Karolinska Institutet

About: Karolinska Institutet is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Poison control. The organization has 46212 authors who have published 121142 publications receiving 6008130 citations.

The emerging biology of the nitrite anion

Abstract: Nitrite has now been proposed to play an important physiological role in signaling, blood flow regulation and hypoxic nitric oxide homeostasis. A recent two-day symposium at the US National Institutes of Health highlighted recent advances in the understanding of nitrite biochemistry, physiology and therapeutics.

Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus.

Abstract: TREX1 acts in concert with the SET complex in granzyme A–mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutieres syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3′ UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 × 10−7). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE.

Molecular architecture of the mouse nervous system

Abstract: The mammalian nervous system executes complex behaviors controlled by specialised, precisely positioned and interacting cell types. Here, we used RNA sequencing of half a million single cells to create a detailed census of cell types in the mouse nervous system. We mapped cell types spatially and derived a hierarchical, data-driven taxonomy. Neurons were the most diverse, and were grouped by developmental anatomical units, and by the expression of neurotransmitters and neuropeptides. Neuronal diversity was driven by genes encoding cell identity, synaptic connectivity, neurotransmission and membrane conductance. We discovered several distinct, regionally restricted, astrocytes types, which obeyed developmental boundaries and correlated with the spatial distribution of key glutamate and glycine neurotransmitters. In contrast, oligodendrocytes showed a loss of regional identity, followed by a secondary diversi cation. The resource presented here lays a solid foundation for understanding the molecular architecture of the mammalian nervous system, and enables genetic manipulation of specific cell types.

Extended abdominoperineal resection with gluteus maximus flap reconstruction of the pelvic floor for rectal cancer.

Abstract: Background: Intraoperative tumour perforation, positive tumour margins, wound complications and local recurrence are frequent difficulties with conventional abdominoperineal resection (APR) for rectal cancer. An alternative technique is the extended posterior perineal approach with gluteus maximus flap reconstruction of the pelvic floor. The aim of this study was to report the technique and early experience of extended APR in a select cohort of patients. Methods: The principles of operation are that the mesorectum is not dissected off the levator muscles, the perineal dissection is done in the prone position and the levator muscles are resected en bloc with the anus and lower rectum. The perineal defect is reconstructed with a gluteus maximus flap. Between 2001 and 2005, 28 patients with low rectal cancer were treated accordingly at the Karolinska Hospital. Results: Two patients had ypT0 tumours, 20 ypT3 and six ypT4 tumours. Bowel perforation occurred in one, the circumferential resection margin (CRM) was positive in two, and four patients had local perineal wound complications. Two patients developed local recurrence after a median follow-up of 16 months. Conclusion: The extended posterior perineal approach with gluteus maximus flap reconstruction in APR has a low risk of bowel perforation, CRM involvement and local perineal wound complications. The rate of local recurrence may be lower than with conventional APR. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.