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Biomedical subjects

D Nilsson

Publications and source records attributed to D Nilsson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Isolation of Lactococcus lactis nonsense suppressors and construction of a food-grade cloning vector.

Nonsense suppressor strains of Lactococcus lactis were isolated using plasmids containing nonsense mutations or as revertants of a nonsense auxotrophic mutant. The nonsense suppressor gene was cloned from two suppressor strains and the DNA sequence determined. One suppressor is an ochre suppressor with an altered tRNA(gln) and the other an amber suppressor with an altered tRNA(ser). The nonsense suppressors allowed isolation of nonsense mutants of a lytic bacteriophage and suppressible auxotrophic mutants of L. lactis MG1363. A food-grade cloning vector based totally on DNA from Lactococcus and a synthetic polylinker with 11 unique restriction sites was constructed using the ochre suppressor as a selectable marker. Selection, following electroporation of a suppressible purine auxotroph, can be done on purine-free medium. The pepN gene from L. lactis Wg2 was subcloned resulting in a food-grade plasmid giving a four- to fivefold increase in lysine aminopeptidase activity.

Alleles↗
PubMed1994

A conserved sequence in tRNA and rRNA promoters of Lactococcus lactis.

A tRNA operon (trnA) from Lactococcus lactis consisting of seven tRNA genes and a 5S rRNA gene was cloned and sequenced. Promoter-fusion of the trnA promoter to a promoter-less beta-galactosidase gene of Leuconostoc mesenteroides resulted in high levels of beta-galactosidase activity in L. lactis. Searching for sequences with similarity to the sequence of the promoter region revealed a consensus sequence of promoters preceeding rRNA operons and tRNA operons from Lactococcus species including a not previously described conserved sequence (AGTT).

Base Sequence↗
PubMed1994

The influence of net water absorption on the permeability of antipyrine and levodopa in the human jejunum.

Food ingestion can influence the absorption of levodopa in the intestine and thereby contribute to fluctuations of motor functions in Parkinson patients. Obstruction of the active transport of levodopa by amino acids can be one factor. Paracellular drug absorption, a route proposed to be influenced by net transport of water across the intestinal epithelium, might occur for a small and hydrophilic drug such as levodopa. In the present study we studied how luminal L-leucine (60 mmol/L), alone or combined with hypotonicity, might stimulate net water absorption, and levodopa uptake in the human small intestine, since this possibly can contribute to the variable intestinal absorption of levodopa. The Loc-I-Gut perfusion technique was used in 10 healthy volunteers to study the effects of induced net fluid absorption on the small intestinal absorption of levodopa (2.5 mmol/L). An induced net fluid absorption was observed only when L-leucine was combined with a hypoosmolar perfusion solution. However, this did not enhance the intestinal permeability of levodopa. In conclusion, we suggest that the variability in the absorption of levodopa in Parkinson's disease cannot be explained by differences in transmucosal water flux in the human small intestine.

Antipyrine↗
PubMed1994

A Lactococcus lactis gene encodes a membrane protein with putative ATPase activity that is homologous to the essential Escherichia coli ftsH gene product.

A gene, encoding a protein homologous to an essential Escherichia coli protein, FtsH, was identified adjacent to the hpt gene and the trnA operon in the Gram-positive bacterium Lactococcus lactis. The deduced amino acid sequence of the gene product showed full-length similarity to FtsH of E. coli, Yme1p of Saccharomyces cerevisiae and a conserved region found in a new family of putative ATPases. In-frame fusions of L. lactis ftsH and phoA1 in E. coli, and immunodetection of the L. lactis FtsH protein in cell fractions using anti-E. coli FtsH serum showed that L. lactis ftsH was expressed and encodes a membrane protein. When contained on a high copy number plasmid, the L. lactis ftsH gene complemented the lethality of a delta ftsH3::kan mutation in E. coli at 37 degrees C and below, indicating that the L. lactis ftsH gene can functionally replace the E. coli ftsH gene to some extent. The resulting E. coli strain showed temperature sensitivity and salt sensitivity. A L. lactis mutant with an insertion into ftsH was salt-, heat- and cold-sensitive. These results suggest that FtsH is somehow involved in stress responses. Southern hybridization analysis indicated that genes homologous to ftsH of L. lactis were also present in Bacillus subtilis, and several Lactobacillus and Leuconostoc species, suggesting high conservation of ftsH in bacterial species.

ATP-Dependent Proteases↗
PubMed1993

Intraduodenal infusion of a water-based levodopa dispersion for optimisation of the therapeutic effect in severe Parkinson's disease.

Motor performance of five patients with advanced Parkinson's disease was investigated during their optimum oral therapy (conventional tablets and/or depot capsules) and during a continuous duodenal infusion of levodopa. Due to the low water solubility of the drug, conventional tablets of levodopa+carbidopa (Sinemet) were milled and dispersed in a 1.8% aqueous methylcellulose solution. The dispersion was delivered nasoduodenally by a portable pump. The effect of levodopa in the two dosing regimens was estimated optico-electronically every 15 min and was also evaluated from videorecordings every 30 min and plasma levels of levodopa was regularly measured. Each dosage regimen the was studied twice, at a 2-4 day interval. Duodenal infusion improved motor function in all five patients and the fluctuations were reduced when compared to the oral therapy. Variation in plasma levodopa concentrations was 3-10 fold during oral therapy, while during the infusion a stable concentration was obtained. The therapeutic concentration varied from 0.3-3 ml-1 between patients. The relative bioavailability of levodopa in the solid preparation compared to the dispersion was in all patients 100%. Our results encourage further development of a duodenal infusion system with a levodopa dispersion for clinical use in parkinsonian patients who show severe fluctuation.

Administration, Oral↗
PubMed1993

The effect of L-leucine on the absorption of levodopa, studied by regional jejunal perfusion in man.

1. A new method for perfusing a 10 cm segment of jejunum in humans has been used in seven subjects to study the effect of the amino acid L-leucine (40 mM) on the intestinal absorption of levodopa (2.5 mM). The tube contains six channels and has two inflatable balloons, which enable a perfusion of a closed and defined segment of the proximal small intestine. 2. L-leucine decreased the intestinal absorption of levodopa from 40 +/- 19 to 21 +/- 15% but was without effect on the absorption of antipyrine, benserazide and D-glucose. 3. We confirm that levodopa is absorbed by the active transport system normally responsible for the absorption of large neutral amino acids (LNAA) in humans. Oral absorption by passive diffusion, probably by the paracellular route, might also occur for levodopa in the proximal part of the small intestine.

Adult↗
PubMed1993

Health service consumption and parent reported episodes of illness in children 0-3 years.

OBJECTIVE: To describe health service consumption and to find out whether a series of possible explanatory variables can help us to predict the number of contacts among children. DESIGN: A prospective study following a cohort of children during the first four years of life. SETTING: A municipality in southern Norway. PARTICIPANTS: 183 children born in the community from October 1979 to and including December 1980. MAIN OUTCOME MEASURE: Direct and indirect encounters with general practitioners (GPs) from the bills to the national insurance office, outpatient encounters and hospital admissions from the hospital files, and episodes of illness as reported in postal questionnaires to the parents. RESULTS: Each child had on average 10.6 GP contacts (2.6 per year), and the frequency of contacts decreased as they grew. Telephone contacts were almost as frequent as consultations at the doctor's surgery, and the doctors made more home visits to the youngest children. Of the contacts, 4/5 took place in the day time, but most of the home visits took place during the evening/night/weekend. Each child had 1.9 hospital contacts in 4 years, i.e. 0.3 admissions and 1.6 outpatient department contacts. The parents reported an average of 11.5 episodes of illness during the period, more than twice as many in the first year as in the last year. Information about sex, duration of breast feeding, smoking in the family, family history of allergy, parents' education, whether in kindergarten, and presence of psychosocial problems cannot help in predicting health care consumption. CONCLUSION: The low number of contacts with GPs can partly be explained by the fact that the children also have contact with a well-baby clinic. In our study, a series of possible explanatory factors did not help us to predict the amount of health care consumption during the first four years of life.

Child Health Services↗
PubMed1992

Isolation of purine auxotrophic mutants of Lactococcus lactis and characterization of the gene hpt encoding hypoxanthine guanine phosphoribosyltransferase.

Five purine auxotrophic mutants of Lactococcus lactis were isolated. L. lactis was capable of converting adenine, guanine and hypoxanthine to AMP, GMP and IMP, respectively, indicating the existence of adenine phosphoribosyltransferase (APRT) and hypoxanthine guanine phosphoribosyltransferase (HGPRT) activities. A 1.3 kb DNA fragment from L. lactis was cloned by complementation of the hpt mutation in Escherichia coli. Introduction of this fragment into L. lactis resulted in an increase in HGPRT activity. In vitro transcription and translation analysis showed that the fragment coded for a polypeptide with M(r) of 22,000. The nucleotide sequence of this hpt gene was determined.

Adenine Phosphoribosyltransferase↗
PubMed1990

Functional and pharmacokinetic studies of tetrahydroaminoacridine in patients with amyotrophic lateral sclerosis.

Assuming the presence of clinically significant cholinergic hypofunction in amyotrophic lateral scleroses (ALS), seven patients with ALS were treated with 100-200 mg tetrahydroaminoacridine (THA) together with 11 g lecithin daily for up to 7 weeks. In a separate experiment pharmacokinetics and effects on muscle strength and neurophysiological parameters were studied following the injection of 30 mg THA intravenously. Following the injection of THA an increase in muscle strength was observed in two patients. There were no consistent pharmacokinetic differences that could explain the effect on intravenous THA on muscle strength in these two patients. The plasma clearance of THA was high and the oral bioavailability low with large interindividual differences (6-36%). No beneficial effect was seen during oral medication and side-effects were common. There were no conclusive changes observed regarding neurophysiological parameters after drug administration. THA has probably no place in the treatment of ALS.

Administration, Oral↗
PubMed1989

Primary structure of the tms and prs genes of Bacillus subtilis.

The nucleotide sequence was determined of a 3211 nucleotide pair EcoRI-PvuII DNA fragment containing the tms and prs genes as well as a part of the ctc gene of Bacillus subtilis. The prs gene encodes phosphoribosylpyrophosphate (PRPP) synthetase, whereas the functioning of the tms and ctc gene products remains to be established. The prs gene contains an open reading frame of 317 codons resulting in a subunit Mr of 34828. An open reading frame comprising the tms gene contained 456 codons resulting in a putative translation product with an Mr of 49,554. Comparison of the deduced B. subtilis PRPP synthetase amino acid sequence with PRPP synthetases from Escherichia coli and rat liver showed extensive similarity. The deduced Tms amino acid sequence was found to be 43% similar to the deduced amino acid sequence of ecourfl, a gene of E. coli with unknown function.

Amino Acid Sequence↗
PubMed1988

No difference in general well-being during antihypertensive treatment with atenolol or metoprolol CR.

Atenolol and metoprolol are the two most widely used beta 1-adrenoceptor antagonists in the treatment of essential hypertension. Differences in their physico-chemical properties have been the basis of a number of clinical studies whose primary or secondary objective has been to compare subjective well-being during treatment with these beta-selective blockers. The results are, however, contradictory, mainly due to factors such as open study design, different dose regimens and dissimilar study populations. The aim of the present study was to evaluate and compare subjective well-being during treatment with atenolol (50 mg o.d.) and metoprolol CR (100 mg o.d.) in a randomized double-blind, cross-over study (2 x 6 weeks) in hypertensives not previously treated with either of the drugs studied. Two self-administered questionnaires (MSE-profile and Jern quality of life questionnaire) were filled in both before randomization and before follow up visits at 1, 3 and 6 weeks in each treatment period. Furthermore, subjective symptoms, blood pressure and heart rate were monitored. At the end of the study, patients were requested to state what treatment they preferred. Atenolol and metoprolol CR were found to be equally effective in reducing blood pressure (from 159/98 to 144/87 and 144/88 mm Hg, respectively, n = 74). The MSE-profile and the Jern quality of life questionnaire could not detect any differences between the two treatments as regards general well-being. Other subjective symptoms (e.g. diarrhoea, bradycardia, cold hands and feet) were uncommon and equally distributed among atenolol and metoprolol patients. 31 of the patients preferred metoprolol CR, 23 atenolol, while 20 had no preference.(ABSTRACT TRUNCATED AT 250 WORDS)

Atenolol↗
PubMed1988

Food intake and patterns of feeding of Norwegian infants.

Norway has formed a policy on infant feeding, expressed as dietary allowances and guidelines concerning food intake. In a longitudinal and prospective study of health and development during infancy, the feeding patterns of 217 Norwegian infants were followed in order to evaluate the policy. The findings indicated that prevailing guidelines were largely followed by the parents. Forty-five per cent still got breastmilk at 6 months. Solid foods were usually introduced around 4-5 months, iron-enriched porridge being commonly used. At 10 months 91 per cent were given bread. The nutrient intakes at 10 months were mainly in accordance with the recommendations. The quality of the diet seemed to diminish somewhat when sandwiches replaced porridge. More emphasis should be put upon toddlers' diet in counselling the parents.

Age Factors↗
PubMed1987

Phosphoribosylpyrophosphate synthetase of Bacillus subtilis. Cloning, characterization and chromosomal mapping of the prs gene.

The gene (prs) encoding phosphoribosylpyrophosphate (PRPP) synthetase has been cloned from a library of Bacillus subtilis DNA by complementation of an Escherichia coli prs mutation. Flanking DNA sequences were pruned away by restriction endonuclease and exonuclease BAL 31 digestions, resulting in a DNA fragment of approx. 1.8 kb complementing the E. coli prs mutation. Minicell experiments revealed that this DNA fragment coded for a polypeptide, shown to be the PRPP synthetase subunit, with an Mr of approx. 40,000. B. subtilis strains harbouring the prs gene in a multicopy plasmid contained up to nine-fold increased PRPP synthetase activity. The prs gene was cloned in an integration vector and the resulting hybrid plasmid inserted into the B. subtilis chromosome by homologous recombination. The integration site was mapped by transduction and the gene order established as purA-guaA-prs-cysA.

Bacillus subtilis↗