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M Nilsson

Publications and source records attributed to M Nilsson.

At least 19 recordsLinked to original sources
PubMed1999

N-cadherin-mediated adhesion and aberrant catenin expression in anaplastic thyroid-carcinoma cell lines.

The role of cadherins and catenins in the progression of thyroid carcinoma is unclear. We have investigated alpha-, beta- and gamma-catenins and p120(ctn) in relation to the expression of cadherins in human anaplastic thyroid-carcinoma cell lines (HTh7, HTh74, C643 and SW1736) with Western blotting and immunofluorescence. E-cadherin was lacking except in SW1736, which consisted of E-cadherin-positive (approx. 5%) and -negative cells. The alpha- and beta-catenin levels were similar to those of primary cultured non-neoplastic (E-cadherin-positive) human thyrocytes. In contrast, the expression of gamma-catenin was low and variable, correlating with the different levels of cytokeratin in the same cells (HTh74 > SW1736 > C643 > HTh7). p120(ctn) resolved as a doublet in Western blots; the approximately 100-kDa band also found in non-neoplastic epithelial cells was reduced whereas the approximately 115-kDa band, corresponding to the fibroblast-type isoform of p120(ctn), was neo-expressed. A DNA-demethylating agent, 5-aza-2'-deoxycytidine, up-regulated E-cadherin in SW1736 and gamma-catenin in SW1736 and C643, whereas the other cell lines were unresponsive; other catenins were not affected. The catenins were generally distributed along the cell borders. Immunostaining, cell-surface biotinylation and co-immunoprecipitation revealed that all cell lines expressed N-cadherin in connection with beta-catenin at the plasma membrane. Incubation with an N-cadherin antibody disrupted cell-cell adhesion. We conclude that E-cadherin-negative anaplastic thyroid-carcinoma cell lines display functional N-cadherin/beta-catenin complexes, partial or complete loss of gamma-catenin, and isoform shift of p120(ctn). The unequal expression of E-cadherin and gamma-catenin and the variable response to DNA de-methylation suggest that anaplastic thyroid carcinoma is not a uniform entity.

Cadherins↗
PubMed1999

Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory.

The fetal and even the young brain possesses a considerable degree of plasticity. The plasticity and rate of neurogenesis in the adult brain is much less pronounced. The present study was conducted to investigate whether housing conditions affect neurogenesis, learning, and memory in adult rats. Three-month-old rats housed either in isolation or in an enriched environment were injected intraperitoneally with bromodeoxyuridine (BrdU) to detect proliferation among progenitor cells and to follow their fate in the dentate gyrus. The rats were sacrificed either 1 day or 4 weeks after BrdU injections. This experimental paradigm allows for discrimination between proliferative effects and survival effects on the newborn progenitors elicited by different housing conditions. The number of newborn cells in the dentate gyrus was not altered 1 day after BrdU injections. In contrast, the number of surviving progenitors 1 month after BrdU injections was markedly increased in animals housed in an enriched environment. The relative ratio of neurogenesis and gliogenesis was not affected by environmental conditions, as estimated by double-labeling immunofluorescence staining with antibodies against BrdU and either the neuronal marker calbindin D28k or the glial marker GFAp, resulting in a net increase in neurogenesis in animals housed in an enriched environment. Furthermore, we show that adult rats housed in an enriched environment show improved performance in a spatial learning test. The results suggest that environmental cues can enhance neurogenesis in the adult hippocampal region, which is associated with improved spatial memory.

Aging↗
PubMed1999

Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index.

AIMS/HYPOTHESIS: Our aims were to investigate the concentrations and prevalence of autoantibodies against the Mr 65.000 isoform of glutamate decarboxylase (GAD65) and the tyrosine phosphatase-like protein (IA-2) in adults and to test the hypothesis that GAD65 and IA-2 autoantibodies in a regional population are related to abnormal oral glucose tolerance. METHODS: We analysed serum from 2157 Swedish subjects aged either 30, 40, 50 or 60 years old who, in 1988-1992, participated in the Västerbotten County Health Project and were subjected to the World Health Organisation (WHO) standard oral glucose tolerance test at entry into the study. RESULTS: We found 23 of 2157 (1.1%) and 17 of 2152 (0.8%) subjects exceeded the 99th centile of GAD65 autoantibody index and IA-2 autoantibody index, respectively. In 18 subjects with diabetic oral glucose tolerance test, GAD65 autoantibody concentrations were higher than in those with normal oral glucose tolerance test (p = 0.02). Subjects with IGT (n = 185) [corrected] and diabetes (n = 18), i.e. abnormal OGTT (n = 203) [corrected], had higher GAD65Ab [corrected] index compared with those with normal OGTT (p = 0.026) [corrected]. A stepwise multiple logistic regression test showed that the odds ratios for subjects in the highest BMI group to exceed the 95th or 99th GAD65 autoantibody centile were 3.6 (CI 1.4-8.9) and 17.6 (CI 2.6-121.6), respectively. CONCLUSION/INTERPRETATION: GAD65 and IA-2 autoantibodies, are associated with impaired or diabetic glucose tolerance in an adult regional population. This observation together with the association between GAD65 autoantibody concentrations and body mass index indicate a possible relation between islet autoimmunity and beta-cell function abnormalities with obesity and insulin resistance.

Adult↗
PubMed1999

The 5-HT2A receptor antagonist M100907 is more effective in counteracting NMDA antagonist- than dopamine agonist-induced hyperactivity in mice.

The purpose of the present study was to compare the effectiveness of the selective 5-HT2A antagonist M100907 in different psychosis models. The classical neuroleptic haloperidol was used as reference compound. Two hyperdopaminergia and two hypoglutamatergia mouse models were used. Hyperdopaminergia was produced by the DA releaser d-amphetamine or the DA uptake inhibitor GBR 12909. Hypoglutamatergia was produced by the un-competitive NMDA receptor antagonist MK-801 or the competitive NMDA receptor antagonist D-CPPene. M100907 was found to counteract the locomotor stimulant effects of the NMDA receptor antagonists MK-801 and D-CPPene, but spontaneous locomotion, d-amphetamine- and GBR-12909-induced hyperactivity were not significantly affected. Haloperidol, on the other hand, antagonized both NMDA antagonist- and DA agonist-induced hyperactivity, as well as spontaneous locomotion in the highest dose used. Based on the present and previous results we draw the conclusion that 5-HT2A receptor antagonists are particularly effective against behavioural anomalies resulting from hypoglutamatergia of various origins. The clinical implications of our results and conclusions would be that a 5-HT2A receptor antagonist, due to i a the low side effect liability, could be the preferable treatment strategy in various disorders associated with hypoglutamatergia; such conditions might include schizophrenia, childhood autism and dementia disorders.

Amphetamine↗
PubMed1999

Effects of collimator size of a dental X-ray unit on image contrast.

OBJECTIVES: To examine the effect of collimator size on image contrast in dental radiography. METHODS: Two conventional collimators, one circular (53 mm in diameter) and one rectangular (35x45 mm2), were compared with a small rectangular collimator (26x39 mm2). Low-contrast and high-contrast resolution was assessed with the aid of contrast-detail and line-pair phantoms. RESULTS: Shallower holes were observed with the small rectangular collimator. Two-thirds of 17 observers assessing high-contrast resolution considered the small collimator to result in a clearer image than the conventional collimators. The same effect was demonstrated with the line-pair phantom and by microdensitometry. With the small collimator the energy imparted is estimated to be reduced by 54 and 36% compared with the conventional circular and rectangular collimators respectively. CONCLUSIONS: Decrease of the collimator size to fit the film size used for children will result in improved low-contrast and, under some conditions, improved high-contrast resolution. This improvement might have implications for caries diagnosis and monitoring.

Absorptiometry, Photon↗
PubMed1999

A cortisol suppression dose-response comparison of budesonide in controlled ileal release capsules with prednisolone.

AIM: To assess the systemic effect of oral budesonide, given as Entocort controlled ileal release capsules, over a dose range of 3-15 mg/day, compared with that of a moderate dose (20 mg/day) of prednisolone. METHODS: Twenty four healthy subjects were given 3, 9 or 15 mg budesonide or 20 mg prednisolone once daily, or 4.5 mg budesonide b.d., or placebo for 5 days in a randomized, double-blind crossover study. The area under the curve (AUC) of plasma cortisol concentration and the amount of cortisol excreted in the urine were monitored. RESULTS: Both plasma and urine cortisol suppression showed a dose-response for the daily doses of budesonide. Prednisolone, 20 mg, suppressed plasma cortisol (AUC) statistically significantly more than 15 mg budesonide (P = 0.014), and 3 mg budesonide statistically significantly more than placebo (P = 0.010). No difference in AUC was detected between 9 mg and 4.5 mg budesonide b.d. Similar results for budesonide vs. placebo were obtained from urine cortisol excretion data. However, prednisolone affected urine cortisol less than it affected plasma cortisol. CONCLUSION: After 5 days of administration, budesonide controlled ileal release capsules, in both clinical (9 mg/day) and high doses (15 mg/day), affected plasma cortisol less than a moderate (20 mg/day) dose of prednisolone.

Adult↗
PubMed1999

High prevalence of hypophosphataemia amongst patients with infectious diseases. A retrospective study.

OBJECTIVES: To describe the prevalence of hypophosphataemia amongst all patients treated during 1993 for infectious diseases. The associations between serum C-reactive protein, serum albumin and white blood cells in blood were studied amongst hypophosphataemic patients. Comparisons were made according to the severity of infection. DESIGN: A retrospective study of the prevalence of hypophosphataemia, and a case-control study amongst a subgroup of patients. SETTING: The Department of Infectious Diseases, University Hospital, Umeå, Sweden. SUBJECTS: For the prevalence study all 967 patients (449 women and 518 men) treated during 1993 were included. In the case-control study, 108 cases, with serum phosphate < or =0.64 mmol L(-1), 216 age-and sex-matched controls with serum phosphate >0.82 mmol L(-1) (men) and >0.86 mmol L(-1) (women), respectively, were included. RESULTS: In 402 of 967 patients (42%) at least one serum phosphate value was below the reference level. Hypophosphataemia was found in 573 of 1966 blood samples (29%). Severe hypophosphataemia (<0.30 mmol L(-1)) was seen in 1.2% of the patients (0.9% of blood samples). The prevalence of hypophosphataemia was higher amongst women than amongst men. In the case-control study, the serum C-reactive protein and the number of white blood cells was higher amongst the cases compared with the controls (124 vs. 94 mg L(-1) and 11.4 vs. 9.3 cells/L x10(9), respectively). The multiple logistic regression showed a 4-fold higher risk of having low serum phosphate in patients with severe infection, compared with mild infections. None of the other variables (albumin, days of hospital stay or white blood cells in blood) increased the risk for hypophosphataemia. CONCLUSIONS: The high prevalence of low serum phosphate levels and the increased risk of having low levels in severe infections shown in this study needs further attention.

Adolescent↗
PubMed1999

Growth hormone and hexarelin prevent endothelial vasodilator dysfunction in aortic rings of the hypophysectomized rat.

The endothelial vasodilation mechanism(s) has been investigated in aortic rings of hypophysectomized male rats as well as hypophysectomized rats treated for 7 days with growth hormone (GH, 400 microg/kg, s.c.) or hexarelin (80 microg/kg, s.c.). Tissue preparations from intact animals were taken as controls. The results obtained indicate that the release of 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) from aortic rings of hypophysectomized rats was markedly reduced (51%; p<0.01) as compared with that of control preparations; the peak response to cumulative concentration of endothelin-1 (ET-1, from 10(-11) to 10(-5) M) was increased 2.4-fold (p<0.01) versus controls; the relaxant activity of acetylcholine (ACh, from 10(-10) to 10(-4) M) in norepinephrine-precontracted aortic rings was reduced by 39.5+/-4.4%. Pretreatment of hypophysectomized rats with GH or hexarelin markedly antagonized the hyperresponsiveness of the aortic tissue to ET-1 and allowed a consistent recovery of both the relaxant activity of ACh and the generation of 6-keto-PGF1alpha. Collectively these findings support the concept that dysfunction of vascular endothelial cells may be induced by a defective GH function. Because a replacement regimen of GH restored the somatotropic function and increased plasma insulin-like growth factor-I (IGF-I) concentrations in the hypophysectomized rats, it is suggested that IGF-I may have protected the vascular endothelium acting as a biologic mediator of GH action. In contrast to GH, hexarelin replacement neither increased body weight nor affected the plasma concentrations of IGF-I, indicating that its beneficial action on vascular endothelium was divorced from that on somatotropic function and was likely due to activation of specific endothelial receptors.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Rotavirus G-type restriction, persistence, and herd type specificity in Swedish cattle herds.

G-typing of rotavirus strains enables the study of molecular epidemiology and gathering of information to promote disease prevention and control. Rotavirus strains in fecal specimens from neonatal calves in Swedish cattle herds were therefore characterized by using G1 to -4-, G6-, G8-, and G10-specific primers in reverse transcription (RT)-PCR. Fecal samples were collected from one dairy herd (herd A) for 4 consecutive years and from 41 beef and dairy herds (herd B) experiencing calf diarrhea outbreaks. Altogether, 1, 700 samples were analyzed by group A rotavirus enzyme-linked immunosorbent assay, and 98 rotavirus-positive specimens were selected for G-typing by RT-PCR. The effect of herd type, time, geographic region, and clinical symptoms on the G-type distribution was evaluated. Altogether (herds A and B), G10 was found in 59 (60. 2%) fecal specimens, G6 was found in 30 (30.6%) specimens, G3 was found in 1 (1.0%) specimen, and G8 was found in 1 (1.0%) specimen. Seven (7.1%) fecal specimens were not typeable. Herd type specificity in the G-type distribution was demonstrated in the herds in herd B. In the 6 beef suckler herds, only G6 was detected, while rotavirus strains from the 35 dairy herds were predominantly (54%) G10. The G-type distribution was restricted in herds A and B. Twenty-nine of 30 strains from herd A were characterized as G10. In the vast majority of herds in herd B, a single G-type was identified. The serotype G10 and the electropherotype persisted over time in herd A. No characteristic G-type variation in the geographic distribution of cattle herds in herd B was obvious. There was no difference in the G-type distributions between the strains from clinically and subclinically rotavirus-infected calves in dairy herd A. The results from this study strongly indicate a pronounced stability in the rotavirus G-type distribution in Swedish cattle herds, which emphasizes the importance of continuous preventive measures for control of neonatal calf diarrhea. A future bovine rotavirus vaccine in Sweden should contain G10 and G6 strains.

Animals↗
PubMed1999

Functional studies of a fibrinogen binding protein from Staphylococcus epidermidis.

A gene encoding a fibrinogen binding protein from Staphylococcus epidermidis was previously cloned, and the nucleotide sequence was determined. A portion of the gene encompassing the fibrinogen binding domain has now been subcloned in an expression-fusion vector. The fusion protein can bind to fibrinogen in a capture enzyme-linked immunosorbent assay and can be purified by fibrinogen affinity chromatography. This protein can completely inhibit the adherence of S. epidermidis to immobilized fibrinogen, suggesting that the adherence of S. epidermidis to fibrinogen is mainly due to this protein. Antibodies against this fibrinogen binding protein were also found to efficiently block the adherence of S. epidermidis to immobilized fibrinogen. Despite homology with clumping factors A and B from S. aureus (cell surface-associated proteins binding to fibrinogen), binding involved the beta chain of fibrinogen rather than the gamma chain, as in clumping factor A.

Animals↗
PubMed1999

Viral diarrhea in children in Beijing, China.

A study was undertaken from November 1994 to August 1996 to determine the role of viruses in children (< or =5 years of age) hospitalized at Beijing Children Hospital, Beijing China, for acute diarrhea. Stool samples from diarrheal patients were investigated by ELISA, electron microscopy, and RT-PCR for the presence of rotavirus, calicivirus, astrovirus, and adenovirus. Group A rotavirus was detected in 55.9% of all diarrheal patients and comprised 82.5% of all viruses detected. Group A rotavirus samples were further characterized for their G-type specificity by RT-PCR. Four major G types (1-4) were identified. G1 to G4 accounted for 58.9%, 15.7%, 16.8%, and 6.3%, respectively, of the serotyped samples. Almost all rotavirus infections occurred in children less than 1 year of age, with a significant clustering during the winter months. Group C rotavirus was detected in one 18-month-old child. Astroviruses, caliciviruses, and adenoviruses were detected in 8.5%, 7.6%, and 2.5% of the hospitalized children, respectively. This, the first viral etiological study of childhood diarrhea in China, concludes that rotavirus G1-4 strains play an important role in severe diarrhea in Beijing children.

Adenoviridae↗
PubMed1999

Cyclosporin A-sensitive changes in mitochondrial glutathione are an early response to intrastiatal NMDA or forebrain ischemia in rats.

An intrastriatal injection of NMDA produced an increase in glutathione to 152% of control values in mitochondria isolated from striatum at 1 h later. Total tissue glutathione was not changed. The mitochondrial increase was largely reversed by 2 h. Glutathione content was not significantly affected in mitochondria from a part of the cerebral cortex that did not exhibit damage following intrastriatal NMDA. Glutathione was similarly increased in mitochondria from both cortex and striatum at 1 h after a short period of forebrain ischemia, confirming our previous findings. The increases in mitochondrial glutathione developed shortly after accumulations of mitochondrial calcium that have been observed previously. Intravenous injection of cyclosporin A immediately following either the NMDA treatment or reversal of the ischemic period partially inhibited the increases in glutathione in mitochondria from the affected brain subregions. These studies provide evidence that early changes sensitive to cyclosporin A develop in mitochondria under pathological conditions in the intact brain. These glutathione increases are consistent with an induction of the mitochondrial permeability transition in the affected tissue.

Animals↗
PubMed1998

Signal amplification of padlock probes by rolling circle replication.

Circularizing oligonucleotide probes (padlock probes) have the potential to detect sets of gene sequences with high specificity and excellent selectivity for sequence variants, but sensitivity of detection has been limiting. By using a rolling circle replication (RCR) mechanism, circularized but not unreacted probes can yield a powerful signal amplification. We demonstrate here that in order for the reaction to proceed efficiently, the probes must be released from the topological link that forms with target molecules upon hybridization and ligation. If the target strand has a nearby free 3' end, then the probe-target hybrids can be displaced by the polymerase used for replication. The displaced probe can then slip off the targetstrand and a rolling circle amplification is initiated. Alternatively, the target sequence itself can prime an RCR after its non-base paired 3' end has been removed by exonucleolytic activity. We found the Phi29 DNA polymerase to be superior to the Klenow fragment in displacing the target DNA strand, and it maintained the polymerization reaction for at least 12 h, yielding an extension product that represents several thousand-fold the length of the padlock probe.

Base Sequence↗
PubMed1998

Alterations in the biosynthesis of cholesterol, dolichol and dolichyl-P in the genetic cholesterol homeostasis disorder, Niemann-Pick type C disease.

The biosynthesis of cholesterol, dolichol and dolichyl-P were investigated in a murine model of Niemann-Pick type C disease using both in vitro and in vivo systems. In vivo incorporation of [3H]mevalonate into squalene, dolichol and dolichyl-P decreased. The amount of dolichyl-P was elevated due to a decrease in the rate of degradation. Labeling of squalene and cholesterol of liver homogenates in vitro was decreased in the diseased mice and a lowering of microsomal activities of both HMG-CoA reductase and squalene synthase were also observed. In experiments with brain homogenate, decreased [3H]mevalonate labeling of squalene, cholesterol and dolichol was found in vitro. The decreases in cis-prenyltransferase and squalene synthase activities were observed at a very early phase of the disease. In contrast to the decreased biosynthesis of cholesterol observed in vitro, the labeling of total liver cholesterol was found to be increased in Niemann-Pick type C liver upon in vivo investigation, possibly due to the accumulation of this lipid as a result of a deficient transport process. In the brain, where in vivo labeling reflects only biosynthesis, a decreased rate of cholesterol synthesis was demonstrated.

Animals↗
PubMed1998

Modulation of mechanically induced calcium waves in hippocampal astroglial cells. Inhibitory effects of alpha 1-adrenergic stimulation.

The effects of different adrenoceptor agonists were investigated on mechanically induced Ca2+ waves in astroglial cells in astroglial-neuronal mixed cultures from rat hippocampus. In the initial part of the study some properties of the waves were characterized. The results show that the initiation of the Ca2+ waves was not critically dependent on extracellular Ca2+ but both the calcium signal and the propagation area of the calcium wave were significantly reduced when the experiments were performed in Ca2+-free buffer. In addition, using the phospholipase C (PLC) inhibitor U-73122 (1 microM) and the gap junction uncoupler octanol (1 mM), the results showed that the Ca2+ wave propagation required PLC activation and functional gap junctions. Further, the data also showed that the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA 150 nM) reduced the spreading of the waves. The adrenoceptor agonists isoproterenol (iso; beta), phenylephrine (phe; alpha1) and clonidine (clon; alpha2) were evaluated for their short-term (<30 s) effects on the wave propagation. The propagation area was persistently decreased 1, 3 and 5 min after removal of phe. No effects were observed after incubation with iso or clon. Furthermore, using U-73122 or PMA together with phe, shortly incubated, the experiments showed that PLC was a central regulator in the initial phase of the initiation procedure of wave propagation. However, under these conditions PKC was shown not to be involved. Instead it appeared that PKC exerted its inhibitory action on the Ca2+ waves in a latter phase, after prolonged phe exposure. Taken together, the results show that the propagation of Ca2+ waves between astroglial cells in primary cultures can be inhibited/regulated in two principally different ways which involve a pronounced time component. The results also further point out the adrenergic signaling system as an important mediator of dynamic neuron-astroglial information exchange.

1-Octanol↗
PubMed1998

Regulation of the glial glutamate transporter GLT-1 by glutamate and delta-opioid receptor stimulation.

The excitatory effect of presynaptically released glutamate is tightly regulated and terminated by high affinity sodium-dependent glutamate transporters. The regulation of the glial glutamate transporter GLT-1 is potentially important in synaptic modulation. Using astroglial cultures prepared from the rat cerebral cortex, we found that the delta-opioid receptor agonist [D-pen2,D-pen5]-enkephalin decreases and glutamate increases the expression of the GLT-1 transporter mRNA. Corresponding changes in the uptake kinetics were found after incubation for 48 h with the respective agonists when glial glutamate uptake was measured in primary astroglial cultures. The data suggest that long-term receptor activation induces alterations in glial glutamate uptake properties.

ATP-Binding Cassette Transporters↗
PubMed1998

Assembly of viroplasm and virus-like particles of rotavirus by a Semliki Forest virus replicon.

In this study we have used an expression system based on Semliki Forest virus (SFV) to study assembly and intracellular localization of certain capsid proteins of rotavirus in neurons and mammalian epithelial cells. The complete genes of vp2 (vp2A) and vp6 (vp6A) of group A rotavirus (SA-11) and gene 5 encoding vp6 (vp6C) of porcine group C rotavirus (strain Cowden/AmC-1) were inserted into an SFV expression replicon. Transfection of BHK-21 cells with in vitro-made SFV transcripts resulted in a high level of expression of the heterologous genes. Cotransfection with helper RNA encoding the SFV structural proteins, but lacking the genomic RNA packing signal, resulted in production of recombinant infectious virus. Immunological and biochemical analysis revealed that vp6 was expressed to high levels in primary neurons and mammalian epithelial cells and that vp6 was retained as an authentic homotrimer, stabilized by noncovalent interactions with native antigenic determinants. Thin section electron microscopy analysis revealed that vp6 alone assembled into viroplasm-like structures in the cytoplasm. While coexpression of vp2 and vp6 of group A rotavirus resulted in formation of single-shelled-like particles, no evidence of intracellular assembly was found, suggesting that other viral proteins are required for intracellular formation of single-shelled particles. A notable observation was that the vp6 proteins of group A and C rotaviruses showed different immunofluorescence patterns in BHK-21 cells; vp6C displayed an intense punctate immunofluorescence pattern, while vp6A was characterized by a pronounced filamentous staining in close vicinity to the cytoskeleton.

Animals↗