| 1. |
- Danfors, Torsten, et al.
(författare)
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Tetrahydrobiopterin in the treatment of children with autistic disorder. A double-blind placebo-controlled crossover study
- 2005
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Ingår i: Journal of Clinical Psychopharmacology. - 0271-0749 .- 1533-712X. ; 25:5, s. 485-489
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Tidskriftsartikel (refereegranskat)abstract
- Twelve children, all boys, aged 4 to 7 years, with a diagnosis of autistic disorder and low concentrations of spinal 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (tetrahydrobiopterin) were selected to participate in a double-blind, randomized, placebo-controlled, crossover study. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during 6 months alternating with placebo. Treatment-induced effects were assessed with the Childhood Autism Rating Scale every third month. The results showed small nonsignificant changes in the total scores of Childhood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis looking at the 3 core symptoms of autism, that is, social interaction, communication, and stereotyped behaviors, revealed a significant improvement of the social interaction score after 6 months of active treatment. In addition, a high positive correlation was found between response of the social interaction score and IQ. The results indicate a possible effect of tetrahydrobiopterin treatment.
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| 2. |
- Hirvonen, M Karoliina, et al.
(författare)
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Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes
- 2023
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.
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| 3. |
- Lavén, Martin, et al.
(författare)
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Determination of flumazenil in human plasma by liquid chromatography - electrospray ionisation tandem mass spectrometry
- 2004
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Ingår i: Journal of Chromatography B. ; :808, s. 221-227
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Tidskriftsartikel (refereegranskat)abstract
- A liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to determine unlabelled flumazenil (Ro 15-1788) in human plasma in (11 C)flumazenil positron emission tomagraphy (PET) studies.N-Methyl tri-deuterated flumazenil was used as an internal standard. The analyte and internal standard were extracted from plasma samples using solid-phase extraction, with a recovery of 78%. This was determined through the convenience of radioactivity measurements of 11 C-labelled flumazenil. The evaporated and reconstituted eluate was analysed by LC-ESI-MS/MS. The calibration curve was linear over the tested concentration range of 0.05-0.5 nM (15-150 pg/ml) with a correlation coefficient, R 2, of 0.998 +- 0.001. A high precision was achieved, with mean intra-assay and inter-assay relative standard deviations of at most 6 and 7%, respectively. The accuracy of the method ranged from 95 to 104%. As a proof of concept, the validated method was applied in the determination of flumazenil in plasma from two healthy volunteers participating in a PET study with three repeated investigations. A bolus-infusion protocol was used to achieve a constant concentration level of flumazenil. The average plasma concentrations ranged from 0.11 and 0.19 nM and all measurements were within the calibration standard range. The flumazenil concentrations were relatively constant within each scan and the average intra-scan precision was 15%.
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| 4. |
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| 5. |
- Moulder, Robert, et al.
(författare)
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A comparative evaluation of software for the analysis of liquid chromatography-tandem mass spectrometry data from isotope coded affinity tag experiments
- 2005
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Ingår i: Proteomics. - : Wiley-VCH Verlagsgesellschaft. - 1615-9853 .- 1615-9861. ; 5:11, s. 2748-2760
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Tidskriftsartikel (refereegranskat)abstract
- The options available for processing quantitative data from isotope coded affinity tag (ICAT) experiments have mostly been confined to software specific to the instrument of acquisition. However, recent developments with data format conversion have subsequently increased such processing opportunities. In the present study, data sets from ICAT experiments, analysed with liquid chromatography/tandem mass spectrometry (MS/MS), using an Applied Biosystems QSTAR Pulsar quadrupole-TOF mass spectrometer, were processed in triplicate using separate mass spectrometry software packages. The programs Pro ICAT, Spectrum Mill and SEQUEST with XPRESS were employed. Attention was paid towards the extent of common identification and agreement of quantitative results, with additional interest in the flexibility and productivity of these programs. The comparisons were made with data from the analysis of a specifically prepared test mixture, nine proteins at a range of relative concentration ratios from 0.1 to 10 (light to heavy labelled forms), as a known control, and data selected from an ICAT study involving the measurement of cytokine induced protein expression in human lymphoblasts, as an applied example. Dissimilarities were detected in peptide identification that reflected how the associated scoring parameters favoured information from the MS/MS data sets. Accordingly, there were differences in the numbers of peptides and protein identifications, although from these it was apparent that both confirmatory and complementary information was present. In the quantitative results from the three programs, no statistically significant differences were observed.
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| 6. |
- Moulder, Robert, et al.
(författare)
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Quantitative proteomics analysis of the nuclear fraction of human CD4+ cells in the early phases of IL-4-induced Th2 differentiation
- 2010
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Ingår i: Molecular & Cellular Proteomics. - : American Society for Biochemistry and Molecular Biology. - 1535-9476 .- 1535-9484. ; 9:9, s. 1937-1953
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Tidskriftsartikel (refereegranskat)abstract
- We used stable isotope labeling with 4-plex iTRAQ (isobaric tags for relative and absolute quantification) reagents and LC-MS/MS to investigate proteomic changes in the nucleus of activated human CD4(+) cells during the early stages of Th2 cell differentiation. The effects of IL-4 stimulation upon activated naïve CD4(+) cells were measured in the nuclear fractions from 6 and 24 h in three biological replicates, each using pooled cord blood samples derived from seven or more individuals. In these analyses, in the order of 800 proteins were detected with two or more peptides and quantified in three biological replicates. In addition to consistent differences observed with the nuclear localization/expression of established human Th2 and Th1 markers, there were changes that suggested the involvement of several proteins either only recently reported or otherwise not known in this context. These included SATB1 and among the novel changes detected and validated an IL-4-induced increase in the level of YB1. This unique data set from human cord blood CD4(+) T cells details an extensive list of protein determinations that compares with and complements previous data determined from the Jurkat cell nucleus.
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