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Biomedical subjects

A Nilsson

Publications and source records attributed to A Nilsson.

At least 145 records · Page 8Linked to original sources
PubMed1998

Proximal tubular function in adult rats treated neonatally with enalapril.

Neonatal treatment with angiotensin-converting enzyme (ACE) inhibitors or the angiotensin II type-1 receptor antagonist losartan in rats induces irreversible renal histological abnormalities, mainly papillary atrophy, in association with an impairment in urinary concentrating ability. The aim of the present study was to assess proximal tubular function in adult rats treated neonatally with enalapril. Male Wistar rats received daily, intraperitoneal injections of either enalapril (10 mg kg-1) or isotonic saline vehicle from 3 to 24 days of age. In 15-week-old, hydropenic rats we analysed: (i) proximal tubular iso-osmotic fluid reabsorption using the method of lithium clearance; and (ii) maximal tubular D-glucose reabsorption (TmG), under pentobarbital anaesthesia. The main findings were that neonatally enalapril-treated rats showed: (i) reductions in absolute (APRH2O) and fractional (FPRH2O) iso-osmotic fluid reabsorption in the proximal tubules (APRH2O: 0.50 +/- 0.02 vs. 0.64 +/- 0.03 mL min-1 g KW-1, P < 0.05; FPRH2O: 58 +/- 3 vs. 68 +/- 2%, P < 0.05); and (ii) a normal TmG. In addition, during baseline clearance measurements neonatally enalapril-treated rats showed increases in urine volume and fractional excretion rates of sodium and potassium, a reduction in urine osmolality, whereas glomerular filtration rate and effective renal plasma flow were unaltered. These results suggest that neonatal ACE inhibition produces an irreversible, but differentiated, abnormality in proximal tubular function. Thus, the development of a normal proximal tubular function in the rat seems to be dependent on an intact renin-angiotensin system, (RAS) neonatally.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Sphingomyelin, glycosphingolipids and ceramide signalling in cells exposed to P-fimbriated Escherichia coli.

Uropathogenic Escherichia coli attach to epithelial cells through P fimbriae that bind Galalpha1-4Galbeta-oligosaccharide sequences in cell surface glycosphingolipids. The binding of P-fimbriated E. coli to uroepithelial cells causes the release of ceramide, activation of the ceramide signalling pathway and a cytokine response in the epithelial cells. The present study examined the molecular source of ceramide in human kidney A498 cells exposed to P-fimbriated E. coli. Agonists such as TNF-alpha and IL-1beta released ceramide from sphingomyelin by the activation of endogenous sphingomyelinases and hydrolysis of sphingomyelin, and triggered an IL-6 response. P-fimbriated E. coli caused a slight increase in endogenous sphingomyelinase activity, but there was no associated sphingomyelin hydrolysis. Instead, the concentration of galactose-containing glycolipids decreased. We propose that P-fimbriated E. coli differ from other activators of the ceramide pathway, in that release of ceramide is from receptor glycolipids and not from sphingomyelin. Receptor breakdown may be an efficient host defence strategy, as it reduces the concentration of cell surface receptors, releases soluble receptor analogues and activates an inflammatory response.

Ceramides↗
PubMed1998

Detection of Yersinia enterocolitica in food by PCR amplification.

A polymerase chain reaction (PCR) assay was developed for detection of pathogenic, virulent strains of Yersinia enterocolitica. By using both virulence loci virF and ail as markers for pathogenicity, detection of species with a virulence factor present was possible. DNA preparation in the presence of hexadecyl trimethy ammonium bromide (CTAB) was followed by two 44 cycle amplification reactions, one for each of the markers. As few as 10(2) Y. enterocolitica cells were detected in ground pork in the presence of 10(5)-10(6) bacteria of other species. The described PCR assay provides a sensitive robust assay for the detection of virulent Y. enterocolitica in food.

Food Microbiology↗
PubMed1998

Colour Doppler imaging of shunts from the left portal branch in portal hypertension. Description of a typical pattern.

PURPOSE: To describe the typical colour Doppler appearance of a shunt through the parenchyma of the left lobe of the liver in portal hypertension. MATERIAL AND METHODS: Ultrasound images of 141 patients with biopsy-verified cirrhosis were reviewed. Special note was taken of the appearance of shunts from the left portal branch. RESULTS: In 28 patients, shunts from the left portal branch were detected ultrasonographically, 10 of which ran through the liver parenchyma on a course separated from the ligamentum teres. Seven of these 10 followed a tortuous course just below the surface of the liver creating a ball or corkscrew-like pattern. CONCLUSION: Shunts from the left portal branch are not uncommon and may represent the only ultrasonographically detectable pathology in these patients. Recognition of the typical pattern will facilitate their detection.

Biopsy↗
PubMed1998

Orally fed digalactosyldiacylglycerol is degraded during absorption in intact and lymphatic duct cannulated rats.

Membrane lipids of green plants digalactosyldiacylglycerol (DGalDG) and monogalactosyldiacylglycerol (MGalDG) are hydrolyzed in vitro by human duodenal contents, pancreatic juice and bile salt stimulated lipase and guinea pig and rat pancreatic lipase-related protein 2 to free fatty acids, di- and monogalactosylmonoacylglycerols and water soluble galactose-containing compounds. The fate of intermediate products is unknown. We have investigated the digestion and absorption of DGalDG in rats. [3H]- and [14C]-labeled DGalDG in galactolipid dispersions, and 200 g/L soybean triacylglycerol (TG) oil-galactolipid emulsions of different concentrations were fed orally to intact and lymphatic duct cannulated rats. Chyle, gastrointestinal tract, liver and plasma were analyzed for radioactivity in different lipid classes. Recovery of [3H] also was determined in feces. Comparison was made with an emulsion of [14C]dipalmitoyl-phosphatidylcholine ([14C]DPPC), soybean TG oil and soybean phosphatidylcholine (PC). Less than 2% of the radioactivity in chyle was found in DGalDG, >70% of the radioactivity in triacylglycerol (TG), and the remaining part in glycerophospholipids. In intact rats, <1.5% of radioactivity in liver and plasma was identified as DGalDG. In experiments where 120 mg galactolipid-phospholipid mixture or 120 mg PC were given in a soybean TG oil-emulsion, the absorption of galactolipid fatty acids was less complete than PC-fatty acids, as indicated by analysis of feces and intestinal contents. Galactolipids are not absorbed intact or as reacylated monoacyl compounds by rats.

Administration, Oral↗
PubMed1998

Production of T-cell cytokines at the single-cell level in patients with inflammatory arthritides: enhanced activity in synovial fluid compared to blood.

We used a newly developed, sensitive ELISPOT technique in order to estimate the number of cells producing interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) in patients with rheumatoid arthritis (RA) and other inflammatory arthritides, and to correlate the results with clinical and laboratory parameters of disease activity. SFMC and PBMC were cultured either without stimuli or with a standardized dose of phytohaemagglutinin (PHA) for 6 h. Twenty-nine patients, 16 with RA and 13 with other inflammatory joint diseases, were investigated and compared to PBMC from 25 healthy controls. The mean number of IFN-gamma-producing cells was 37.1/10(5) plated SFMC (range 0-121.5). The corresponding value for PBMC was 5.1 (0-39). The difference was highly significant (P = 0.0033 for RA patients, P = 0.0050 for non-RA patients and P < 0.0001 for all patients). Forty-five per cent of SFMC samples (range for all samples 0-38.5 SFC/10(5) MNC) and 25% of PBMC samples (0-20.5) exhibited spontaneous IL-4 production, yielding a significant difference for all patients treated collectively (P = 0.021). Although the cells that spontaneously secrete these cytokines are relatively few, quantification of these cells thus shows increased functional T-cell activation and decreased ratio of cells spontaneously producing IL-4 vs IFN-gamma in the joint fluid as compared to blood of arthritis patients.

Adult↗
PubMed1998

Digestion of ceramide by human milk bile salt-stimulated lipase.

BACKGROUND: There is a renewed interest in metabolism of sphingolipids because of their role in signal transduction. Sphingomyelin is the dominating phospholipid in human milk but its metabolism and possible function in the gastrointestinal tract of breast fed infants is unknown. We explored whether bile salt-stimulated milk lipase has a role in sphingolipid metabolism. METHODS: In vitro assays of sphingomyelinase and ceramidase activities, using radiolabeled substrates, human milk samples and purified native and recombinant variants of bile salt-stimulated milk lipase with or without known activators or inhibitors. RESULTS: Human whey and purified lipase catalysed hydrolysis of palmitoyl-labeled ceramide with the highest rate around pH 8.5-9.0. 1 mg of lipase hydrolysed 0.7 micromol ceramide in one hour at pH 8.5 in presence of 4 mM bile salt. The activity of whey was inhibited by antibodies towards human bile salt-stimulated milk lipase, indicating that this lipase accounted for virtually all ceramidase activity in the milk. In contrast, bile salt-stimulated milk lipase showed no activity against sphingomyelin. However we give evidence of a separate, hitherto unknown, acid sphingomyelinase in human milk. Under the used in vitro conditions this sphingomyelinase could account for hydrolysis of half of milk sphingomyelin in one hour. CONCLUSIONS: Human milk bile salt-stimulated milk lipase hydrolyses ceramide and may thus have a role in sphingomyelin digestion, but only after initial hydrolysis to ceramide and phosphorylcholine. Part of the latter could be carried out in the stomach by the acid milk sphingomyelinase now described. We speculate that these two milk enzymes may be of importance for optimal use of human milk sphingolipids.

Amidohydrolases↗
PubMed1998

Therapy-resistant periodontitis. Psychosocial characteristics.

This study investigated the perspective of a stress system disorder in the pathogenesis of therapy-resistant periodontitis. The goal was to find indications that the stress-behaviour-immune system model holds as an explanatory model for the understanding of periodontal disease. 2 patient-groups were compared: one group classified as responding well to periodontal treatment (responsive-group, R-group, n=11); the other group was classified as responding less well to treatment (non-responsive-group, NR-group, n=11). Somatic and psychological factors were described as obtained by interviews and psychological testings. These findings were related to clinical data documented during the treatment of the patients. An exact logistic multivariate regression analysis was performed on a model based on variables selected by bivariate analysis (variable versus group). The results indicated that the NR-group patients displayed indications of more psychosocial strain and a more passive-dependent personality. The R-group patients displayed a more rigid personality and possibly a less stressful psychosocial situation in the past. The report highlights the possible contribution of stress factors in the context of therapy resistant periodontal disease, and the results seem to be understandable within the context of a stress system disorder perspective.

Adult↗
PubMed1998

Association of vitamin K-dependent coagulation proteins and C4b binding protein with triglyceride-rich lipoproteins of human plasma.

The triglyceride (TG) concentration in plasma is an independent risk factor for coronary heart disease. There is evidence that TG-rich lipoprotein (TGRLP), ie, chylomicrons (CMs), chylomicron remnants (CMRs), and VLDLs associate with factor VII and prothrombin and that the association enhances a platelet factor Xa-mediated prothrombin activation when the CM-prothrombin complex is exposed to platelets. In this study, we examined the association of the vitamin K-dependent coagulation factors VII, IX, X, and prothrombin, as well as the anticoagulation protein C and its cofactor protein S, in plasma lipoproteins obtained from human fasting and postprandial plasma. We also analyzed some other proteins that are related to the coagulation system but not to vitamin K-dependent proteins, including factor V, serum amyloid P component (SAP), C4b binding protein (C4BP), and thrombomodulin (TM), and as a control, Ig G. Human TGRLP (d < 1.006 kg/L), LDL (d = 1.006 to 1.063 kg/L), and HDL (d = 1.063 to 1.210 kg/L) were separated from normal subjects both in fasting and 2 to 3 hours after the ingestion of a meal containing 100 g fat. The different coagulation proteins, SAP, C4BP, TM, and Ig G were determined by SDS-polyacrylamide gel electrophoresis combined with Western blotting, using specific polyclonal or monoclonal antibodies, and were visualized by peroxidase staining. All the vitamin K-dependent proteins associate with TGRLP in both fasting and postprandial plasma, but not with LDL or HDL. Factor V, SAP, TM, and Ig G were not found in any lipoprotein classes. C4BP, which is a regulatory protein of the classic pathway of the complement system and which binds protein S in vivo to regulate blood coagulation, was present in TGRLP, especially postprandial, but not in LDL or HDL. The amounts of prothrombin, protein S, and C4BP in postprandial TGRLP were larger than those in fasting TGRLP. Vitamin K-dependent procoagulation and anticoagulation proteins, as well as C4BP, could be associated with TGRLP in vivo. If the association enhances prothrombin activation, this effect may thus be counteracted by simultaneous binding of protein S.

Adult↗
PubMed1998

Creating their own private and public: the male homosexual life space in a Nordic city during high modernity.

In this article I describe the male homosexual life space in a Nordic city during the decades around the Second World War. It consisted almost entirely of outdoor places such as parks, public conveniencies, and streets. It included, in Delph's (1978) words, not only erotic, but also cultural and social oases, fostering an extensive and varied social life and a growing community. Most of this outdoor space was invisible to those other than the participants. It had its own differentiation of, and meanings for, "public" and "private." A poor economy, overcrowding, and the classical modern city helped shape the location and design of the male homosexual life space, as did the participation of many men who did not look upon themselves as "homosexual." During this period, and especially after the Second World War, this life space began to change in a direction pointing towards that of today, that is, towards less outdoor life and more life in homes and semipublic indoor spaces. Better economy, the rise of the welfare state, and diminished overcrowding furthered this movement. Among other things, these changes stimulated the withdrawal of men who did not see themselves as "homosexual." The transformation of the city into the spread out, suburbanized city, with segregation of various functions, contributed to the development, as did the obstruction of parks and toilets as meeting places by public authorities. The law reform of 1944, which decriminalized homosexual erotic acts between adults, was also of importance.

Adolescent↗
PubMed1998

Cortisol increases growth hormone-receptor expression in human osteoblast-like cells.

It is well known that high levels of glucocorticoids cause osteoporosis and that physiologic levels of growth hormone (GH) are required for normal bone remodeling. It has been suggested that glucocorticoids regulate GH-responses via the regulation of GH-receptor expression. The aim of the present study was to investigate whether cortisol plays a role in the regulation of GH-receptor expression in cultured human osteoblasts. The effect of serum starvation and cortisol on GH-receptor expression was tested in human osteoblast (hOB)-like cells. Serum starvation for 24 h resulted in an increase in GH-receptor mRNA levels (90 +/- 1% over control culture). Cortisol increased GH-receptor mRNA levels in a dose-dependent manner with a maximal effect at 10(-6)M. The stimulating effect of cortisol on GH-receptor mRNA levels was time-dependent, reaching a peak 12 h after the addition of cortisol (126 +/- 29% over control culture) and remaining up to 12 h later. The increase in GH-receptor mRNA levels was accompanied by an increase in 125I-GH binding which reached a maximum at 24 h (196 +/- 87% over control culture). In conclusion, glucocorticoids increase GH-receptor expression in hOB-like cells. Further studies are needed to clarify whether glucocorticoid-induced regulation of the GH-receptor is important in human bone physiology.

Adolescent↗
PubMed1998

Color Doppler energy: detection of hypoperfused areas in renal transplants.

The aim of this study was to determine if an area of decreased color on color Doppler energy scans in a transplanted kidney could be related to significant pathologic conditions. Three hundred and ninety-eight scans in 150 patients were thus evaluated prospectively, and 12 such areas were found and correlated to B-mode, spectral, and color Doppler sonography as well as clinical and laboratory findings. A cause for the hypoperfused area was found in all cases; causes included two cases of focal infection, four arteriovenous fistulas, one kinking of an artery, and five perioperatively severed accessory arteries. We conclude that a color Doppler energy evaluation of perfusion differences can be used to detect pathologic lesions in a transplanted kidney.

Humans↗
PubMed1998

Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes.

Melagatran, a new, competitive and rapid inhibitor of thrombin with a molecular mass of 429 Da is described. Melagatran is well tolerated when administered in very high doses, and the oral bioavailability in the dog is relatively high. The aim of the study was to determine, in the preclinical setting, the degree of selectivity against the fibrinolytic system required for entering the clinical development phase. Melagatran was compared with two structurally similar thrombin inhibitors, inogatran and H 317/86. The potent inhibition of thrombin by melagatran was demonstrated by a low inhibition constant (Ki) for thrombin (0.002 micromol/l) and prolongation of clotting time to twice the control value in coagulation assays at low concentrations (0.010, 0.59 and 2.2 micromol/l for thrombin time, activated partial thromboplastin time and prothrombin time, respectively). Furthermore, thrombin-induced platelet aggregation was inhibited at the same concentration (IC50-value 0.002 micromol/l) as the Ki-value for thrombin. In two assays of global fibrinolysis, inhibition was observed at a concentration of 1.1 micromol/l in a euglobulin plasma fraction model, while no inhibition was observed at a concentration of < or = 10 micromol/l in a plasma model. In an in vivo model of endogenous fibrinolysis in the rat, inhibition of fibrinolysis was observed at > or = 1.0 micromol/l. In all assays, except the Ki-ratio determinations, the compounds could be graded with regard to selectivity against the fibrinolytic system: inogatran > melagatran > H 317/86. For melagatran, inhibition of fibrinolysis was not observed at concentrations below the upper limit of the proposed therapeutic plasma concentration interval (< 0.5 micromol/l). Thus, melagatran seems to have a sufficient selectivity against the fibrinolytic system, while H 317/86 was considered to be insufficient for clinical development.

Administration, Oral↗
PubMed1997

Tissue uptake and interconversion of plasma unesterified 14C linoleic acid in the guinea pig.

Part of the arachidonic acid (20:4, n - 6) pools in the gastrointestinal tract and blood forming tissues may be formed by local interconversion of linoleic acid (18:2, n - 6) taken up as a free fatty acid from blood. This study examined the rate of uptake and interconversion of unesterified 14C-18:2 by different tissues in young guinea pigs. The clearance rate of 14C-18:2 was fast, and the initial half-life was 6.3 s. The retention of 14C in tissue lipids was 1.6-1.8% g-1 in the liver, 0.4% g-1 in stomach, 0.7% g-1 in small intestine, 0.2% g-1 in colon, 0.4% g-1 in bone marrow and 0.7% g-1 in spleen. Autoradiographic localization of 3H-18:2 under light microscope demonstrated that most of the 3H radioactivity of the gastrointestinal tract was in the mucosa, in both villus and crypt cells. In bone marrow smears, a high density of silver grains was found in megakaryocytes. The percent of 14C in delta6 desaturase products was higher in gastrointestinal tract, heart, lung, bone marrow and spleen than in liver. The ratio of 14C-20:3/14C-20:4 formation in most tissues was high, and a notable finding being a lower rate of 20:4 formation from plasma free 18:2 in the liver, (170 pmol min-1) than in the gastrointestinal tract (428 pmol min-1) and bone marrow (1203 pmol min-1). The local interconversion of 18:2 into delta6 desaturase products is thus an important source of 20:4 in these organs in guinea pigs.

Animals↗
PubMed1997

Serotonin as a regulator of hypothalamic-pituitary-interrenal activity in teleost fish.

Evidence for the presence of a serotonin1A (5-HT1A) receptor subtype in the salmonid fish brain has recently been presented. In the present study the potent 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) was tested for its effect on plasma cortisol concentrations in rainbow trout (Oncorhynchus mykiss). Blood was sampled and 8-OH-DPAT administered through a catheter in the dorsal aorta. Thirty minutes after the injection of 40 microg of 8-OH-DPAT/kg, plasma cortisol levels had increased from 12 to 149 ng/ml, whereupon they fell, reaching baseline levels after 4 h. The effect of 1-40 microg 8-OH-DPAT/kg on plasma cortisol concentrations was dose-dependent. The results lends further support to the hypothesis that the brain serotonergic system plays a key role in integrating autonomic, behavioral and neuroendocrine stress-responses in fish as well as mammals, suggesting that not only the structural and biochemical organization, but also the function of the serotonergic system has been conserved during vertebrate evolution.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Phosphorylation controls the three-dimensional structure of plant light harvesting complex II.

The most abundant chlorophyll-binding complex in plants is the intrinsic membrane protein light-harvesting complex II (LHC II). LHC II acts as a light-harvesting antenna and has an important role in the distribution of absorbed energy between the two photosystems of photosynthesis. We used spectroscopic techniques to study a synthetic peptide with identical sequence to the LHC IIb N terminus found in pea, with and without the phosphorylated Thr at the 5th amino acid residue, and to study both forms of the native full-length protein. Our results show that the N terminus of LHC II changes structure upon phosphorylation and that the structural change resembles that of rabbit glycogen phosphorylase, one of the few phosphoproteins where both phosphorylated and non-phosphorylated structures have been solved. Our results indicate that phosphorylation of membrane proteins may regulate their function through structural protein-protein interactions in surface-exposed domains.

Amino Acid Sequence↗