| 441. |
- Steck, Andrea K., et al.
(författare)
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Factors Associated With the Decline of C-Peptide in a Cohort of Young Children Diagnosed With Type 1 Diabetes
- 2021
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:3, s. 1380-1388
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Understanding factors involved in the rate of C-peptide decline is needed to tailor therapies for type 1 diabetes (T1D). OBJECTIVE: Evaluate factors associated with rate of C-peptide decline after a T1D diagnosis in young children. DESIGN: Observational study. SETTING: Academic centers. PARTICIPANTS: A total of 57 participants from the Environmental Determinants of Diabetes in the Young (TEDDY) study who were enrolled at 3 months of age and followed until T1D, and 56 age-matched children diagnosed with T1D in the community. INTERVENTION: A mixed meal tolerance test was used to measure the area under the curve (AUC) C-peptide at 1, 3, 6, 12, and 24 months postdiagnosis. OUTCOME: Factors associated with rate of C-peptide decline during the first 2 years postdiagnosis were evaluated using mixed effects models, adjusting for age at diagnosis and baseline C-peptide. RESULTS: Adjusted slopes of AUC C-peptide decline did not differ between TEDDY subjects and community controls (P = 0.21), although the former had higher C-peptide baseline levels. In univariate analyses combining both groups (n = 113), younger age, higher weight and body mass index z-scores, female sex, an increased number increased number of islet autoantibodies, and IA-2A or ZnT8A positivity at baseline were associated with a higher rate of C-peptide loss. Younger age, female sex, and higher weight z-score remained significant in multivariate analysis (all P < 0.02). At 3 months after diagnosis, higher HbA1c became an additional independent factor associated with a higher rate of C-peptide decline (P < 0.01). CONCLUSION: Younger age at diagnosis, female sex, higher weight z-score, and HbA1c were associated with a higher rate of C-peptide decline after T1D diagnosis in young children.
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| 442. |
- Steck, Andrea K, et al.
(författare)
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Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls
- 2017
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X. ; 18:8, s. 794-802
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore whether children diagnosed with type 1 diabetes during islet autoantibody surveillance through The Environmental Determinants of Diabetes in the Young (TEDDY) study retain greater islet function than children diagnosed through the community. Methods: TEDDY children identified at birth with high-risk human leukocyte antigen and followed every 3months until diabetes diagnosis were compared to age-matched children diagnosed with diabetes in the community. Both participated in long-term follow up after diagnosis. Hemoglobin A1c (HbA1c) and mixed meal tolerance test were performed within 1month of diabetes onset, then at 3, 6, and 12months, and biannually thereafter. Results: Comparison of 43 TEDDY and 43 paired control children showed that TEDDY children often had no symptoms (58%) at diagnosis and none had diabetic ketoacidosis (DKA) compared with 98% with diabetes symptoms and 14% DKA in the controls (P<0.001 and P=0.03, respectively). At diagnosis, mean HbA1c was lower in TEDDY (6.8%, 51mmol/mol) than control (10.5%, 91mmol/mol) children (P<0.0001). TEDDY children had significantly higher area under the curve and peak C-peptide values than the community controls throughout the first year postdiagnosis. Total insulin dose and insulin dose-adjusted A1c were lower throughout the first year postdiagnosis for TEDDY compared with control children. Conclusions: Higher C-peptide levels in TEDDY vs community-diagnosed children persist for at least 12months following diabetes onset and appear to represent a shift in the disease process of about 6months. Symptom-free diagnosis, reduction of DKA, and the potential for immune intervention with increased baseline C-peptide may portend additional long-term benefits of early diagnosis.
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| 443. |
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| 444. |
- Steen, Margareta, et al.
(författare)
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Billigt kött kan stå oss dyrt
- 2015
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Ingår i: Hufvudstadsbladet. - 0356-0724.
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 445. |
- Stehn, Lars, et al.
(författare)
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Project: Lean Wood Engineering
- 2007
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Annan publikation (populärvet., debatt m.m.)abstract
- LWE är ett kompetenscenter för forskning och utveckling inom - industriellt träbyggande, - trämanufaktur samt - interiöra lösningar. LWE är ett samarbete mellan Luleå tekniska universitet (koordinator), Linköpings tekniska högskola, Lunds tekniska högskola, VINNOVA och tolv företag inom bygg- och trämanufaktursektorn. Kompetenscentret involverar ett trettiotal seniora forskare och doktorander.
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| 446. |
- Stenhammar, Christina, et al.
(författare)
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Sexual and contraceptive behavior among female university students in Sweden : repeated surveys over a 25-year period
- 2015
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:3, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo study female students' sexual and contraceptive behavior and compare these results with earlier surveys. DesignComparative, repeated cross-sectional surveys, started in 1989 and repeated every fifth year. SettingContraceptive counseling delivered at a Student Health Center in Sweden. PopulationFemale university students (n=359). MethodsMultiple-choice waiting-room questionnaire. Main outcome measuresSexual and contraceptive behavior. ResultsIn 1989, age at first intercourse was 17.6years vs. 16.7years in 2014, number of lifetime sexual partners was 4.0 vs. 12.1 in 2014, and number of sexual partners during the previous 12months was 1.0 vs. 2.8 in 2014. Condom use during first intercourse with the latest partner decreased from 49% to 41% (n=172 in 2009 vs. n=148 in 2014: p<0.001), and experience of anal sex increased from 39% to 46% (n=136 in 2009 vs. n=165 in 2014: p=0.038), and 25% (n=41 in 2014) always used a condom during anal sex. A total of 70% (n=251) made use of pornography, and 48% (n=121) considered their sexual behavior affected by pornography. Eighty-nine percent (n=291) wanted two to three children and 9% (n=33) had thought about freezing eggs for the future. The female students' knowledge about increasing age being correlated with decreased fertility varied. ConclusionsSexual behavior among female university students has gradually changed during the last 25years and behavior appears more risky today. As this may have consequences on future reproductive health, it is vital to inform women about consistent and correct condom use and about the limitations of the fertile window.
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| 447. |
- Stensman, Helena, et al.
(författare)
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Autophosphorylation suppresses, whereas kinase inhibition augments, the translocation of PKCa in response to diacylglycerol.
- 2004
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 279:39, s. 40576-40583
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Tidskriftsartikel (refereegranskat)abstract
- We have seen that protein kinase Calpha (PKCalpha) is transiently translocated to the plasma membrane by carbachol stimulation of neuroblastoma cells. This is induced by the Ca2+ increase, and PKCalpha does not respond to diacylglycerol (DAG). The unresponsiveness is dependent on structures in the catalytic domain of PKCalpha. This study was designed to investigate if and how the kinase activity and autophosphorylation are involved in regulating the translocation. PKCalpha enhanced green fluorescent protein translocation was studied in living neuroblastoma cells by confocal microscopy. Carbachol stimulation induced a transient translocation of PKCalpha to the plasma membrane and a sustained translocation of kinase-dead PKCalpha. In cells treated with the PKC inhibitor GF109203X, wild-type PKCalpha also showed a sustained translocation. The same effects were seen with PKCbetaI, PKCbetaII, and PKCdelta. Only kinase-dead and not wild-type PKCalpha translocated in response to 1,2-dioctanoylglycerol. To examine whether autophosphorylation regulates relocation to the cytosol, the autophosphorylation sites in PKCalpha were mutated to glutamate, to mimic phosphorylation, or alanine, to mimic the nonphosphorylated protein. After stimulation with carbachol, glutamate mutants behaved like wild-type PKCalpha, whereas alanine mutants behaved like kinase-dead PKCalpha. When the alanine mutants were treated with 1,2-dioctanoylglycerol, all cells showed a sustained translocation of the protein. However, neither carbachol nor GF109203X had any major effects on the level of autophosphorylation, and GF109203X potentiated the translocation of the glutamate mutants. We, therefore, hypothesize that 1) autophosphorylation of PKCalpha limits its sensitivity to DAG and 2) that kinase inhibitors augment the DAG sensitivity of PKCalpha, perhaps by destabilizing the closed conformation.
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| 448. |
- Stensman, Helena, et al.
(författare)
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Identification of acidic amino acid residues in the protein kinase C alpha V5 domain that contribute to its insensitivity to diacylglycerol
- 2007
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 282:39, s. 28627-28638
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Tidskriftsartikel (refereegranskat)abstract
- The protein kinase C (PKC) isoforms are maintained in an inactive and closed conformation by intramolecular interactions. Upon activation these are disrupted by activators, binding proteins and cellular membrane. We have seen that autophosphorylation of two sites in the C-terminal V5 domain is crucial to keep PKC alpha insensitive to the activator diacylglycerol, which presumably is caused by a masking of the diacylglycerol-binding C1a domain. Here we demonstrate that the diacylglycerol sensitivity of the PKC beta isoforms also is suppressed by autophosphorylation of the V5 sites. To analyze conformational differences, a fusion protein ECFP-PKC alpha-EYFP was expressed in cells and the FRET signal was analyzed. The analogous mutant with autophosphorylation sites exchanged for alanine gave rise to a substantially lower FRET signal than wild-type PKC alpha indicating a conformational difference elicited by the mutations. Expression of the isolated PKC alpha V5 domain led to increased diacylglycerol sensitivity of PKC alpha. We identified acidic residues in the V5 domain that, when mutated to alanines or lysines, rendered PKC alpha sensitive to diacylglycerol. Furthermore, mutation to glutamate of four lysines in a lysine-rich cluster in the C2 domain gave a similar effect. Simultaneous reversal of the charges of the acidic residues in the V5 and the lysines in the C2 domain gave rise to a PKC alpha that was insensitive to diacylglycerol. We propose that these structures participate in an intramolecular interaction that maintains PKC alpha in a closed conformation. The disruption of this interaction leads to an unmasking of the C1a domain and thereby increased diacylglycerol sensitivity of PKC alpha.
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| 449. |
- Stensman, Helena, et al.
(författare)
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Protein kinase Cepsilon is important for migration of neuroblastoma cells
- 2008
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Migration is important for the metastatic capacity and thus for the malignancy of cancer cells. There is limited knowledge on regulatory factors that promote the migration of neuroblastoma cells. This study investigates the hypothesis that protein kinase C (PKC) isoforms regulate neuroblastoma cell motility. Methods: PKC isoforms were downregulated with siRNA or modulated with activators and inhibitors. Migration was analyzed with scratch and transwell assays. Protein phosphorylation and expression levels were measured with Western blot. Results: Stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced migration of SK-N-BE(2) C neuroblastoma cells. Treatment with the general protein kinase C (PKC) inhibitor GF109203X and the inhibitor of classical isoforms Go6976 inhibited migration while an inhibitor of PKC beta isoforms did not have an effect. Downregulation of PKC epsilon, but not of PKC alpha or PKC delta, with siRNA led to a suppression of both basal and TPA-stimulated migration. Experiments using PD98059 and LY294002, inhibitors of the Erk and phosphatidylinositol 3-kinase (PI3K) pathways, respectively, showed that PI3K is not necessary for TPA-induced migration. The Erk pathway might be involved in TPA-induced migration but not in migration driven by PKC epsilon. TPA induced phosphorylation of the PKC substrate myristoylated alanine-rich C kinase substrate (MARCKS) which was suppressed by the PKC inhibitors. Treatment with siRNA oligonucleotides against different PKC isoforms before stimulation with TPA did not influence the phosphorylation of MARCKS. Conclusion: PKC epsilon is important for migration of SK-N-BE(2) C neuroblastoma cells. Neither the Erk pathway nor MARCKS are critical downstream targets of PKC epsilon but they may be involved in TPA-mediated migration.
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| 450. |
- Sterner, Y, et al.
(författare)
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Country-specific birth weight and length in type 1 diabetes high-risk HLA genotypes in combination with prenatal characteristics.
- 2011
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Ingår i: Journal of Perinatology. - : Springer Science and Business Media LLC. - 0743-8346 .- 1476-5543. ; 31, s. 764-769
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To examine the relationship between high-risk human leukocyte antigen (HLA) genotypes for type 1 diabetes and birth size in combination with prenatal characteristics in different countries.Study Design:Four high-risk HLA genotypes were enrolled in the Environmental determinants of Diabetes in the Young study newborn babies from the general population in Finland, Germany, Sweden and the United States. Stepwise regression analyses were used to adjust for country, parental physical characteristics and environmental factors during pregnancy.Result:Regression analyses did not reveal differences in birth size between the four type 1 diabetes high-risk HLA genotypes. Compared with DQ 4/8 in each country, (1) DQ 2/2 children were heavier in the United States (P=0.028) mostly explained however, by parental weight; (2) DQ 2/8 (P=0.023) and DQ 8/8 (P=0.046) children were longer in Sweden independent of parents height and as well as (3) in the United States for DQ 2/8 (P=0.023), but again dependent on parental height.Conclusion:Children born with type 1 diabetes high-risk HLA genotypes have comparable birth size. Longitudinal follow-up of these children should reveal whether birth size differences between countries contribute to the risk for islet autoimmunity and type 1 diabetes.Journal of Perinatology advance online publication, 28 April 2011; doi:10.1038/jp.2011.26.
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