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- Janson, Håkan, et al.
(author)
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Protein D, the glycerophosphodiester phosphodiesterase from Haemophilus influenzae with affinity for human immunoglobulin D, influences virulence in a rat otitis model
- 1994
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In: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 62:11, s. 4848-4854
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Journal article (peer-reviewed)abstract
- A mutant lacking the ability to express the surface-exposed lipoprotein protein D was constructed by linker insertion and deletion mutagenesis of a cloned DNA insert containing the protein D structural gene from a nontypeable Haemophilus influenzae strain (NTHi). An isogenic NTHi mutant was isolated after transformation of genetically competent bacteria. The transformant was unreactive to a protein D-specific monoclonal antibody in a colony immunoassay. In addition, the mutant lacked the ability to synthesize detectable levels of protein D by protein staining, immunoblot methods, glycerophosphodiester phosphodiesterase activity, and binding studies of radiolabelled immunoglobulin D. The isogenic protein D-deficient mutant was compared with its parental strain for its ability to induce experimental otitis media in rats challenged with bacteria. An approximately 100-times-higher concentration of the mutant compared with that of the wild-type strain was required in order to cause otitis among all rats challenged with that given dose. The protein D mutant exhibited a generation time that was equal to that of the wild-type strain in complex broth medium. No difference in lipopolysaccharide expression was found between the mutant and the parental strain. These results suggest that protein D may influence the pathogenesis of NTHi in the upper respiratory tract.
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- Johanson, Urban, et al.
(author)
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Comparison of the complete sequence of the str operon in Salmonella typhimurium and Escherichia coli
- 1992
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In: Gene. - 0378-1119 .- 1879-0038. ; 120:1, s. 93-98
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Journal article (peer-reviewed)abstract
- The nucleotide (nt) sequences of the str operon in Escherichia coli K-12 and Salmonella typhimurium LT2 were completed and compared at the nt and amino acid (aa) level. The order of conservation at the nt and aa level is rpsL greater than tufA greater than rpsG greater than f usA. A striking difference is that the rpsG-encoded ribosomal protein, S7, in E. coli K-12 is 23 aa longer than in S. typhimurium. The very low (0.18) codon adaptation index of this part of the E. coli K-12-encoding gene and the unusual stop codon (UGA) suggest that this is a relatively recent extension. A trend towards a higher G+C content in fusA (gene encoding elongation factor (EF)-G) and tufA (gene encoding EF-Tu) in S. typhimurium is noted. In fusA, nt substitutions at all three positions in a codon occur at a much higher frequency than expected from the number of nt substitutions in the gene, assuming they are random and independent events. An analysis of substitutions in this and other genes suggests that the triple substitutions in fusA, and some other genes, are the result of the sequential accumulation of individual mutations, probably driven by selection pressure for particular codons or aa.
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| 5. |
- Johanson, U, et al.
(author)
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Fusidic acid-resistant mutants define three regions in elongation factor G of Salmonella typhimurium
- 1994
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In: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 143:1, s. 9-55
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Journal article (peer-reviewed)abstract
- We have sequenced fusA, the gene coding for elongation factor G (EF-G), in 18 different mutants of Salmonella typhimurium selected as fusidic acid resistant (FuR). In addition, we have sequenced two previously described FuR mutants from Escherichia coli. In all cases, the resistance is due to a mutation in one of three separate regions in fusA. The three clusters of mutant sites superimpose on regions that are well conserved, suggesting that they are of a more general functional importance. To further classify the mutants, we have measured the minimal inhibitory concentration (MIC) for Fu and for two other antibiotics which interfere with translocation on the ribosome, kanamycin (Km) and spectinomycin (Sp). The levels of resistance to Fu for each of the mutants are significantly higher than in the wild type (wt), and vary by about one order of magnitude between the highest and the lowest. Most of the mutants are also more resistant to Km than the wt, although the level of resistance is low and the variation small. In contrast, about half of the mutants are more sensitive to Sp than the wt, with only one being more resistant. Only three of the twenty mutants behave like the wt with respect to the non-selected phenotypes, KmR and SpR.
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- Nikkhah, G, et al.
(author)
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Platelet-derived growth factor promotes survival of rat and human mesencephalic dopaminergic neurons in culture
- 1993
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In: Experimental Brain Research. - 0014-4819 .- 1432-1106. ; 92:3, s. 516-523
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Journal article (peer-reviewed)abstract
- The effect of two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, was tested on dissociated cell cultures of ventral mesencephalon from rat and human embryos. PDGF-BB but not PDGF-AA reduced the progressive loss of tyrosine hydroxylase- (TH)-positive neurons in rat and human cell cultures. The mean number of TH-positive cells in the PDGF-BB-treated rat culture was 64% and 106% higher than in the control cultures after 7 and 10 days in vitro, respectively. Corresponding figures for human TH-positive neurons were 90% and 145%. The influence of PDGF-BB was specific for TH-positive neurons and not a general trophic effect, since no change of either total cell number or metabolic activity was found. In PDGF-BB-treated cultures of human but not rat tissue the TH-positive neurons had longer neurites than observed in control or PDGF-AA-treated cultures. These data indicate that PDGF-BB may act as a trophic factor for mesencephalic dopaminergic neurons and suggest that administration of PDGF-BB could ameliorate degeneration and possibly promote axonal sprouting of these neurons in vivo.
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- Rydhstrom, Håkan, et al.
(author)
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No relation between maternal weight gain and stillbirth
- 1994
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 73:10, s. 779-781
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Journal article (peer-reviewed)abstract
- BACKGROUND. To evaluate the relationship between stillbirth in singleton pregnancy (> or = 28 weeks gestation) and maternal weight (weight gain) from 24 completed weeks. METHODS. All fetal deaths (n = 210) at five delivery units during seven years in southern Sweden were analysed. To each case a control mother was selected, the only matching criteria being parity and place of delivery. Regression analysis was used for comparison of body weight gain in cases and controls. RESULTS. Mothers experiencing stillbirth had a significantly lower mean body weight at 24 weeks gestation than control mothers (63.5 kg vs 67.3 kg; t = 2.4, p < 0.05). No significant difference between cases and controls was found in mean weight gain during pregnancy from 24 completed gestational weeks to delivery, even when the last three measurements before delivery for cases and controls were compared separately. CONCLUSION. There is no difference in body weight gain between mothers with stillbirth and mothers giving birth to a live infant.
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- Smits, A, et al.
(author)
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Expression of platelet-derived growth factor in and around intrastriatal embryonic mesencephalic grafts
- 1993
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In: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 2:2, s. 151-162
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Journal article (peer-reviewed)abstract
- The expression of platelet-derived growth factor (PDGF) was investigated in the embryonic donor tissue and surrounding host brain before and after intracerebral transplantation in a rat model of Parkinson's disease (PD). Ventral mesencephalic tissue from E13-E15 rat embryos was dissociated and implanted into adult rats with unilateral lesions of the mesostriatal dopamine system. Immunohistochemical studies showed that the majority of the grafted cells were PDGF-positive at early time points after grafting. However, the immunostaining gradually decreased, and had disappeared almost completely 3 wk after transplantation. These results were in agreement with in situ hybridization data demonstrating detectable levels of mRNA for PDGF chains in graft cells after 1, but not after 6 wk. In contrast, a large number of PDGF-immunoreactive cells was observed in the host brain adjacent to the grafts from 1 wk after transplantation, and increasing with time. Increased expression of PDGF was also observed in response to a sham-operation (injection of vehicle), although the number of PDGF-positive cells seemed lower than after grafting of embryonic tissue. Double immunofluorescence labeling of these cells with an anti-glial fibrillary acidic protein (GFAP) antiserum and a monoclonal antibody against PDGF B-chain, indicated that the PDGF-positive cells were astrocytes. The dynamic expression of PDGF in and around intrastriatal embryonic mesencephalic implants has several, potentially important, implications for graft survival and function. Glial cells could utilize the elevated levels of PDGF to proliferate in a reactive gliosis, and PDGF might also augment immune responses. It is also possible that PDGF increases the survival of, and promotes neurite outgrowth from, grafted dopaminergic neurons.
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- Walles, Bengt, et al.
(author)
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Maternal health care program and markers for late fetal death
- 1994
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 73:10, s. 773-778
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Journal article (peer-reviewed)abstract
- OBJECTIVE. To identify markers for late fetal death, a multicenter study was performed, based on routinely obtained data from maternal health care units. MATERIAL AND METHODS. Prospectively recorded data were obtained from maternal health care units belonging to five delivery units. In all, 233 consecutive cases of singleton pregnancy involving late fetal death (> or = 28 weeks) were identified between 1983 and 1989. As a control for each case, the next consecutive mother giving birth to a live infant at the same delivery unit was selected, the sole matching criterium being parity. RESULTS. After exclusion of pregnancies with lethal malformations or trauma, 205 cases remained for the statistical analysis. Two main subgroups were identified: mothers with placental abruption (n = 44), and pregnancies with no obvious reason for fetal death (n = 101). An increased risk for late fetal death was evident in expectant mothers > or = 40 years (10 vs 1; chi 2 = 7.6, p < 0.01), and in smokers where an association was seen to placental abruption. A significantly increased risk was also seen in women with medical treatment for essential hypertension (8 vs 1; chi 2 = 5.6, p < 0.05). On the other hand, we found no correlation between proteinuria, glucosuria, decreasing symphysis-fundal height, or changes in the Hb, on the one hand, and late fetal demise, on the other. There was no overrepresentation of post dated pregnancy (by ultrasound early in the second trimester) among the cases. Nor did post dated pregnancies (> or = 42 weeks) estimated from first day of last menstrual period (but not post dated by ultrasound) imply a higher rate of fetal death, as has been suggested in previous studies. CONCLUSION. In the present material, there was no sign of systematic error in the evaluation of data routinely obtained from the antenatal clinics and maternity units. Apart from placental abruption in smokers, a high maternal age, and medical treatment for essential hypertension, deviating data were recorded as often among controls as among cases. No correlation was evident between a post date pregnancy and fetal demise. A short symphysis-fundal height was recorded as often among controls as among cases and the even distribution of fetal birthweight in case pregnancies around the standard curve for the normal population is noteworthy.
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| 10. |
- Yuan, S, et al.
(author)
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Effect of dofetilide on cardiac repolarization in patients with ventricular tachycardia. A study using simultaneous monophasic action potential recordings from two sites in the right ventricle
- 1994
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In: European Heart Journal. - 0195-668X. ; 15:4, s. 22-514
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Journal article (peer-reviewed)abstract
- Monophasic action potentials (MAP) were simultaneously recorded from the right ventricular (RV) apex (RVA) and the outflow tract (RVOT) before and after an infusion of dofetilide in 10 patients with documented ventricular tachycardia. After the drug infusion, the MAP duration (MAPd), repolarization time, and corrected QT interval were significantly prolonged during sinus rhythm, RV pacing, and RV extra stimulation. The prolongation of MAPd at 90% repolarization during RV pacing at a cycle length of 500 ms was 31 +/- 6 ms (13%) and 26 +/- 7 ms (11%) at RVA and RVOT, respectively. The ventricular effective refractory period was significantly prolonged by 33 +/- 9 ms (13%) and 22 +/- 7 ms (9%) at driving cycle lengths 600 and 500 ms, respectively. The MAPd shortening with decreasing diastolic time intervals was significantly diminished by dofetilide in early extra beats during RV extra stimulation, suggesting a relatively more pronounced effect of this drug at the early diastolic phase. The dispersion of repolarization, defined as the difference in MAPd between RVA and RVOT, and the activation time were not significantly changed. In conclusion, acute administration of dofetilide in patients with ventricular tachycardia significantly prolonged the time intervals of ventricular repolarization and refractoriness in a parallel fashion, without affecting intraventricular conduction. The effect of dofetilide on MAPd prolongation appeared not to be reverse use-dependent in this study in humans. These results verify the selective class III antiarrhythmic property of dofetilide and warrant further studies in patients.
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