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Biomedical subjects

L Nilsson

Publications and source records attributed to L Nilsson.

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

Couples' willingness to pay for IVF/ET.

BACKGROUND: Many politicians and decision-makers in health care consider assisted reproduction an expensive and exclusive treatment despite the results of in vitro fertilization/embryo transfer (IVF/ET) treatments having improved considerably during the last few years. With the improved results the costs in relation to successful outcome are decreasing. AIM AND METHODS: The aim of this study was to evaluate the cost-benefit of IVF/ET treatments in a group of infertile couples. The benefit was measured as willingness to pay (WTP) for IVF/ET treatment and was related to the cost of IVF/ET: For the calculation of costs, data from one private and one public IVF clinic in Sweden during the period from January 1992 to March 1993 were used. RESULTS AND CONCLUSIONS: The cost analysis showed a direct cost for IVF/ET of 3,170 pounds per started treatment and 9,410 pounds per delivery. Including the indirect cost, the total cost was 3,880 pounds per started IVF/ET treatment and 11,490 pounds per delivery. The survey of the WTP showed that the infertile couples gave high economic priority to infertility treatment. A majority of the couples were willing to pay more for a child than the calculated direct cost.

Attitude to Health↗
PubMed1995

The success rate in a Swedish in-vitro fertilization unit: a cohort study.

OBJECTIVE: To evaluate the cumulative childbirth rate after completion of in vitro fertilization (IVF) treatment including three or, in a few cases, four stimulated cycles. DESIGN: A cohort of 398 couples starting their first IVF treatment between January 1990 and December 1992 were followed until completion of their treatment. RESULTS: Of 826 started cycles, embryo transfer was performed in 793 cycles, giving a mean of 2.0 completed cycles per couple. In addition, cryopreserved embryos were transferred in 228 cycles (0.57 cycles per couple). 204 couples completed their treatment with delivery or with an ongoing pregnancy, 95 couples underwent three stimulated cycles without achieving an ongoing pregnancy and 66 couples cancelled their treatment after one or two cycles because of varying reasons. In seven women no transfer took place. Twenty-six women have not yet completed their planned cycles. Of 398 couples, where the vast majority had completed their IVF treatment, 51% (204) delivered as a result of the treatment. CONCLUSION: IVF treatment combined with freezing of surplus embryos, is a highly effective procedure giving a 'take home baby rate' on a cumulative basis of more than 50% within 1 to 3 cycles.

Adult↗
PubMed1995

Reliability of blood alcohol determinations at clinical chemistry laboratories in Sweden.

Known concentrations of ethanol, methanol, isopropanol and its metabolite acetone were added to plasma or whole blood and aliquots of each specimen were sent to clinical chemistry laboratories in Sweden as a declared collaborative study. All participants used gas-liquid chromatography (GC) for quantitative determination of ethanol and other low molecular weight volatiles. The mean within laboratory precision for analysis of ethanol, expressed as coefficient of variation (CV), was 4.7% (range 0-15%). The corresponding between-laboratory CV spanned from 8.0 to 19.4% for 23 control specimens analysed between 1987 and 1992. The mean concentration of ethanol reported was not significantly different from the target value assigned. Between 0 and 3 laboratories reported deviant results (Z-score > 1.96) for each of the control specimens. One laboratory reported the presence of methanol instead of ethanol and three laboratories saw traces of acetone instead of the actual concentration present. One laboratory failed to report that methanol was present and another failed to report the presence of isopropanol. The between-laboratory CV ranged between 9.4 and 30.3% for analysis of methanol in 8 control specimens. The larger variability between laboratories compared with within laboratories probably reflects the different calibration procedures used, such as the preparation and source of the alcohol standards.

1-Propanol↗
PubMed1995

The effect of graduated elastic compression stockings on femoral blood flow velocity during late pregnancy.

The effect on femoral vein flow velocity of graduated compression was studied in ten women during late pregnancy. The maternal heart rate increased significantly when the position was changed from supine to vertical. This orthostatic increase was significantly reduced when graduated compression exerting 25 mmHg at the ankle level was applied. Closely related to these findings was a significantly decreased femoral vein flow velocity in the vertical position, less pronounced when graduated compression was used. The flow velocity was also significantly higher with compression than without in the standing position. These findings support the use of graduated compression during late pregnancy.

Adult↗
PubMed1995

Upregulation of a non-ETA receptor in human arteries in vitro.

Receptor turnover may be a crucial part in the physiology of endothelin (ET). Incubation of vessel segments could be a possible method to demonstrate this. The aim was to study contractile responses of human omental arteries to different ET agonists at various periods after incubation at 37 degrees C in 5% CO2 and air. The maximum effect (Emax; percentage of contraction to 60 mM K+ buffer solution) and the potency of ET-1 were unaltered (pD2 = 8.82 +/- 0.06). The selective ETB agonist IRL 1620 demonstrated a negligible Emax in nonincubated segments (2.4 +/- 0.9%). After only 1 day of incubation the Emax was 51 +/- 23%, and it reached 114 +/- 53% after 5 days. The pD2 of IRL 1620 was stable throughout the incubation time (7.23 +/- 0.08). ET-3 showed a moderate Emax in nonincubated segments (55 +/- 18%), with a pD2 of 6.68 +/- 0.24. However, subsequent incubation revealed an increase of pD2 to 8.60 +/- 0.20 on the fifth day. The maximum contraction increased to 206 +/- 44%; this is equal to the contraction obtained in paired experiments with ET-1 (215 +/- 18%). These findings indicate modulation of endothelin receptor expression after incubation of vessel segments, and suggest the gradual appearance of a non-ETA receptor.

Aged↗
PubMed1995

Visceral leishmaniasis in Somalia. Circulating antibodies as measured by DAT, immunofluorescence and ELISA.

Sera from patients with visceral leishmaniasis (VL) (n = 26), healthy residents of Mogadishu (n = 157), inhabitants of a village in an endemic area (n = 276) and healthy Swedes (n = 60) were examined using the direct agglutination test (DAT), immunofluorescence (IF) and ELISA for antibodies against Leishmania donovani. The study was carried out in order to provide baseline data for antibody responses in visceral leishmaniasis as existing in Somalia and to explore which one of these methods would be most suitable for diagnosis of clinical cases as well as for epidemiological population studies in Somalia. All patients had high levels of circulating antibodies, however, lower values were recorded in the early stages of the disease. High reactivity in ELISA was seen first after one year. All three tests distinguished well between sera from VL patients and healthy controls. Approximately 10% of the sera from villagers were reactive above the cut-off levels in the three tests. DAT is the simplest to perform and does not require much equipment. ELISA can be made simple and economic if performed in one serum dilution and read visually. IF requires more expensive and specialized equipment and is not suitable for large scale examination of sera. A complete evaluation of the three tests should also include the analysis of sera from various stages and manifestations of the disease.

Adolescent↗
PubMed1994

Structural basis for chromosome X-linked agammaglobulinemia: a tyrosine kinase disease.

X-linked agammaglobulinemia (XLA) is a hereditary defect of B-cell differentiation in man caused by deficiency of Bruton tyrosine kinase (BTK). A three-dimensional model for the BTK kinase domain, based on the core structure of cAMP-dependent protein kinase, was used to interpret the structural basis for disease in eight independent point mutations in patients with XLA. As Arg-525 of BTK has been thought to functionally substitute for a critical lysine residue in protein-serine kinases, the mutation Arg-525-->Gln was studied and found to abrogate the tyrosine kinase activity of BTK. All of the eight mutations (Lys-430-->Glu, Arg-520-->Glu, Arg-525-->Gln, Arg-562-->Pro, Ala-582-->Val, Glu-589-->Gly, Gly-594-->Glu, and Gly-613-->Asp) were located on one face of the BTK kinase domain, indicating structural clustering of functionally important residues.

Adenosine Triphosphate↗
PubMed1994

Structural basis of SH2 domain mutations in X-linked agammaglobulinemia.

The three-dimensional structure of Bruton's agammaglobulinemia tyrosine kinase (Btk) SH2 domain was modeled based on v-Src. Btk SH2 is presumably very related to the other SH2 structures consisting of two beta-sheets surrounded by two alpha-helices, with a well conserved hydrophobic core and phoshotyrosyl peptide binding site. The model was used to predict the recognition sequence of the target protein, which probably is YEXI/L. Mutations in the Btk sequence can cause the human disease X-linked agammaglobulinemia and reasons for the disease in Btk SH2 mutations were inferred from the model.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci.

Btk is a cytoplasmic protein tyrosine kinase (PTK) that has been directly implicated in the pathogenesis of X-linked agammaglobulinaemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. We have isolated phage and cosmid clones that allowed us to deduce the genomic structure of mouse and human Btk loci. The mouse and human genes are contained within genomic regions that span approximately 43.5 kb and 37.5 kb, respectively. Both loci contain 18 coding exons ranging between 55 and 560 bp in size with introns ranging in size from 164 bp to approximately 9 kb. The 5'-untranslated regions are encoded by single exons located approximately 9 kb upstream of the first coding exon. Exon 18 encodes for the last 23 carboxyl-terminal amino acids and the entire 3'-untranslated region. The location of intron/exon boundaries in the catalytic domains of the mouse and human Btk loci differs from that found in other described sub-families of intracellular PTKs, namely that of Src, Fes/Fer, Csk, and Abl/Arg. This observation is consistent with the classification of Btk together with the recently characterized kinases, Tec and Itk, into a separate sub-family of cytoplasmic PTKs. Putative transcription initiation sites in the mouse and human Btk loci have been determined by using the rapid amplification of cDNA ends assay. Similar to many other PTK specific genes, the putative Btk promoters lack obvious TATAA and CAAAT motifs. Putative initiator elements and potential binding sites for Ets (PEA-3), zeste, and PuF transcription factors are located within the 300 bp which are located upstream of the major transcription start site in both species. These sequences can mediate promoter activity when placed upstream of a promotorless chloramphenicol acetyl transferase reporter gene in an orientation-dependent manner. The present analysis will significantly facilitate the mutational analyses of patients with XLA and the further characterization of the function and regulation of the Btk molecule.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

Specific residues at the top of transmembrane segment V and VI of the neurokinin-1 receptor involved in binding of the nonpeptide antagonist CP 96,345 [corrected].

Previously we have found that binding of the nonpeptide substance P antagonist, CP 96,345, to the neurokinin-1 (NK-1) receptor was critically dependent on two short segments adjacent to the top of transmembrane segments (TM) V and VI, called segments A (residues 183-195) and D (residues 271-276), respectively. In the present study we have systematically performed substitutions of nonconserved residues within these two segments with residues from the homologous NK-3 and/or NK-2 receptor. In segment A, deletion of residues Glu193 and Lys194, which are not present in the NK-3 receptor, or substituting them with leucines as in the NK-2 receptor, decreased the affinity of CP 96,345 10- and 22-fold, respectively. Surprisingly, switching the position of Glu193 and Lys194 did not affect the affinity of CP 96,345, suggesting that, rather than interacting directly with CP 96,345, an interaction of these residues with one another is important for CP 96,345 binding. In segment D substitution of Tyr272 with threonine as in the NK-2 receptor and with alanine as in the NK-3 receptor decreased the affinity of CP 96,345 7- and 24-fold, respectively. Mutation of the preceding Pro271 to glycine alone did not affect CP 96,345 binding, but, combined with the mutation of Tyr272 to threonine, the affinity decreased 28-fold. A series of CP 96,345 analogues with modifications of the major chemical moieties exhibited equally reduced affinity as that of CP 96,345 for the Tyr272- and Lys193-Glu194-substituted constructs, except CP 95,555, which lacks one of the phenyl rings in the benzhydryl group and which was almost unaffected by these mutations. In conclusion, our data indicate a direct interaction between CP 96,345 and Tyr272, which are located at the top of TM VI likely in close spatial proximity to the previously identified interaction point, His197, at the top of the adjacent TM V. Furthermore, the data demonstrated a critical involvement in CP 96,345 binding of Lys193 and Glu194 located one alpha-helical turn above His197.

Amino Acid Sequence↗
PubMed1994

Tec homology (TH) adjacent to the PH domain.

The pleckstrin homology (PH) domain is extended in the Btk kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain. The TH domain contains a conserved 27 amino acid stretch designated the Btk motif and a proline-rich region. Sequence similarity was found to a putative Ras GTPase activating protein and a human interferon-gamma binding protein both in the PH domain and the Btk motif region. SLK1/SSP31 protein kinase and a non-catalytic p85 subunit of PI-3 kinase had similarity only with the proline rich region. The identification of a PH domain extension in some signal transduction proteins in different species suggests that this region is involved in protein-protein interactions.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

Deletion within the Src homology domain 3 of Bruton's tyrosine kinase resulting in X-linked agammaglobulinemia (XLA).

The gene responsible for X-linked agammaglobulinemia (XLA) has been recently identified to code for a cytoplasmic tyrosine kinase (Bruton's agammaglobulinemia tyrosine kinase, BTK), required for normal B cell development. BTK, like many other cytoplasmic tyrosine kinases, contains Src homology domains (SH2 and SH3), and catalytic kinase domain. SH3 domains are important for the targeting of signaling molecules to specific subcellular locations. We have identified a family with XLA whose affected members have a point mutation (g-->a) at the 5' splice site of intron 8, resulting in the skipping of coding exon 8 and loss of 21 amino acids forming the COOH-terminal portion of the BTK SH3 domain. The study of three generations within this kinship, using restriction fragment length polymorphism and DNA analysis, allowed identification of the mutant X chromosome responsible for XLA and the carrier status in this family. BTK mRNA was present in normal amounts in Epstein-Barr virus-induced B lymphoblastoid cell lines established from affected family members. Although the SH3 deletion did not alter BTK protein stability and kinase activity of the truncated BTK protein was normal, the affected patients nevertheless have a severe B cell defect characteristic for XLA. The mutant protein was modeled using the normal BTK SH3 domain. The deletion results in loss of two COOH-terminal beta strands containing several residues critical for the formation of the putative SH3 ligand-binding pocket. We predict that, as a result, one or more crucial SH3 binding proteins fail to interact with BTK, interrupting the cytoplasmic signal transduction process required for B cell differentiation.

Adult↗
PubMed1994

Factor for inversion stimulation-dependent growth rate regulation of individual tRNA species in Escherichia coli.

We have studied the involvement of the factor for inversion stimulation (FIS) in the growth rate-dependent expression of the arginine, leucine, and methionine acceptor tRNA species. The concentration of individual tRNA species relative to 16 S rRNA was determined by blot hybridization using RNA preparations from bacteria with the fis gene deleted and from isogenic wild type bacteria. The RNA preparations were obtained from bacteria growing under steady state conditions in different media. The levels of tRNA(1Leu), tRNA(2Arg), tRNA(4Arg), and tRNA(5Arg decreased in the fis bacteria, relative to the wild type. The difference in levels increased with increasing growth rate. Surprisingly, tRNA(3Leu), tRNA(rMet), and tRNA(eMet) showed the opposite response, with an increase of the tRNA/16 S ratio in the fis bacteria. The tRNA(2Leu, tRNA(4Leu), tRNA(5Leu), and tRNA(3 Arg) had unaffected tRNA/16 S ratios in fis cells. We conclude that FIS, directly or indirectly, is involved in growth rate regulation of some tRNA species and that it affects the composition of the cellular tRNA pool.

Base Sequence↗
PubMed1994

Molecular analysis of IgA deficiency. Evidence for impaired switching to IgA.

The most common form of primary immunodeficiency is IgA deficiency (IgAD). However, the molecular basis of this disease remains elusive. Therefore, to address this issue we made a systematic analysis of the molecular events leading to IgA production. B lymphocytes that produce IgA have undergone somatic rearrangement that joins the switch (S) mu to S alpha region with deletion of the intervening sequences. Examination of the resulting S mu/S alpha junctions in unstimulated PBMC from IgAD patients by nested primer PCR revealed a significant decrease in the number of the S mu/S alpha fragments. To obtain the antisense primers to generate the S mu/S alpha fragments, we sequenced the human S alpha 1 and the downstream region extending to the C alpha 1 locus. Similar to previously reported switch sequences, we also found the S alpha 1 to be predominantly composed of pentameric repeats GAGCT and GGGCT. The decrease in the number of S mu/S alpha fragments is consistent with a profound decrease in the C alpha membrane mRNA expression in unstimulated PBMC, as well as in the C alpha mRNA levels and IgA production in PWM-stimulated PBMC. Sequence analysis of the switch junctions from IgA-producing cell lines, control donors, and an IgAD patient showed direct joining in 8 of 9 cases examined. TGF-beta 1, previously shown to be the switch factor for human and mouse IgA, was also examined. No difference in the TGF-beta 1 mRNA levels in unstimulated PBMC between the control subjects and the IgAD patients were detected. Our findings indicate that the failure to switch to IgA-producing B lymphocytes, or an impaired survival of such cells, may be an important molecular mechanism in IgAD.

Animals↗
PubMed1994

Changes in driver behaviour as a function of handsfree mobile phones--a simulator study.

The effects of a mobile telephone task on drivers' reaction time, lane position, speed level, and workload were studied in two driving conditions (an easy or rather straight versus a hard or very curvy route). It was predicted that the mobile telephone task would have a negative effect on drivers' reaction time, lane position, and workload and lead to a reduction of speed. It was also predicted that the effects would be stronger for the hard driving task. The study was conducted in the VTI driving simulator. A total of 40 subjects, experienced drivers aged 23 to 61, were randomly assigned to four experimental conditions (telephone and easy or hard driving task versus control and easy or hard driving task). Contrary to the predictions, the strongest effects were found when the subjects were exposed to the easy driving task. In the condition where drivers had to perform the easy driving task, findings showed that a mobile telephone task had a negative effect on reaction time and led to a reduction of the speed level. In the condition where drivers had to perform the hard driving task, findings showed that a mobile telephone task had an effect only on the drivers' lateral position. Finally, the mobile telephone task led to an increased workload for both the easy and the hard driving task. The results are discussed in terms of which subtask, car driving or telephone task, the subjects gave the highest priority. Some implications for information systems in future cars are discussed.

Adult↗
PubMed1994

Appearance of atopic disease in relation to serum IgE antibodies in children followed up from birth for 4 to 15 years.

BACKGROUND: Few studies have addressed the relationship between sensitization and the development of atopic disease over many years. OBJECTIVE: To study the temporal relationship between the appearance of IgE antibodies in serum and atopic disease, we studied 324 children from three different groups, who were followed up prospectively from birth for 4, 12, and 15 years, respectively. METHODS: Serum samples were obtained at various ages and analyzed for IgE antibodies against egg white, cow's milk, wheat, animal dander, house dust mite, birch and timothy with Phadebas RAST (Kabi Pharmacia Diagnostics AB, Uppsala, Sweden) or Pharmacia CAP system. In addition, a screening test for atopy, the Phadiatop Paediatric test (Kabi Pharmacia Diagnostics AB) was performed. Presence of atopic disease was assessed by means of clinical examination, interviews, and questionnaires. RESULTS: In 135 children IgE antibodies were detected at least once to at least one allergen. Antibodies to egg white appeared in 46 children before or at 2 years of age: in 57% of them IgE antibodies to inhalants developed within the next 2 years, and in 19 of 25 (76%) IgE antibodies to inhalants developed before or at 12 to 15 years. Antibodies to inhalant allergens appeared in 55 children during the first 4 years of life and in 64 before 12 to 15 years. Among the former 48% and among the latter 32% had previously detectable egg white antibodies. Atopic disease appeared before or at age 4 years in 80% of the 40 children with IgE antibodies against egg white up to 9 months of age and in 69% of the 58 children who had a positive Phadiatop Paediatric test result in infancy. CONCLUSIONS: IgE antibodies in children are usually associated with current or later topic disease. Sensitization to foods in infants is usually associated with appearance of IgE antibodies to inhalants later in life.

Adolescent↗
PubMed1994

Stacking-unstacking of the dinucleoside monophosphate guanylyl-3',5'-uridine studied with molecular dynamics.

Molecular dynamics simulations were carried out on two conformations of the dinucleoside monophosphate guanylyl-3',5'-uridine (GpU) in aqueous solution with one sodium counterion. One stacked conformation and one with the C3'-O3'-P-O5' backbone torsion angle twisted 180 degrees to create an unstacked conformation. We observed a relatively stable behavior of the stacked conformation, which remained stacked throughout the simulation, whereas the unstacked conformation showed major changes in the backbone torsion and glycosidic angles. During the simulation the unstacked conformation transformed into a more stacked form and then back again to an unstacked one. The calculated correlation times for rotational diffusion from the molecular dynamics simulations are in agreement with fluorescence anisotropy and nuclear magnetic resonance data. As expected, the correlation times for rotational diffusion of the unstacked conformation were observed to be longer than for the stacked conformation. The 2'OH group may contribute in stabilizing the stacked conformation, where the O2'-H...O4' hydrogen bond occurred in 82.7% of the simulation.

Computer Simulation↗