Institution
Karolinska Institutet
Education•Stockholm, Sweden•
About: Karolinska Institutet is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Cancer. The organization has 46212 authors who have published 121142 publications receiving 6008130 citations.
Topics: Population, Cancer, Poison control, Cohort study, Health care
Papers published on a yearly basis
Papers
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TL;DR: The results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD.
Abstract: Gene transfer into hematopoietic stem cells has been used successfully for correcting lymphoid but not myeloid immunodeficiencies. Here we report on two adults who received gene therapy after nonmyeloablative bone marrow conditioning for the treatment of X-linked chronic granulomatous disease (X-CGD), a primary immunodeficiency caused by a defect in the oxidative antimicrobial activity of phagocytes resulting from mutations in gp91(phox). We detected substantial gene transfer in both individuals' neutrophils that lead to a large number of functionally corrected phagocytes and notable clinical improvement. Large-scale retroviral integration site-distribution analysis showed activating insertions in MDS1-EVI1, PRDM16 or SETBP1 that had influenced regulation of long-term hematopoiesis by expanding gene-corrected myelopoiesis three- to four-fold in both individuals. Although insertional influences have probably reinforced the therapeutic efficacy in this trial, our results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD.
1,172 citations
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TL;DR: The standardized RT-PCR protocol and primer sets can now be used for molecular classification of acute leukemia at diagnosis and for MRD detection during follow-up to evaluate treatment effectiveness.
Abstract: Prospective studies on the detection of minimal residual disease (MRD) in acute leukemia patients have shown that large-scale MRD studies are feasible and that clinically relevant MRD-based risk group classification can be achieved and can now be used for designing new treatment protocols. However, multicenter international treatment protocols with MRD-based stratification of treatment need careful standardization and quality control of the MRD techniques. This was the aim of the European BIOMED-1 Concerted Action 'Investigation of minimal residual disease in acute leukemia: international standardization and clinical evaluation' with participants of 14 laboratories in eight European countries (ES, NL, PT, IT, DE, FR, SE and AT). Standardization and quality control was performed for the three main types of MRD techniques, ie flow cytometric immunophenotyping, PCR analysis of antigen receptor genes, and RT-PCR analysis of well-defined chromosomal aberrations. This study focussed on the latter MRD technique. A total of nine well-defined chromosome aberrations with fusion gene transcripts were selected: t(1;19) with E2A-PBX1, t(4;11) with MLL-AF4, t(8;21) with AML1-ETO, t(9;22) with BCR-ABL p190 and BCR-ABL p210, t(12;21) with TEL-AML1, t(15;17) with PML-RARA, inv (16) with CBFB-MYH11, and microdeletion 1p32 with SIL-TAL1. PCR primers were designed according to predefined criteria for single PCR (external primers A B) and nested PCR (internal primers C D) as well as for 'shifted' PCR with a primer upstream (E5' primer) or downstream (E3' primer) of the external A B primers. The 'shifted' E primers were designed for performing an independent PCR together with one of the internal primers for confirmation (or exclusion) of positive results. Various local RT and PCR protocols were compared and subsequently a common protocol was designed, tested and adapted, resulting in a standardized RT-PCR protocol. After initial testing (with adaptations whenever necessary) and approval by two or three laboratories, the primers were tested by all participating laboratories, using 17 cell lines and patient samples as positive controls. This testing included comparison with local protocols and primers as well as sensitivity testing via dilution experiments. The collaborative efforts resulted in standardized primer sets with a minimal target sensitivity of 10-2 for virtually all single PCR analyses, whereas the nested PCR analyses generally reached the minimal target sensitivity of 10-4. The standardized RT-PCR protocol and primer sets can now be used for molecular classification of acute leukemia at diagnosis and for MRD detection during follow-up to evaluate treatment effectiveness.
1,170 citations
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TL;DR: Recommendations are given for the management of patients with acute stone colic and for active removal of stones from the ureter and kidney and the principles for risk evaluation of Patients with recurrent stone formation and appropriate recurrence preventive treatment are given.
1,169 citations
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F. Kyle Satterstrom1, F. Kyle Satterstrom2, Jack A. Kosmicki, Jiebiao Wang3 +198 more•Institutions (53)
TL;DR: The largest exome sequencing study of autism spectrum disorder (ASD) to date, using an enhanced analytical framework to integrate de novo and case-control rare variation, identifies 102 risk genes at a false discovery rate of 0.1 or less, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.
1,169 citations
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TL;DR: Representative samples of mitochondrial and chloroplast targeting peptides have been analyzed in terms of amino acid composition, positional amino acid preferences and amphiphilic character and no highly conserved 'homology blocks' are found in either class of topogenic sequence.
Abstract: Representative samples of mitochondrial and chloroplast targeting peptides have been analyzed in terms of amino acid composition, positional amino acid preferences and amphiphilic character No highly conserved 'homology blocks' are found in either class of topogenic sequence Mitochondrial-matrix-targeting peptides are composed of two domains with different amphiphilic properties Arginine is frequently found either at position -10 or -2 relative to the cleavage site, suggesting that some targeting peptides may be cleaved twice in succession by two different matrix proteases In stroma-targeting chloroplast transit peptides three distinct regions are evident: an uncharged amino-terminal domain, a central domain lacking acidic residues and a carboxy-terminal domain with the potential to form an amphiphilic beta-strand Targeting peptides that route proteins to the mitochondrial intermembrane space or the lumen of chloroplast thylakoids have a mosaic design with an amino-terminal matrix- or stroma-targeting part attached to a carboxy-terminal extension that shares many characteristics with secretory signal peptides
1,168 citations
Authors
Showing all 46522 results
Name | H-index | Papers | Citations |
---|---|---|---|
Meir J. Stampfer | 277 | 1414 | 283776 |
Albert Hofman | 267 | 2530 | 321405 |
Guido Kroemer | 236 | 1404 | 246571 |
Eric B. Rimm | 196 | 988 | 147119 |
Scott M. Grundy | 187 | 841 | 231821 |
Jing Wang | 184 | 4046 | 202769 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
John Hardy | 177 | 1178 | 171694 |
Marc G. Caron | 173 | 674 | 99802 |
Ramachandran S. Vasan | 172 | 1100 | 138108 |
Adrian L. Harris | 170 | 1084 | 120365 |
Douglas F. Easton | 165 | 844 | 113809 |
Zulfiqar A Bhutta | 165 | 1231 | 169329 |
Judah Folkman | 165 | 499 | 148611 |
Ralph A. DeFronzo | 160 | 759 | 132993 |