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Biomedical subjects

B Nilsson

Publications and source records attributed to B Nilsson.

At least 181 records · Page 10Linked to original sources
PubMed1995

Direct and competitive kinetic analysis of the interaction between human IgG1 and a one domain analogue of protein A.

Direct and competitive kinetic analysis of the binding between a one domain analogue of protein A, and mutants thereof, to immobilised hIgG1 was compared using a biosensor system based on surface plasmon resonance detection. Rate constants determined from both assays were almost identical. The experiments demonstrate that competitive kinetic analysis can be used in combination with biosensor technology, and indicate that competitive kinetic analysis may extend the use of the technology to include low molecular weight analytes.

Allergy and Immunology↗
PubMed1995

In vivo and in vitro interactions between idiotypic and antiidiotypic monoclonal antibodies against placental alkaline phosphatase.

A monoclonal antiidiotypic antibody alpha H7, was generated against a monoclonal antibody H7 with specificity towards placental alkaline phosphatase. The in vitro and in vivo effects of alpha H7 were investigated. The antiidiotypic antibody was found to generate stable complexes with the radiolabeled idiotypic antibody, visualized both in vivo and in vitro, as revealed by PAGE and autoradiography. Using biosensor technology (BIAcore, Pharmacia) the interactions were followed in real time and the association rate, dissociation rate, and affinity constants between the reactants were determined (KA H7/PLAP 6.7 x 10(9) M-1, KA H7/alpha H7 3.2 x 10(9) M-1). By in vivo injection of the antiidiotype, a rapid dose dependent clearance of circulating radiolabeled idiotypes was demonstrated and a decrease in total body radioactivity was recorded with a concomitant dramatic increase in non-protein-bound 125I excreted in the urine. It is concluded that idiotypic-antiidiotypic interactions offer advantages in the regulation of antibody levels in vivo.

Aged↗
PubMed1995

Prognostic value of erb-B2 and myc amplification in breast cancer imprints.

BACKGROUND: Amplification of erb-B2 and myc shows prognostic value in patients with operable breast cancer. Amplification is usually detected in tumor samples remaining after pathologic work-up, preventing the examination of small tumors. METHODS: Tumor imprints that contained low numbers of contaminating normal cells were obtained from small tumors. The prognostic value of erb-B2 and myc amplification in imprint breast preparations was examined, using the polymerase chain reaction (PCR) to determine gene copy number. Tumor material was obtained from 162 patients with breast cancer operated 1975-1976. RESULTS: Amplification of erb-B2 existed in 21% and myc in 16% of the patients. Both erb-B2 and myc amplification showed prognostic significance in univariate analysis for survival and relapse free survival. In multivariate analysis, erb-B2 was a significant factor. In small tumors less than 13 mm in greatest dimension, erb-B2 showed prognostic significance for survival but not for relapse free survival. CONCLUSIONS: The use of imprints/PCR allows the detection of gene amplification in breast cancer. The procedure is suitable for the analysis of small tumors and can be used to examine very small tumors, such as those detected mammographically.

Analysis of Variance↗
PubMed1995

Effects of 12 weeks of ramipril treatment on the quality of life in patients with moderate congestive heart failure: results of a placebo-controlled trial. Ramipril Study Group.

The assessment of quality of life (QoL) has become recognized as an important tool for evaluating heart failure therapy. The angiotensin-converting enzyme inhibitor ramipril (mean dose 8 mg) was evaluated in 223 patients with moderate chronic congestive heart failure at 24 centers in 4 Nordic countries following a randomized, double-blind, placebo-controlled, parallel group design. The follow-up period was 12 weeks. QoL was evaluated using a questionnaire with 47 items, including the disease-specific Severe Heart Failure Questionnaire, the Sleep Dysfunction Scale, and the Psychological General Well-Being Index. In both treatment groups the total score increased from baseline to 12 weeks for both the Severe Heart Failure Questionnaire and for the Psychological Well-Being Index, reflecting relief of symptoms and improved well-being. However, no significant differences between the placebo and ramipril groups could be detected. Only a trend toward improvement in sleep on ramipril compared with placebo therapy was observed. In conclusion, in this placebo-controlled trial no significant effects of 12-week ramipril treatment of QoL could be demonstrated in patients with moderate congestive heart failure.

Adult↗
PubMed1995

Impairments in complement receptor- and Fc receptor-mediated functions in vivo in patients with psoriasis.

The function of the fixed macrophage system in 18 psoriasis patients was evaluated by measuring the elimination rate of injected autologous erythrocytes coated with iC3b or IgG. The mean half-life of iC3b-coated erythrocytes was significantly prolonged in patients with psoriasis compared with healthy controls (4.7 +/- 0.8 vs 2.7 +/- 0.2 min, P = 0.01). There was also a decrease in the total number of cells eliminated from the circulation (2.5 +/- 0.2 x 10(8) vs 3.3 +/- 0.2 x 10(8), P = 0.01). There was an even more pronounced increase in the half-life of IgG-coated erythrocytes (85 +/- 18 vs 20 +/- 5 min, P < 0.001), with normal values in only 5 of 15 patients, and 4 of these 5 patients were receiving systemic treatment. The slow elimination was interpreted as being caused by primary or secondary defects in receptor function rather than by blocking of the receptors by immune complexes, since patients with psoriasis show normal levels of circulating immune complexes. Further studies are needed to elucidate the nature of these defects.

Adolescent↗
PubMed1995

Antibody engineering.

Antibody engineering has been an extremely intensive research area for many years. Recent achievements discussed in this review include: (i) significant improvements in the field of selection of antigen-specific antibody fragments on bacteriophages; (ii) new structural work, in particular using NMR; (iii) the cloning of essentially the complete set of human VH genes; (iv) the use of antibodies to catalyze complicated chemical reactions; and (v) novel antibody fusion proteins to potentiate immune therapy. An interesting new development is the replacement of antibodies with more stable protein scaffolds for many future biotechnological applications.

Antibodies↗
PubMed1995

The influence of VDT work on musculoskeletal disorders.

Relationships between visual display terminal (VDT) use and musculoskeletal problems were examined in a group of 353 office workers, using data from medical and workplace investigations as well as questionnaires. There were no general differences between VDT and non-VDT users as to the occurrence of muscle problems. Combinations of specific VDT work situations such as data entry work or work with a VDT for more than 20 h/week and the presence of some other factors were, however, associated with excess risks of certain muscle problems. The extraneous factors involved in the definitions of such risk groups were: use of bifocal or progressive glasses at a VDT; stomach-related stress reactions; limited rest break opportunity; repetitive movements; non-use of lower arm support; and possibly the vertical position of the keyboard; and presence of specular glare.

Cohort Studies↗
PubMed1995

Musculoskeletal disorders among visual display terminal workers: individual, ergonomic, and work organizational factors.

A number of individual, ergonomic, and organizational factors of presumed importance for the occurrence of musculoskeletal disorders were investigated in a group of 260 visual display terminal (VDT) workers. The cross-sectional study utilized medical and workplace investigations as well as questionnaires. The results were subjected to a multivariate analysis in order to find the major factors associated with various upper-body muscular problems. Several such factors were identified for each investigated type of musculoskeletal problem. Some were related to the individual: age, gender, woman with children at home, use of spectacles, smoking, stomach-related stress reactions, and negative affectivity. Organizational variables of importance were opportunities for flexible rest breaks, extreme peer contacts, task flexibility, and overtime. Identified ergonomic variables were static work posture, hand position, use of lower arm support, repeated work movements, and keyboard or VDT vertical position.

Adult↗
PubMed1995

A combinatorial library of an alpha-helical bacterial receptor domain.

The construction and characterization of a combinatorial library of a solvent-exposed surface of an alpha-helical domain derived from a bacterial receptor is described. Using a novel solid-phase approach, the library was assembled in a directed and successive manner utilizing single-stranded oligonucleotides containing multiple random substitutions for the variegated segments of the gene fragment. The simultaneous substitution of 13 residues to all 20 possible amino acids was carried out in a region spanning 81 nucleotides. The randomization was made in codons for amino acids that were modelled to be solvent accessible at a surface made up from two of the three alpha-helices of a monovalent Fc-binding domain of staphylococcal protein A. After cloning of the PCR-amplified library into a phagemid vector adapted for phage display of the mutants, DNA sequencing analysis suggested a random distribution of codons in the mutagenized positions. Four members of the library with multiple substitutions were produced in Escherichia coli as fusions to an albumin-binding affinity tag derived from streptococcal protein G. The fusion proteins were purified by human serum albumin affinity chromatography and subsequently characterized by SDS-electrophoresis, CD spectroscopy and biosensor analysis. The analyses showed that the mutant protein A derivatives could all be secreted as soluble full-length proteins. Furthermore, the CD analysis showed that all mutants, except one with a proline introduced into helix 2, have secondary structures in close agreement with the wild-type domain. These results proved that members of this alpha-helical receptor library with multiple substitutions in the solvent-exposed surface remain stable and soluble in E. coli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesins, Bacterial↗
PubMed1995

Medication with ursodeoxycholic acid enhances the biliary clearance of polyethylene glycol 900, but not mannitol.

Ursodeoxycholic acid (UDCA) is a nontoxic bile acid currently used in the treatment of different cholestatic diseases. This bile acid is also considered to be a 'hypercholeretic bile acid'. The effects of daily administration of UDCA on bile flow and the bile acid secretion rate in man are not fully known. The aim of this study was to explore the effects by UDCA on bile flow and its different functions. The biliary clearances of polyethylene glycol 900 (PEG 900) and mannitol were measured simultaneously in patients with an indwelling T tube after cholecystectomy. One group (n = 6) were given UDCA (10 mg/kg/day) for at least 14 days before the investigation and a control group (n = 8) received no bile acid treatment. The bile secretion was studied in acute experiments where bile was drained for 6 h. The bile plasma ratio for PEG 900 was 31 and that for mannitol was 0.7 which corresponds well with the results obtained in different animal species. The relationship between bile flow and the bile salt secretion rate, as expressed by linear regression analysis, showed no difference between the 2 groups (control y = 0.22 + 0.012x, r = 0.61, p < 0.001; UDCA y = 0.20 + 0.016x, r = 0.88, p < 0.001). The relationship between the biliary clearance of PEG 900 and the bile salt secretion rate, as expressed with linear regression analysis, showed a significantly steeper slope for the UDCA-treated patients (control y = 8.1 + 0.34x, r = 0.41, p < 0.05; UDCA y = 5 + 1.58x, r = 0.78, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Prediction of dental caries development in 1-year-old children.

Dietary habits, oral hygiene, fluoride exposure and occurrence of mutans streptococci were studied in 1-year-old children (n = 786) as well as the socio-economic and immigrant background of their parents. The purpose was to evaluate the predictive ability of variables studied in 1-year-old children that could be used to identify children at risk for early caries development. In a multivariate logistic regression analysis, the variables significantly associated with caries at 3.5 years of age were immigrant background (p < 0.001), mother's education (p < 0.001), consumption of sugar-containing beverages (p < 0.001), mutans streptococci (p < 0.05) and candy (p < 0.05). The probability of caries development was 87% when all the variables associated with caries were present at 1 year of age. The relative risk (odds ratio) of those children to develop manifest caries at 3.5 years of age was estimated to be 32 times higher than in the children where corresponding risk factors were not present. The results indicate that prediction at 1 year of age, built on risk factors associated with dental caries, can provide an indication of possible preventive interventions.

Age Factors↗
PubMed1995

Role of nitric oxide in motility and secretion of the feline hepatobiliary tract.

BACKGROUND: Nitric oxide (NO) mediates inhibition of gastrointestinal smooth-muscle cells via nonadrenergic, non-cholinergic (NANC) nervous pathways. The effect of NO on the absorption and secretion by the mucosa of the gastrointestinal and hepatobiliary tracts is less well known. The aim of this study was to evaluate the effects of a pharmacologic blockade of NO synthase on sphincter of Oddi activity, gallbladder function, and bile secretion and to demonstrate the presence of NO synthase-positive neurons in this region. METHODS: Experiments were conducted on anesthetized cats after blockage of noradrenergic and cholinergic neurotransmission. Flow resistance in the sphincter of Oddi, gallbladder fluid absorption and motility, bile outflow from the liver, and bile salt secretion were registered. RESULTS: Flow resistance exerted by the sphincter of Oddi increased dose-dependently in response to the NO synthase blocker NG-nitro-L-arginine. The increase in flow resistance was reversed stereospecifically by L-arginine, the substrate for NO synthesis. No significant effects on bile secretion, gallbladder fluid transport, or gallbladder motility were observed. NO synthase-positive neurons were identified close to the sphincter of Oddi and in the gallbladder mucosa. CONCLUSIONS: This tonically active inhibitory NANC innervation of the sphincter of Oddi may be important in the physiologic regulation of the bile duct pressure.

Animals↗
PubMed1995

Inflammation reduces mucosal secretion of hydrogen ions and impairs concentrating function and luminal acidification in feline gallbladder.

BACKGROUND: The gallbladder mucosa normally absorbs fluid and secretes H+ ions. The fluid secretion in inflamed gallbladders is induced by prostaglandins and mediated by intramural vasoactive intestinal peptide (VIP)-ergic nerves. METHODS: The influence of inflammation on gallblader contents due to secretion of H+ into the lumen. In animals with inflamed gallbladder this acid secretion was reduced; there was secretion of HCO3- and no evident acidification of the gallbladder contents. Injection of VIP antiserum or indomethacin restored H+ secretion and inhibited HCO3- and fluid secretion by the inflamed gallbladder mucosa. An impaired acidification of the gallbladder contents due to mucosal inflammation may reduce the solubility of calcium salts in gallbladder bile and increase the risk of their precipitation in the lumen. CONCLUSION: Mucosal inflammation reduces H+ secretion and impairs acidification of the gallbladder contents.

Amiloride↗
PubMed1995

Improved long-term preservation of the coronary vasculature with University of Wisconsin solution.

Experiments were designed to investigate coronary vascular function after prolonged cold storage of isolated rat hearts, using University of Wisconsin (UW) solution. Hearts perfused with crystalloid cardioplegic solution (Plegisol) were used as controls. After perfusion with 10 ml at 4 degrees C, hearts were stored for 1 or 10 hours in the respective solutions at 4 degrees C. To evaluate coronary vascular function after perfusion and storage, endothelium-dependent vasodilation was induced with 5-hydroxytryptamine (5-HT) and smooth muscle-dependent dilation with nitroglycerin (GTN). After perfusion only, or perfusion plus 1-hour storage, there was no intergroup difference in response to 5-HT and GTN. After 10-hour storage the vasodilatory response to 5-HT was abolished in the Plegisol group and slight vaso-constriction was observed, whereas in the UW group the vasodilatory effect of 5-HT persisted. The findings suggest that UW solution may be more favorable for prolonged cardiac preservation, as the coronary vascular reactivity was less affected.

Adenosine↗
PubMed1995

Synthesis of an N-methyldehydroalanine-containing fragment of microcystin by combination of solid phase peptide synthesis and beta-elimination in solution.

A new method for the synthesis of dehydroalanine (delta Ala)-containing peptides has been developed by combining solid phase peptide synthesis (tert-butyloxycarbonyl/HF-chemistry) with solution synthesis. A sequence from cyanobacterial hepatotoxin microcystin, Ac-D-gamma-Glu-[N-Me-delta Ala]-D-Ala-Leu amide was chosen as a model peptide. The precursor for the synthesis of the dehydroalanine-containing peptide, Ac-D-gamma-Glu-[N,S-diMeCys]-D-Ala-Leu, was synthesized on a solid phase followed by sulfonium salt formation on the resin. The resulting S,S-dimethylated peptide was cleaved from the resin with liquid HF. The HPLC-purified S,S-dimethylated cysteine-containing precursor peptide was subjected to beta-elimination in solution catalysed by DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) in methanol. The final product, Ac-D-gamma-Glu-[N-Me-delta Ala]-D-Ala-Leu amide, was purified by HPLC, and analysed by mass spectrometry and 1H NMR spectroscopy. The stability of the model peptide under acidic, neutral and basic conditions has been studied.

Alanine↗