Search PubMed⌕ Search

Biomedical subjects

M Nilsson

Publications and source records attributed to M Nilsson.

At least 109 records · Page 6Linked to original sources
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

Human neutrophil lipocalin, a highly specific marker for acute exacerbation in cystic fibrosis.

Cystic fibrosis (CF) is characterized by the production of abnormally thick secretions in the airways, chronic bacterial endobronchial infections and a chronic, predominantly neutrophilic inflammatory response. Therefore, myeloperoxidase (MPO) and lactoferrin are frequently used as inflammatory markers. Recently, a new protein in the neutrophil granules, human neutrophil lipocalin (HNL) has been discovered. The aim of the present study was to investigate HNL in sera of patients with CF and its relation to MPO and lactoferrin as well as to acute pulmonary exacerbation. Serum concentrations of HNL, MPO and lactoferrin were determined in 42 patients with CF and in 25 healthy subjects. Patients with CF were divided into groups with and without acute pulmonary exacerbation (APE) and also with and without colonization with Pseudomonas aeruginosa (Pa). Median serum levels of HNL (200.5 microg x L(-1)), MPO (595 microg x L(-1)) and lactoferrin (1,356.5 microg x L(-1)) were significantly increased in patients with CF compared to control subjects (57.7, 178 and 478 microg x L(-1), respectively; p<0.0001). CF patients with APE had significantly increased serum concentrations of HNL (321 versus 97.7 microg x L(-1); p<0.0001), MPO (1,125 versus 300 microg x L(-1); p<0.005) and lactoferrin (4,936 versus 980 microg x L(-1); p<0.001) compared with patients in stable clinical condition. Similarly, patients colonized with Pa had significantly higher concentrations of HNL, MPO and lactoferrin than Pa negative patients. These results indicate that in patients with cystic fibrosis, serum concentrations of human neutrophil lipocalin are markedly increased with a strong relationship to myeloperoxidase and lactoferrin. Thus, determination of serum human neutrophil lipocalin concentrations may be another useful diagnostic tool to monitor neutrophil inflammation in cystic fibrosis. The more marked difference in human neutrophil lipocalin compared with myeloperoxidase concentrations with no overlap between patients with acute pulmonary exacerbation and those in stable condition even suggests that human neutrophil lipocalin may be a more sensitive and specific discriminator.

Acute-Phase Proteins↗
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↗
PubMed1998

Stimulation of 5-HT2A receptors on astrocytes in primary culture opens voltage-independent Ca2+ channels.

Mechanisms underlying the 5-HT2A receptor induction of intracellular Ca2+ mobilization and Ca2+ influx in type I astroglial cells in primary culture from newborn rat cerebral cortex were evaluated. The 5-HT-evoked Ca(2+)-transients, inhibited by the 5-HT2A antagonists ketanserin or 4-(4-fluorobenzoyl)-1-(4-phenylbutyl) piperidine oxalate, consisted of an initial peak caused by inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release from internal stores, and a second sustained part which was due to Ca2+ transport over the plasma membrane. The responses were pertussis toxin-insensitive, suppressed by the phospholipase C inhibitor neomycin and were inhibited by the Ca(2+)-ATPase inhibitor thapsigargin. Furthermore, the responses were inhibited by the IP3 receptor antagonist heparin. When the second sustained part of the 5-HT-evoked response was studied, it was concluded that Ca2+ influx was not a result of opening of voltage operated calcium channels of either L, N or T-type. Instead it appeared that Ca2+ entered the cells through specialized voltage independent Ca2+ channels which were dependent of the IP3 production and subsequent Ca2+ release from internal stores. From this, we conclude that 5-HT opens Ca2+ channels in astrocytes which closely resemble depletion-operated Ca2+ channels (DOCCs).

Animals↗
PubMed1998

Pharmacokinetics of bambuterol in healthy subjects.

AIMS: To study the pharmacokinetics and bioavailability of the prodrug bambuterol and its bronchodilator moiety terbutaline in healthy subjects. METHODS: Eight healthy subjects (four women) received intravenous doses of bambuterol and terbutaline. On a third occasion, they, plus another four subjects, ingested oral bambuterol as a single dose followed by repeated doses once daily for 7 days. Plasma concentrations and urinary excretion of bambuterol and terbutaline were measured. RESULTS: After intravenous administration, renal clearances of bambuterol and terbutaline were similar (about 140 ml min(-1)), but there was a five-fold difference in total clearance (bambuterol 1.25 l min(-1), terbutaline 0.23 l min(-1)). Volume of distribution (Vss) was 1.6 l kg(-1) b.w. for both substances. A similar renal clearance of bambuterol was found during oral administration but that of terbutaline decreased (to about 120 ml min(-1)). Mean terminal half-life of bambuterol was 2.6 h after intravenous and 12 h after oral administration, implying that uptake was rate-limiting. Mean residence time of terbutaline generated from oral bambuterol was 34 h compared with 8.0 h when terbutaline as such was infused. Generated terbutaline had a bioavailability of 36% (28-46) after intravenous and 10.2% (6.1-13.2) after oral administration of the prodrug. Bambuterol was well tolerated. The mean activity of plasma cholinesterase, an enzyme catalyzing bambuterol metabolism, was inhibited between 30-60% during repeated oral dosing. It virtually regained original activity within 48 h after the last dose. CONCLUSIONS: The plasma concentration ofterbutaline fluctuated little during repeated oral administration (mean peak: trough ratio 1.9), as a result of prolonged absorption of bambuterol and slow formation of terbutaline. Thus, the pharmacokinetic properties of bambuterol make it suitable for oral once-daily dosage.

Administration, Oral↗
PubMed1998

Serum eosinophil cationic protein, eosinophil protein X and eosinophil peroxidase in relation to pulmonary function in cystic fibrosis.

BACKGROUND: Recently, increased serum levels of eosinophil cationic protein (ECP) in cystic fibrosis (CF) have been reported which were closely related to the levels in sputum. In the present study we investigated other eosinophil proteins such as eosinophil peroxidase (EPO) and eosinophil protein X (EPX) in sera of patients with CF and their relation to pulmonary function. METHODS: Serum samples from 42 patients with CF and from 25 healthy control subjects were measured for ECP, EPO and EPX. Lung function tests were performed by using whole body plethysmographic technique, and the results were correlated with the levels of eosinophil granule proteins. RESULTS: Serum ECP (median: 20.9 microg/L), EPO (median: 30.3 microg/L) and EPX (median: 37.9 microg/L) levels were significantly increased in CF compared with healthy controls (3.5 microg/L, P < 0.0001, 5.6 microg/L, P < 0.0001 and 14.6 microg/L, P < 0.0001, respectively) whereas eosinophil counts were not different. There was a strong correlation between the levels of eosinophil proteins and variables of pulmonary function, like between ECP and forced vital capacity (r = -0.764, P < 0.0001). In addition, ECP concentrations were significantly related to the levels of EPO and EPX, albeit, in some patients with low ECP levels, increased EPO and EPX concentrations were observed. CONCLUSION: These results indicate that in patients with CF, ECP, EPO and EPX concentrations also were increased with a significant relationship between these three eosinophil proteins. Since eosinophil activity in patients with CF is strongly correlated with pulmonary function, the assessment of eosinophil granule proteins might be useful for clinical monitoring in CF.

Adolescent↗
PubMed1998

Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6.

A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive to GHRH and GHRP-6 as well as octreotide.

Acromegaly↗