin-like growth factor II (IGF-II) is expressed and secreted by the choroid plexus and has been suggested to act as a trophic factor in the adult mammalian central nervous system. The aim of the present study was to investigate whether IGF-II has an autocrine role in the choroid plexus. Using in situ hybridization we demonstrate that IGF-II is primarily expressed in the epithelium of adult rat choroid plexus. Conditioned medium from primary cultures of purified rat choroid plexus epithelial cells, intact choroid plexus tissue, as well as rat CSF, displaced IGF-II binding to a 23 HMM melanoma cell line in an IGF-II radioreceptor assay. The presence of IGF-II and IGF binding protein-2 in conditioned medium was shown by Western immunoblot. The mitotic activity in choroid plexus epithelial cell cultures was quantified by immunohistochemical staining of bromodeoxyuridine incorporated into cell nuclei. A monoclonal antibody towards IGF-II inhibited cell division by 35%, while IGF-I increased the number of stained nuclei by 75%. Basic fibroblast growth factor stimulated cell division at low concentrations, but had no effect at high concentrations. Growth hormone had no effect. We conclude that IGF-II in the choroid plexus could have an autocrine role in the regulation of choroid plexus epithelial cell growth.

Animals↗

PubMed1996

Selective microsurgical sympathetic denervation of the rat pancreas.

Autonomic nerves have been implicated in the regulation of endocrine and exocrine pancreatic secretion. The purpose of the present study was, therefore, to develop a simple, reproducible technique for selective sympathetic denervation of the rat pancreas. Under ether anesthesia a midline laparotomy was performed, the pancreas and spleen were freed from adhesions. The peritoneum was incised over the superior and inferior pancreaticoduodenal arteries and the splenic artery at their origin. The incised areas were stained with 1% toluidine blue solution. The pancreaticoduodenal and splenic nerves were visualized and resected. 1, 2 and 3 weeks after the denervation procedure the norepinephrine (NE) content of the pancreatic tissue was determined. Cholinergic and nitric oxide synthetase (NOS)-immunoreactive nerve structures were identified by immunohistochemistry 1 week after denervation. In denervated tissue the NE content after 1 week was 98% lower than measured in controls. With time, there was a gradual increase of the NE content, although it reached only 25% of the values measured in sham-operated animals at 3 weeks. There was no concomitant denervation of the duodenum. Cholinergic and NOS nerve structures were still present 1 week after denervation.

Animals↗

PubMed1996

The role of luteinizing hormone-beta gene polymorphism in the onset and progression of puberty in healthy boys.

An immunologically anomalous LH with two point mutations in its beta-subunit gene (Trp8Arg and Ile15Thr) has recently been described. This polymorphism is common in Finland; 28% of the population are homo- or heterozygous for the variant allele. To assess the effect of the LH variant on LH action, we correlated its presence in a group of 49 healthy boys with the onset and progression of puberty. This group was followed-up longitudinally from a mean age of 11.7 +/- 0.1 yr for 3 yr at 3-month intervals. In addition, we studied the prevalence of the variant LH in boys with constitutional pubertal delay (testicular volume < or = 4 mL after 13.5 yr of age). The LH beta gene status of each subject in this study was judged from a single venous blood sample using two immunofluorometric LH assays with different combinations of monoclonal antibodies: one detecting both the variant and wild-type LH, and the other detecting only wild-type hormone. Of the boys with pubertal onset at a normal age, 36 (74%) were homozygous for the wild-type LH beta allele, 12 (24%) were heterozygous, and 1 (2%) was homozygous for the variant LH beta allele. Clear differences in pubertal parameters were found between the boys with normal and mutated (homo- or heterozygous) LH genotypes. During the follow-up, the boys with the mutated genotype had smaller testicular volumes (P < 0.03), were shorter (P < 0.02), had slower growth rates (P < 0.04), and had lower serum insulin-like growth factor I-binding protein-3 levels (P < 0.03) than the boys with the normal LH genotype. In the boys with delayed onset of puberty, the frequency of the variant LH beta allele did not differ from that in the reference population, indicating that the variant LH is not associated with conditions due to disturbed control of the reactivation of GnRH secretion. We conclude that during the progression of puberty, the variant LH may be less active in stimulating testicular growth than wild-type LH. Thus, the gene may affect tempo, contributing to the wide normal variation in pubertal progression in healthy boys. Our results also suggest that the variant LH not only affects the course of puberty, but is already involved in the regulation of the GH-insulin-like growth factor I axis during childhood.

Adolescent↗

PubMed1995

Delayed density-dependence in a small-rodent population.

The role of delayed density-dependent processes in the dynamics of animal populations poses a problem for ecologists; although generally assumed important in populations that show cyclic or chaotic fluctuations, little experimental evidence for such processes exist. Through manipulation of vole densities within enclosed areas it was shown that reproduction, recruitment, and body growth rate in introduced populations were negatively affected by high previous density. In addition, female movement patterns shifted, and territoriality as well as home-range size was increased after high density. The observed changes in female spacing-behaviour suggested that negative effects of previous density were partly mediated by social interactions, and agreed with the finding that smaller (less competitive) females were the ones suffering most from increased competition. Contrary to expectations from recent work, predation could be excluded as the cause of delayed density-dependence in this study. Instead, chemical analyses of a dominating food plant suggested that herbivory at high vole-density had delayed negative effects on food quality.

Animals↗

PubMed1995

Molecular characterization of the mouse prostanoid EP1 receptor gene.

A partial cDNA, corresponding to the mouse prostaglandin E2 receptor subtype EP1, was isolated from mouse brain cDNA using a degenerate primer PCR strategy. Using the cDNA fragment as a probe, the EP1 receptor gene was isolated and characterized. The gene consists of three exons, of which the first is non-coding, and is contained within a 3.5-kb region. The coding nucleotide sequence determined is identical to that of the published mouse EP1 cDNA. The positions of the introns correspond to those of the thromboxane A2 and prostaglandin D receptor genes. No alternative splicing of the EP1 receptor gene could be detected. PCR and specific primers designed from the genomic sequence were used to amplify the coding part of the isolated gene from kidney cDNA. The cDNA obtained was cloned into a eukaryotic expression vector, and stably transfected Chinese hamster ovary cell lines were established. The cells respond to prostaglandin E2 with intracellular Ca2+ mobilization, as expected for this prostanoid receptor subtype. In situ hybridization was used to localize the EP1 receptor transcript in different mouse tissues. Significant hybridization was detected only in the collecting ducts of the kidney, and in the paraventricular and supraoptic nuclei of the hypothalamus. The expression of the EP1 receptor in the hypothalamus suggests that this prostanoid receptor is involved in mediating the fever response evoked by prostaglandin E2.

Amino Acid Sequence↗

PubMed1995

Effect of thyroid hormones on vasoactive intestinal polypeptide gene expression in the rat cerebral cortex and anterior pituitary.

We report here data on the expression of the various sequences derived from the prepro-vasoactive intestinal polypeptide (VIP) precursor and VIP mRNA in the anterior pituitary gland and cerebral cortex of hypothyroid and hyperthyroid rats. Using specific antisera to each of the prepro-VIP sequences we demonstrated an increase of all prepro-VIP derived sequences, and accordingly, found that the number of cells expressing each of these sequences were markedly augmented in the anterior pituitary of the hypothyroid rats. This was accompanied by a marked increase in VIP mRNA. In the cerebral cortex of the hypothyroid rats no changes were observed. In the pituitary of hyperthyroid animals a significant decrease was seen for prepro-VIP 22-79, VIP and prepro-VIP 156-170, whereas in the cerebral cortex a significant increase was observed for prepro-VIP 22-79, PHI and VIP. We were not able to demonstrate any changes in VIP mRNA in the cerebral cortex or pituitary of the hyperthyroid rats. Gel permeation chromatography and reverse-phase HPLC of extracts from cerebral cortex showed elution profiles identical to the synthetic counterparts. The reported data provide further evidence of a tissue-specific expression and regulation of the VIP gene products.

Animals↗

PubMed1995

Photodynamic therapy for recurrent nasopharyngeal cancer.

OBJECTIVE: A pilot study to determine if photodynamic therapy could be a safe and efficacious treatment for recurrent or persistent nasopharyngeal cancer. DESIGN: A consecutive sample intervention study with comparison with historic control subjects. SETTING: Tertiary referral hospital. PATIENTS: All patients with recurrent or persistent nasopharyngeal cancer following radiation therapy were considered for treatment. Patients with tumors with a depth of more than 10-mm invasion on computed tomographic scans were excluded, as were patients with recurrent metastasis to the neck. Five patients were thus acquired during a 3-year period. INTERVENTION: Four patients were injected intravenously with hematoporphyrin derivative (2.5 mg/kg) and one patient with porfimer sodium (2 mg/kg) (Photofrin, Quadra Logic Technologies, Vancouver, British Columbia) 48 hours before treatment. The drug was activated by a 630-nm laser light passed down a 1-mm core quartz fiber to a miniaturized convex mirror positioned in the nasopharynx via the contralateral nasal cavity. This procedure was carried out under topical anesthesia. MAIN OUTCOME MEASURE: Survival was determined after a minimum follow-up of 4 years. RESULTS: To date, three of five patients treated have no evidence of disease, with follow-up times of 51, 52, and 60 months, respectively. The patient with the longest survival time had been unsuccessfully treated with 136 Gy of ionizing radiation preceding photodynamic therapy. CONCLUSIONS: Long-term tumor control can be achieved by photodynamic therapy in cases where very high doses of ionizing radiation have failed. The entire treatment can be accomplished in 30 minutes under topical anesthesia. The technique carries no serious side effects.

Adenocarcinoma↗

PubMed1995

Long-term protection against SIV-induced disease in macaques vaccinated with a live attenuated HIV-2 vaccine.

The aim of this study was to test the ability of a live attenuated human immunodeficiency virus type 2 (HIV-2) vaccine to protect cynomolgus monkeys against superinfection with a pathogenic simian immunodeficiency virus (SIVsm). This report is an update on our previously reported observation period of nine months. The new data here show that three of four monkeys vaccinated with live HIV-2 were protected against immunosuppression and SIV-induced disease during more than five years of follow-up. The quality of the immunity was permissive for infection, but monkeys that survived showed restricted viral replication in peripheral blood and lymph nodes. This study shows that it is possible to induce protection against a pathogenic heterologous primate lentivirus and to prevent disease in vaccinated monkeys even if infection is not prevented. These findings provide evidence that protection against AIDS can be achieved by immunization.

AIDS Vaccines↗

PubMed1995

Biosynthetic processing of preprovasoactive intestinal polypeptide in parasympathetic neurons of the sphenopalatine ganglion.

The precursor for rat vasoactive intestinal polypeptide (preproVIP) is processed by proteolytic cleavage into a signal peptide and five further functional domains: preproVIP 22-79, peptide histidine isoleucine (PHI), preproVIP 111-122, VIP, and preproVIP 156-170. To investigate the biosynthetic processing of preproVIP in peripheral parasympathetic neurons, the sphenopalatine ganglion and one of its projection areas, the nasal mucosa, were used. By immunohistochemistry it was shown that in the sphenopalatine ganglion, preproVIP-derived peptides are localized mainly in neuronal cell bodies, whereas in the nasal mucosa immunoreactivity was found only in nerve fibers and terminals. The peptides were quantified and characterized by radioimmunoassay, HPLC, and gel chromatography using antisera specific for the different precursor products. In the rat sphenopalatine ganglion, the different peptides were found in approximately equimolar amounts, with the exception of PHI and its C-terminally extended variant, PHV, which were present at considerably lower concentrations. However, in the nasal mucosa there was a preferential accumulation of VIP to at least three times the concentration of any of the other peptides. Our results suggest that all preproVIP-derived peptides are present and processed in the sphenopalatine ganglion but that there is a selective accumulation of VIP in the nerve terminals. This indicates that VIP is physiologically the most important transmitter among the preproVIP-derived peptides in parasympathetic nerves originating in the sphenopalatine ganglion.

Animals↗

PubMed1995

Total body irradiation: a neuropsychological risk factor in pediatric bone marrow transplant recipients.

Bone marrow transplantation (BMT) involves conditioning with cyclophosphamide and, for leukemic patients, total body irradiation (TBI). Based on the concern that this may lead to later neuropsychologic impairment in children, a longitudinal study was conducted. Thirty pediatric bone marrow transplant recipients, treated for leukemia or severe aplastic anemia (SAA), and their sibling donors, were given a neuropsychological examination in 1986 and 1988. A third follow-up study of patients treated before 12 years of age was undertaken in 1990-91. We present longitudinal data on patients treated with BMT when 3-11 (n = 15) and 12-17 (n = 11) years old. No neuropsychological deficits were found in the older group, or among non-irradiated SAA patients. In the first follow-up, children treated with BMT, including TBI at 3-11 years of age, performed less well than donors on tasks involving perceptual and fine-motor speed. In the second follow-up, this group of patients also demonstrated a slight deficit in non-verbal problem solving. An additional relative decline in verbal reasoning was noted in the third follow-up, 5.5-10 years after treatment. Alertness to signs of developmental difficulties in children treated with BMT, including TBI, is recommended.

Adolescent↗

PubMed1995

Identification of volatile metabolites from five fungal species cultivated on two media.

Five fungal species, Aspergillus versicolor, Penicillium commune, Cladosporium cladosporioides, Paecilomyces variotii, and Phialophora fastigiata, were cultivated on two media, malt extract agar and dichloran glycerol agar. Culture flasks provided with inlet and outlet tubes were used and purified, and humidified air was constantly led through the flasks. Air samples from the cultures were sorbed on Tenax GR and analyzed by thermal desorption-gas chromatography. The produced volatile metabolites were analyzed by mass spectrometry. Various hydrocarbons, alcohols, ketones, ethers, esters, sulfur-containing compounds, and terpenes were identified. The most commonly produced substances were 2-methyl-1-propanol, 2-methyl-1-butanol, 3-methyl-1-butanol, 3-methylfuran, and dimethyl disulfide. The production was highly dependent on both medium and species.

Journal Article↗

PubMed1994

An in vivo study of the effect of 5-HT and sympathetic nerves on transferrin and transthyretin mRNA expression in rat choroid plexus and meninges.

Brain expression of transferrin (Tf) and transthyretin (TTR) mRNA has been demonstrated in different species, TTR being found only in the choroid plexus. We report here that both these mRNAs are also expressed in the meninges. In vitro studies have shown that Tf secretion by the rat choroid plexus is stimulated by 5-hydroxytryptamine (5-HT) while sympathetic nerves regulate different transport functions in the same tissue. We have used various in vivo models to study the neuroendocrine regulation of Tf and TTR mRNA expression in the choroid plexus and meninges. Destruction of the serotonergic nerves in the brain by either raphe nuclei lesion or intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT), which both decreased brain 5-HT levels significantly, did not affect Tf or TTR mRNA levels in choroid plexus and meninges, but increased TTR mRNA in liver. Intraventricular injection of 10 or 100 pmol 5-HT did not change the expression of these proteins in any of the tissues studied. Removal of the sympathetic innervation to the choroid plexus by cervical sympathectomy did not affect Tf or TTR mRNA levels in choroid plexus and liver, nor the incorporation of radioactive leucine into protein in various parts of the brain. In conclusion, our results do not support a regulatory role in vivo for neuronally derived 5-HT or sympathetic nerve activity on Tf and TTR mRNA expression in rat choroid plexus and meninges.

5,7-Dihydroxytryptamine↗

PubMed1994

Salivary duct carcinoma--a highly aggressive salivary gland tumour with overexpression of c-erbB-2.

The clinicopathological and immunocytochemical features of nine cases of salivary duct carcinoma are described. This relatively rare tumour, which only recently has been widely recognized as a separate entity, is highly malignant and caused the death in eight of the patients. The tumour cells are arranged in cribriform and solid growth patterns, where the solid tumour nests frequently have comedo necrosis, and a fibrous, often sclerotic, stroma is present. The infiltrating desmoplasmic component and the diffuse invasive growth into adjacent adipose parotid tissue have similarities to ductal breast carcinoma. Immunocytochemical investigation of salivary duct carcinoma showed constant overexpression of c-erbB-2 as detected by membrane accentuation, and high proliferative activity as detected by nuclear positivity for MIB 1 (Ki-67). Changes in the expression of p53 and retinoblastoma gene product do not constitute a constant event in salivary duct carcinoma. A few of the tumours showed scattered cells with distinct nuclear positivity for both progesterone and oestrogen receptors. We emphasize that this highly malignant salivary gland tumour has a characteristic morphology, may not be as rare as previously considered, and that prompt and aggressive therapy is needed.

Adult↗

PubMed1994

Gene expression and secretion of insulin-like growth factor-II and insulin-like growth factor binding protein-2 from cultured sheep choroid plexus epithelial cells.

The gene expression of insulin-like growth factor II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) has previously been demonstrated in rat and human choroid plexus by in situ hybridization analysis. In the present study we have characterized IGF-II and IGFBP-2 transcripts and proteins in primary cultures of epithelial cells from lateral choroid plexus of sheep brain. Northern blot analysis of total RNA showed one major IGF-II mRNA of 4.8 kb and four minor IGF-II transcripts of 1.5, 2.0, 3.0 and 6.0 kb as well as one IGFBP-2 transcript of 1.7 kb. Radioreceptor assay of conditioned medium from the cultured choroid plexus epithelial cells showed inhibition of [125I]IGF-I and [125I]IGF-II binding to mouse NIH 3T3 fibroblasts, the displacement curves being identical to that of unlabelled IGF-II. The conditioned medium was fractionated by gel filtration on a Bio-Gel P-60 column, and analysis by IGF-II radioreceptor assay showed two peaks of IGF-II-binding inhibitory activity of M(r) 7.5-10 and 25 kDa, suggesting the presence of both IGF-II, and an IGFBP. Western immunoblot analysis of conditioned medium with antibodies toward IGF-II and IGFBP-2 demonstrated proteins with M(r) 6 kDa and 32 kDa, respectively. Protein binding assays of the conditioned medium with [125I]IGF-I or [125]IGF-II demonstrated that the IGFBP present in the conditioned medium preferentially binds IGF-II. In conclusion, cultured sheep choroid plexus epithelial cells synthesize and secrete IGF-II and IGFBP-2, suggesting that the choroid plexus epithelium is the main source of these polypeptides in the cerebrospinal fluid.

3T3 Cells↗

PubMed1994

Broadly reactive HIV-2 and SIVmac specific antibody-dependent cellular cytotoxicity in immunized and infected cynomolgus monkeys.

Antibody-dependent cellular cytotoxicity (ADCC) was analysed in groups of cynomolgus monkeys that had been immunized with either HIV-2 (strains SBL6669 or SBL-K135) or SIVmac. HIV-2- and SIVmac-infected monkeys were also studied for ADCC. Sequential serum samples were collected from the animals, which were followed for 1 to 3 years. Sera from the HIV-2-immunized monkeys had ADCC against both homologous and heterologous HIV-2 strains as well as cross-reactivity against SIVmac-infected target cells. This broadly reactive ADCC response could be detected within the first weeks after immunization. Homologous ADCC was also seen in seven of eight SIVmac-immunized monkeys which were all protected from later challenge with SIVmac or SVsm. ADCC titres sometimes decreased after a few months if the immunized monkeys were not boosted whereas most of the HIV-2-and SIVmac-infected monkeys developed a rapid and persistent ADCC response. The presence of ADCC, like the presence of neutralization in previous studies, did not predict whether the immunized monkeys would be protected upon challenge with live virus.

AIDS Vaccines↗