Karolinska Institutet

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.

Adipsia and Aphagia after 6-Hydroxydopamine Induced Degeneration of the Nigro-striatal Dopamine System

Abstract: The functional role of the nigro-striatal dopamine (DA) system has been investigated on the basis of a recent detailed mapping of its path and a new method of lesioning the catecholamine systems selectively by intracerebral injection of 6-hydroxydopamine (6-OH-DA). The investigation was especially focused on the symptoms of adipsia, aphagia, hypokinesia and catalepsia after lateral hypothalamic lesions as such lesions may interrupt the ascending DA axons. Electrocoagulations or 6-OH-DA lesions were performed bilaterally at several sites along the DA pathway and the behavioural effects were evaluated in relation to the histochemically detected lesion of the DA pathway. It was concluded that bilateral complete degeneration of the nigro-striatal DA pathway produces severe, long lasting adipsia and aphagia, hypoactivity, difficulties to initiate activity and loss of exploratory behaviour and curiosity. Experiments with DA receptor stimulating and blocking drugs supported the lesion results. Catalepsia and somnolence were attributed to the interruption of other pathways. The results suggest an important role for the nigro-striatal DA system and the striatum in the control of behaviour. A number of symptoms earlier related to the hypothalamus may in fact be due to disturbance of the nigro-striatal DA system.

Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease

Abstract: BACKGROUND: An increased level of Lp(a) lipoprotein has been identified as a risk factor for coronary artery disease that is highly heritable. The genetic determinants of the Lp(a) lipoprotein level and their relevance for the risk of coronary disease are incompletely understood. METHODS: We used a novel gene chip containing 48,742 single-nucleotide polymorphisms (SNPs) in 2100 candidate genes to test for associations in 3145 case subjects with coronary disease and 3352 control subjects. Replication was tested in three independent populations involving 4846 additional case subjects with coronary disease and 4594 control subjects. RESULTS: Three chromosomal regions (6q26-27, 9p21, and 1p13) were strongly associated with the risk of coronary disease. The LPA locus on 6q26-27 encoding Lp(a) lipoprotein had the strongest association. We identified a common variant (rs10455872) at the LPA locus with an odds ratio for coronary disease of 1.70 (95% confidence interval [CI], 1.49 to 1.95) and another independent variant (rs3798220) with an odds ratio of 1.92 (95% CI, 1.48 to 2.49). Both variants were strongly associated with an increased level of Lp(a) lipoprotein, a reduced copy number in LPA (which determines the number of kringle IV-type 2 repeats), and a small Lp(a) lipoprotein size. Replication studies confirmed the effects of both variants on the Lp(a) lipoprotein level and the risk of coronary disease. A meta-analysis showed that with a genotype score involving both LPA SNPs, the odds ratios for coronary disease were 1.51 (95% CI, 1.38 to 1.66) for one variant and 2.57 (95% CI, 1.80 to 3.67) for two or more variants. After adjustment for the Lp(a) lipoprotein level, the association between the LPA genotype score and the risk of coronary disease was abolished. CONCLUSIONS: We identified two LPA variants that were strongly associated with both an increased level of Lp(a) lipoprotein and an increased risk of coronary disease. Our findings provide support for a causal role of Lp(a) lipoprotein in coronary disease.

International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy: Response to Weinert

Abstract: In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort. The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …

Control of Locomotion in Bipeds, Tetrapods, and Fish

Abstract: The sections in this article are: 1 Biomechanical and Electromyographical Information 1.1 Single Limb During Locomotion 1.2 Interlimb Coordination 1.3 Treadmill Versus Overground Locomotion 1.4 Trunk Movements During Locomotion 1.5 Pathological Gaits 1.6 Summary 2 Neural Generation of “Basic Locomotor Synergy” 2.1 Central Versus Peripheral 2.2 Parts of CNS of Primary Importance for Neural Control of Basic Locomotor Synergy 2.3 Spinal Centers for Locomotion—Behavioral Results 2.4 Reflex Control of Basic Locomotor Synergy 2.5 Activity in Certain Spinal, Cerebellar, and Brain Stem Neurons and in Certain Reflex Pathways During Locomotion 2.6 Cerebellum and Locomotion 2.7 Initiation of Locomotion—Brain Stem Circuitry 2.8 Central Organization of Spinal Pattern Generation 2.9 Possible Rhythm-Generating Mechanisms and Models—Facts and Fiction 2.10 Developmental Aspects 2.11 Summary 3 Adapting Basic Locomotor Synergy to Animal's Needs 3.1 Changing Speed 3.2 Goal-Directed Locomotion—Turning and Walking Along Curvatures 3.3 Modifications of “Locomotor Posture” 3.4 Positioning of Limb in Each Step 3.5 Reflex Adaptation of Step 3.6 Summary 4 Concluding Remarks

Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of β-secretase

Abstract: BACE is an enzyme necessary for the generation of neurotoxic amyloid-β in Alzheimer's disease. Claes Wahlestedt and his colleagues identify a noncoding RNA that is upregulated in the brains of individuals with Alzheimer's disase. This noncoding RNA increases expression of BACE, driving amyloid-β generation and possibly disease progression.