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Biomedical subjects

S Pedersen

Publications and source records attributed to S Pedersen.

At least 127 records · Page 7Linked to original sources
PubMed1994

Effect of 4.5S RNA depletion on Escherichia coli protein synthesis and secretion.

We examined the synthesis of individual proteins following depletion of 4.5S RNA by using a strain deficient in the induction of heat shock proteins. We found that initially the synthesis of all proteins was equally affected, and the peptide elongation rate was reduced by approximately 10%. For up to 1 generation time after the onset of inhibition of total protein synthesis, the processing of secreted proteins was unaffected. After further depletion of 4.5S RNA, accumulation of precursors of secreted proteins was observed under some growth conditions.

Bacterial Proteins↗
PubMed1994

Influence of spacer device on drug delivery to young children with asthma.

The budesonide dose delivered to the patient from three different spacer devices (Nebuhaler = 750 ml, Aerochamber = 140 ml, and Babyspacer = 260 ml) was assessed by measuring the budesonide dose deposited on a filter inserted between the spacer outlet and the mouth of the patient. Twenty children aged 10-25 months were given a single dose of 200 micrograms budesonide from each spacer device in a randomised crossover study. All spacers had a facemask attached and a one way valve system. The children breathed through the inhalation system for 30 seconds. Furthermore, the minute ventilation of the children through a tightly fitting facemask was measured. The filter dose of budesonide was significantly lower after Aerochamber treatment (39.4 micrograms, range 19-67 micrograms) than after Nebuhaler (53.5 micrograms, range 34-88 micrograms) and Babyspacer (55.5 micrograms, range 39-76 micrograms) treatment. The minute ventilation of the children varied from 1.4 l/min to 7.0 l/min (mean 5.0 l/min). This was sufficient to empty all spacers within the 30 seconds of inhalation. It is concluded that spacer volume does not seem to be so important for children aged 10-25 months as long as spacers with a volume lower than 750 ml are used.

Administration, Topical↗
PubMed1994

The insulin-like growth factor axis and collagen turnover during prednisolone treatment.

Serum concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), the carboxyterminal propeptide of type I collagen (PICP), the carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied in 10 prepubertal children with asthma (mean age 9.0 years). The children were treated with 2.5 and 5.0 mg/day prednisolone in a randomised double blind crossover trial with run in, treatment, and washout periods of two weeks. No statistically significant effects on serum concentrations of IGF-I and IGFBP-3 were found. Dose related reductions of PICP, ICTP, and PIIINP were observed: the mean (SEM) reduction in PICP was 33.4 (26.3) and 68.4 (20.6) micrograms/l, in ICTP 2.5 (0.5) and 2.9 (0.6) micrograms/l, and in PIIINP 2.1 (0.7) and 3.1 (1.8) micrograms/l during the 2.5 and 5.0 mg prednisolone periods respectively. Short term treatment with low daily doses of prednisolone is associated with suppression of serum markers of type I and III collagen turnover in children with asthma. Intermediate and long term effects remain to be studied.

Asthma↗
PubMed1994

Pseudodicentric chromosome 18 diagnosed by chromosome painting and primed in situ labelling (PRINS).

We report on a newborn white male infant with marked dysmorphic features and various congenital malformations. The initial clinical evaluation showed Crouzon-like features as well as some features of trisomy 18 syndrome and trisomy 13 syndrome. The results from conventional cytogenetic analysis showed a structurally abnormal chromosome replacing one normal chromosome 18, but only by applying molecular cytogenetic methods could the architecture of this abnormal chromosome be characterised clearly. The primed in situ labelling (PRINS) technique, using a newly synthesised alpha 18 oligonucleotide, showed the dicentric pattern and direct chromosome painting established the origin to be from chromosome 18. The combination of conventional cytogenetics and molecular cytogenetics showed the karyotype in the proband to be 45,XY,-14,-18,-21,+t(14;21),+psu dic(18) (qter-->cen-->p11.3: :p11.3-->psu cen-->qter). This was supported by molecular analysis using chromosome 18 specific DNA markers, which showed the paternal origin of the abnormal chromosome.

Abnormalities, Multiple↗
PubMed1994

Value of chromosome painting in determining the chromosomal outcome in offspring of a 12;16 translocation carrier.

We currently use direct and reverse chromosome painting in prenatal diagnosis. In a family with a subtle 12;16 translocation, adjacent 1 segregation was diagnosed in the first child, a boy, in whom symptoms compatible with partial trisomy 16p and partial monosomy 12q were seen. In the next pregnancy, a chorionic villus biopsy was tested using chromosome painting. Only by supplementing conventional cytogenetic methods with molecular cytogenetic techniques could the true karyotype be unequivocally determined. Reverse painting, using DOP-PCR amplified, flow sorted paternal derivative chromosomes as a DNA library to paint the chorionic villus cells, was especially informative.

Abnormalities, Multiple↗
PubMed1994

Use of budesonide Turbuhaler in young children suspected of asthma.

The question addressed in this study was the ability of young children to use a dry-powder inhaler, Turbuhaler. One hundred and sixty five children suspected of asthma, equally distributed in one year age-groups from 6 months to 8 yrs, inhaled from a Pulmicort Turbuhaler, 200 micrograms budesonide-dose-1, through a filter. The amount of drug trapped by the filter was used as a measure of drug released to the patient. None of the children had prior experience in the use of a Turbuhaler, but they were instructed carefully, together with their parents, in the clinic. The median dose released revealed an age-dependent increase, with a considerable scatter. Accordingly, the dose delivered could not be predicted in these young children. The limitation to effective use in young children appeared to be lack of sufficient co-operation, rather than physical limitations, as even some very young children appeared to obtain a sufficient activation of the device. It is likely that repeated training at home may improve these findings. In conclusion, our results indicate that dry-powder inhalers are not reliable in all circumstances for treatment of young children, and that careful and repeated tuition is required if such devices are to be used.

Asthma↗
PubMed1993

Synthesis of proteins in Escherichia coli is limited by the concentration of free ribosomes. Expression from reporter genes does not always reflect functional mRNA levels.

Induction of beta-galactosidase from high copy-number plasmids was found to reduce the synthesis of other cellular proteins in Escherichia coli. The reduction depends on the protein in question and on the induction level of the beta-galactosidase. It could be observed transiently within one minute after induction and in some cases also during steady-state induction. Our interpretation is that the concentration of the free ribosomal subunits decreases after induction, leading to an increased competition among the individual ribosome binding sites for ribosomes. The immediate reduction in the synthesis individual proteins after induction of beta-galactosidase was used as an assay to measure in vivo the efficiency of a ribosome binding site. These efficiencies were compared to the calculated affinities between the ribosome binding site of specific mRNA species and the 3' end of 16 S RNA. For several mRNAs with similar Shine-Dalgarno sequences, the sensitivity to competition differed twofold. Our results show, that both transiently during induction of lacZ and also at very high steady-state expression levels, the expression from reporter genes, including the lacZ gene itself, does not reflect the levels of the mRNAs in a simple way.

Bacterial Proteins↗
PubMed1993

Bone turnover in asthmatic children treated with oral prednisolone or inhaled budesonide.

Biochemical markers of bone turnover were studied in prepubertal school children with asthma in two randomized double-blind crossover trials with run-in, treatment, and wash-out periods of 2 weeks. One group (n = 11) was treated with 2.5 and 5.0 mg prednisolone, the other (n = 14) with 200 and 800 micrograms inhaled budesonide per day. Serum osteocalcin, serum total alkaline phosphatase, fasting urinary excretion of hydroxyproline and calcium, serum 25-hydroxyvitamin D, and 1,25 dihydroxyvitamin D were assessed. A dose-related reduction of serum osteocalcin (Page's test for trend: P = 0.04; z = -2.3) and of the fasting urinary hydroxyproline:creatinine ratio (Page's test for trend: P = 0.05; z = -2.0) was found in the children who were treated with prednisolone. Inhaled budesonide was not associated with statistically significant effects on any of the biochemical markers. Short-term treatment with low daily doses of prednisolone may cause a suppression of bone turnover in children with asthma. To reduce the risk of adverse effects on bone turnover, doses of inhaled budesonide up to 800 micrograms daily may be preferable to low doses of prednisolone. Bone turnover remains to be evaluated during long-term treatment.

25-Hydroxyvitamin D 2↗
PubMed1993

Isolation and characterization of mutants with impaired regulation of rpsA, the gene encoding ribosomal protein S1 of Escherichia coli.

In order to select mutants that would help to characterize the post-transcriptional regulation of rpsA, we constructed a strain in which the growth rate on lactose minimal medium is determined by the amount of an rpsA-lacZ' alpha-fragment fusion protein produced, even when this is encoded by a high-copy-number plasmid. In the parental strain, synthesis of the fusion protein is repressed by a wild-type rpsA gene, present on a compatible plasmid. Twenty-eight spontaneous and independent mutants, all of them mapping in the rpsA leader region, were isolated as strains that showed higher growth rates, on lactose medium, due to increased synthesis of the rpsA-lacZ' fusion protein. Among these mutants only three sequence changes were found, mapping 9, 10 and 27 bases upstream of the rpsA start codon. At both the -9 and -10 positions an A to G transition and at -27 a C to G transversion all resulted in a sequence with better complementarity to the 3' end of 16S rRNA. We also isolated two mutations mapping in the plasmid-encoded rpsA structural gene: an ochre nonsense mutation in codon 15 of the rpsA gene and a frameshift mutation, deleting the T residue at position +1186. To facilitate the in vitro assay of alpha-fragment activity we also constructed a strain that overproduces the alpha-acceptor fragment four-fold relative to a strain that is diploid for this lacZ delta M15 allele.

Bacterial Proteins↗
PubMed1993

The rates of macromolecular chain elongation modulate the initiation frequencies for transcription and translation in Escherichia coli.

Here we show that most macromolecular biosynthesis reactions in growing bacteria are sub-saturated with substrate. The experiments should in part test predictions from a previously proposed model (Jensen & Pedersen 1990) which proposed a central role for the rates of the RNA and peptide chain elongation reactions in determining the concentration of initiation competent RNA polymerases and ribosomes and thereby the initiation frequencies for these reactions. We have shown that synthesis of ribosomal RNA and the concentration of ppGpp did not exhibit the normal inverse correlation under balanced growth conditions in batch cultures when the RNA chain elongation rate was limited by substrate supply. The RNA chain elongation rate for the polymerase transcribing lacZ mRNA was directly measured and found to be reduced by two-fold under conditions of high ppGpp levels. In the case of translation, we have shown that the peptide elongation rate varied at different types of codons and even among codons read by the same tRNA species. The faster translated codons probably have the highest cognate tRNA concentration and the highest affinity to the tRNA. Thus, the ribosome may operate close to saturation at some codons and be unsaturated at synonymous codons. Therefore, not only translation of the codons for the seven amino acids, whose biosynthesis is regulated by attenuation, but also a substantial fraction of the other translation reactions may be unsaturated. Recently, we have obtained results which indicate that also many ribosome binding sites are unsaturated with their substrate, i.e. with ribosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗
PubMed1993

Improved survival in biliary atresia patients in the present era of liver transplantation.

Therapy for patients with biliary atresia (BA) has become controversial, with orthotopic liver transplantation (OLTx) suggested in place of portoenterostomy. This is based on the unpredictable success of portoenterostomy, and the increased difficulty of the OLTx procedure following prior extensive liver surgery. The survival rate reported here for infants transplanted after unsuccessful portoenterostomy does not support this approach. OLTx was undertaken in 37 patients when end-stage liver failure followed primary portoenterostomy. Recipient age ranged from 6 months to 14 years (median, 13 months), and weight ranged from 5 to 45 kg (median, 8 kg) at the time of OLTx. Reduced-size allografts were used as the primary allograft in 25 patients (23 left lobe), and 12 received whole-organ allografts. Retransplantation was required in 5 patients, each received a reduced-size allograft. There was no increased incidence of vascular complications, primary nonfunction, irreversible rejection, intestinal perforation, biliary complications, sepsis, or lymphoma comparing the BA patients with all other non-BA patients who had undergone OLTx (all P = .16). There was no statistically significant difference in mean operative blood loss between BA patients (EBL = 1.99 BV) and non-BA patients (1.50 BV) (P = .14). Actuarial survival for the series of BA patients was 89% at 1 year, and 80% at 2 years. Following the introduction of reduced-size allografts, donor organs were selected for use with a priority on donor stability. The actuarial survival for BA patients during this time has improved to 96% at 1 year, and 91% at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1993

Molecular cytogenetics: applications in clinical genetics.

To illustrate the advantage of fluorescence in situ hybridization (FISH) in clinical genetics, we have chosen six clinical cases from our routine laboratory where we have used molecular cytogenic techniques to optimise the cytogenetic analysis. Using centromere-specific DNA probes and whole chromosome DNA libraries either obtained from somatic cell hybrids or generated from flow-sorted chromosomes, we have been able to identify small marker chromosomes, chromosomal duplications and inversions, to determine the ploidy in interphase nuclei, and to characterize subtle chromosomal translocations. We conclude that molecular cytogenetics is a valuable technique that should be used as a supplement to conventional cytogenetics to reduce the number of unresolved karyotypes in clinical genetics.

Adolescent↗
PubMed1993

Genetic analysis of repeated, biparental, diploid, hydatidiform moles.

A woman presented with five consecutive pregnancies displaying molar morphology. In the fifth pregnancy, a non-malformed, liveborn infant was delivered. Genetic analyses (RFLP analysis, cytogenetics, flow cytometry) were performed in pregnancies II-V. It was demonstrated that these pregnancies originated in separate conceptions, all conceptuses were diploid, and all had maternally as well as paternally derived genetic markers. By cytogenetic analysis, aberrant heteromorphisms were noted; no other abnormalities were observed in chromosome structure or in DNA sequence. Many different causes for the abnormal development can be envisaged, environmental as well as genetic. To conform to current ideas of molar pathogenesis, it is suggested that the present conceptuses might have arisen from imbalances in imprinted genomic regions. This could be a consequence of uniparental disomy in critical regions generated by somatic crossing over. Alternatively, it could be caused by a malfunction in the generation or maintenance of imprinting.

Chromosome Aberrations↗
PubMed1993

Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1.

We have mapped the autosomal sex reversal locus, SRA1, associated with campomelic dysplasia (CMPD1) to 17q24.3-q25.1 by three independent apparently balanced de novo reciprocal translocations. Chromosome painting indicates that the translocated segment of 17q involves about 15% of chromosome 17 in all three translocations, corresponding to a breakpoint at the interphase between 17q24-q25. All three 17q breakpoints were localized distal to the growth hormone locus (GH), and proximal to thymidine kinase (TK1). Due to the distal location of the breakpoints, previously mentioned candidate genes, HOX2 and COL1A1, can be excluded as being involved in CMPD1/SRA1. The mouse mutant tail-short (Ts) which maps to the homologous syntenic region on mouse chromosome 11, displays some of the features of CMPD1.

Abnormalities, Multiple↗
PubMed1993

The influence of orally deposited budesonide on the systemic availability of budesonide after inhalation from a Turbuhaler.

1. The aim of this pharmacokinetic study was to evaluate to what extent oropharyngeal deposition of drug contributes to the systemic availability of budesonide inhaled from a dry powder inhaler (Turbuhaler). 2. The design was a randomized cross-over study in eight children aged 7-13 years. The plasma concentrations of the two epimers of budesonide (22R and 22S) after inhalation of 1 mg budesonide from a Turbuhaler were compared with the plasma concentrations obtained when the absorption of the drug deposited in the oropharynx was blocked by drinking and rinsing the mouth with charcoal before and after the inhalation. 3. The plasma concentrations of budesonide were significantly reduced by the charcoal treatment (P < 0.01) and the area under the time vs plasma concentration curve 0-4 h was significantly reduced from 9.5 to 8.0 mmol l-1 h for 22S (P < 0.01) and from 7.6 to 5.7 mmol l-1 h for 22R (P < 0.01). 4. The plasma concentrations and the AUCs after both Turbuhaler administrations were markedly higher than those obtained in earlier studies using other inhalers suggesting a higher intrapulmonary deposition of drug after Turbuhaler treatment. 5. It is concluded that oropharyngeal deposition of drug accounts for about 20% of the total systemic availability of budesonide inhaled from Turbuhaler. Thus, the main contribution to the system comes from budesonide absorbed in the airways.

Administration, Inhalation↗
PubMed1993

Ring chromosome 20 with loss of telomeric sequences detected by multicolour PRINS.

A ring chromosome 20 in a male infant with epileptic seizures, mental and somatic growth retardation, and behavioural disturbances is described. Conventional cytogenetics revealed the karyotype to be 46,XY,r(20)(pter-->qter) and no signs of mosaicism were found. Fluorescence in situ hybridisation using the clone p20Z1 identified the ring to be derived from chromosome 20. By counting 111 metaphases, only 7% were found to be missing the ring. The absence of telomeric sequences in the ring chromosome was demonstrated by multicolour PRINS: a three-step PRimed IN Situ labelling technique, using unlabelled primers. A terminal deletion of both arms thus seems to be the cause of the ring formation in the proband. Bivariate flow-analysis of chromosomes verified a deletion of the ring chromosome. The clinical and cytogenetic findings are compared with previous cases. A specific ring 20 syndrome seems justified.

Abnormalities, Multiple↗