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Sebastian Gidlöf

Other affiliations: Karolinska University Hospital
Bio: Sebastian Gidlöf is an academic researcher from Karolinska Institutet. The author has contributed to research in topics: Population & Pregnancy. The author has an hindex of 14, co-authored 32 publications receiving 2792 citations. Previous affiliations of Sebastian Gidlöf include Karolinska University Hospital.

Papers
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Journal ArticleDOI
27 May 2004-Nature
TL;DR: The results provide a causative link between mtDNA mutations and ageing phenotypes in mammals by creating homozygous knock-in mice that express a proof-reading-deficient version of PolgA, the nucleus-encoded catalytic subunit of mtDNA polymerase.
Abstract: Point mutations and deletions of mitochondrial DNA (mtDNA) accumulate in a variety of tissues during ageing in humans, monkeys and rodents. These mutations are unevenly distributed and can accumulate clonally in certain cells, causing a mosaic pattern of respiratory chain deficiency in tissues such as heart, skeletal muscle and brain. In terms of the ageing process, their possible causative effects have been intensely debated because of their low abundance and purely correlative connection with ageing. We have now addressed this question experimentally by creating homozygous knock-in mice that express a proof-reading-deficient version of PolgA, the nucleus-encoded catalytic subunit of mtDNA polymerase. Here we show that the knock-in mice develop an mtDNA mutator phenotype with a threefold to fivefold increase in the levels of point mutations, as well as increased amounts of deleted mtDNA. This increase in somatic mtDNA mutations is associated with reduced lifespan and premature onset of ageing-related phenotypes such as weight loss, reduced subcutaneous fat, alopecia (hair loss), kyphosis (curvature of the spine), osteoporosis, anaemia, reduced fertility and heart enlargement. Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals.

2,429 citations

Journal ArticleDOI
TL;DR: It is suggested that, contrary to current belief, boys and girls with salt-wasting congenital adrenal hyperplasia were equally missed clinically, and neonatal screening improved detection of the salt-Wasting form in girls as well as boys, saving lives in both sexes.

149 citations

Journal ArticleDOI
TL;DR: Screening for CAH was highly effective in detecting the salt-wasting form and thereby reducing mortality and the sensitivity was negatively correlated with the duration of follow-up.
Abstract: Importance Recent reports have questioned the rationale for neonatal screening for congenital adrenal hyperplasia (CAH) owing to low sensitivity in salt-wasting forms and a high rate of recall (ie, a positive finding resulting in a visit to a pediatrician and a second test) in preterm infants. Objective To determine the efficiency of the neonatal screening program for CAH in Sweden over time. Design, Setting, and Participants Longitudinal prospective population-based study in Sweden. We assessed neonatal screening for CAH from January 1, 1986, through December 31, 2011, when 2 737 932 infants (99.8%) underwent testing. The CYP21A2 genotype was investigated in 219 cases with true-positive findings (94.8%). We investigated the screening outcomes for 231 patients who had true-positive findings, 43 with late diagnosis, and 1497 infants with false-positive findings. Main Outcomes and Measures Sensitivity of the screening for salt-wasting CAH. The most important secondary outcome measures were the positive predictive values and recall rates for full-term and preterm infants and sensitivity for milder forms of CAH. Results A total of 143 patients with salt-wasting CAH were identified; none were missed. The sensitivity was lower for milder forms of the disorder ( P = .04), including 79.7% for simple virilizing forms and 32.4% for nonclassic forms. The positive predictive value was higher in full-term (25.1%) than preterm (1.4%) infants and correlated with gestational age ( r = 0.98; P P P = .03). Conclusions and Relevance Screening for CAH was highly effective in detecting the salt-wasting form and thereby reducing mortality. Additional late-onset cases of CAH were detected in childhood and adolescence, reducing the sensitivity for milder forms. The positive predictive value was high despite a low recall rate in full-term infants. Further improvements are necessary to increase the effectiveness of screening among preterm infants.

88 citations

Journal ArticleDOI
TL;DR: Despite a global pandemic, reports on pregnant women with Coronavirus disease 2019 (COVID-19) are few so far, testing strategies vary substantially and management guidelines are not uniform.
Abstract: Despite a global pandemic, reports on pregnant women with Coronavirus disease 2019 (COVID-19) are few so far, testing strategies vary substantially and management guidelines are not uniform.

85 citations

Journal ArticleDOI
TL;DR: In this article, the authors studied the differentiation of human uterine natural killer cells (uNK cells) in a tissue undergoing constant regeneration and represented the major leukocyte population at the maternal-fetal interface.
Abstract: Immune cell differentiation is critical for adequate tissue-specific immune responses to occur. Here, we studied differentiation of human uterine natural killer cells (uNK cells). These cells reside in a tissue undergoing constant regeneration and represent the major leukocyte population at the maternal-fetal interface. However, their physiological response during the menstrual cycle and in pregnancy remains elusive. By surface proteome and transcriptome analysis as well as using humanized mice, we identify a differentiation pathway of uNK cells in vitro and in vivo with sequential acquisition of killer cell immunoglobulin-like receptors and CD39. uNK cell differentiation occurred continuously in response to the endometrial regeneration and was driven by interleukin-15. Differentiated uNK cells displayed reduced proliferative capacity and immunomodulatory function including enhanced angiogenic capacity. By studying human uterus transplantation and monozygotic twins, we found that the uNK cell niche could be replenished from circulation and that it was under genetic control. Together, our study uncovers a continuous differentiation pathway of human NK cells in the uterus that is coupled to profound functional changes in response to local tissue regeneration and pregnancy.

45 citations


Cited by
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Journal ArticleDOI
06 Jun 2013-Cell
TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.

9,980 citations

Journal ArticleDOI
21 Jul 1979-BMJ
TL;DR: It is suggested that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units, outpatients, and referrals to social services, but for house doctors to assess overdoses would provide no economy for the psychiatric or social services.
Abstract: admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

4,497 citations

Journal ArticleDOI
25 Feb 2005-Cell
TL;DR: The evidence is reviewed that both supports and conflicts with the free radical theory of aging and the growing link between mitochondrial metabolism, oxidant formation, and the biology of aging is examined.

3,870 citations

Journal ArticleDOI
TL;DR: The mitochondria provide a direct link between the authors' environment and their genes and the mtDNA variants that permitted their forbears to energetically adapt to their ancestral homes are influencing their health today.
Abstract: Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the agerelated diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.

3,016 citations

Journal ArticleDOI
16 Mar 2012-Cell
TL;DR: This work provides a current view of how mitochondrial functions impinge on health and disease and identifies mitochondrial dysfunction as a key factor in a myriad of diseases, including neurodegenerative and metabolic disorders.

2,266 citations