SATELLITED CHROMOSOMES

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32108/1/0000158.pd

Coagulation Studies After Transfusion of Hydroxyethyl Starch Protected Frozen Blood in Primates

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72864/1/j.1537-2995.1974.tb04500.x.pd

The preservation of erythrocytes at liquid nitrogen temperatures with hydroxyethyl starch: the removal of hydroxyethyl starch from erythrocytes after thawing

Packed human erythrocytes were frozen in liquid nitrogen using hydroxyethyl starch as a cryoprotective agent. Upon thawing, the cells were washed with a balanced salt solution. The washed cells were stable when resuspended in 0.154 n NaCl. The postthaw saline stability approximated the total recovery after washing the cells. Intracellular potassium loss was 15% immediately postthaw, and an additional 15% loss occurred after washing. These results indicate that HES can be removed from frozen-thawed cells by washing, and that freezing erythrocytes protected by HES does not result in significant losses of intracellular potassium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33516/1/0000014.pd

Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis

Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets

Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis

Objective Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets. Design Extensive phosphoprotein analysis by reverse phase protein microarrays was performed in AH (n=12) and normal human livers (n=7). Ribosomal S6 kinase (p90RSK) hepatic expression was assessed by qPCR, Western blot and immunohistochemistry. Kaempferol was used as a selective pharmacological inhibitor of the p90RSK pathway to assess the regulation of experimentally-induced liver fibrosis and injury, using in vivo and in vitro approaches. Results Proteomic analysis identified p90RSK as one of the most deregulated kinases in AH. Hepatic p90RSK gene and protein expression was also upregulated in livers with chronic liver disease. Immunohistochemistry studies showed increased p90RSK staining in areas of active fibrogenesis in cirrhotic livers. Therapeutic administration of kaempferol to carbon tetrachloride-treated mice resulted in decreased hepatic collagen deposition, and expression of profibrogenic and proinflammatory genes, compared to vehicle administration. In addition, kaempferol reduced the extent of hepatocellular injury and degree of apoptosis. In primary hepatic stellate cells, kaempferol and small interfering RNA decreased activation of p90RSK, which in turn regulated key profibrogenic actions. In primary hepatocytes, kaempferol attenuated proapoptotic signalling. Conclusions p90RSK is upregulated in patients with chronic liver disease and mediates liver fibrogenesis in vivo and in vitro. These results suggest that the p90RSK pathway could be a new therapeutic approach for liver diseases characterised by advanced fibrosis

Serum Inflammatory Profile for the Discrimination of Clinical Subtypes in Parkinson's Disease

Background: Blood levels of immune markers have been proposed to discriminate patients with Parkinson's disease (PD) from controls. However, differences between clinical PD subgroups regarding these markers still need to be identified. Objective: To investigate whether clinical phenotypes can be predicted by the assessment of immune marker profiles in the serum of PD patients. Methods: Phenotypes of clinical PD from Tübingen, Germany (n = 145) and Toronto, Canada (n = 90) were defined regarding clinical subtype, disease onset, severity, and progression as well as presence of cognitive and/or autonomic dysfunction. A panel of serum immune markers was assessed using principal component analysis (PCA) and regression models to define the marker(s) that were associated with clinical phenotypes after adjusting for potential confounders. Findings of both centers were compared for validation. Further, a [18F] FEPPA-PET was performed in a group of patients with high and low values of candidate markers for the assessment of in vivo brain microglial activation. Results: Overall, serum immune markers did not cluster to define a pro/anti-inflammatory profile in PCA. Out of 25 markers only IL-12p40 showed a trend to discriminate between PD subgroups in both cohorts which could not be replicated by [18F] FEPPA-PET. Conclusions: Assessment of cytokines in serum does not reliably differentiate clinical PD subtypes. Accompanying subtype-irrelevant inflammation in PD, dual activity, and lack of specificity of the immune markers, the complex function of microglia, probable effects of treatment, disease stage, and progression on inflammation as well as current technical limitations may limit the usefulness of serum immune markers for the differentiation of subtypes

Inflammatory profile in LRRK2-associated prodromal and clinical PD

BACKGROUND There is evidence for a relevant role of inflammation in the pathogenesis of Parkinson's disease (PD). Mutations in the LRRK2 gene represent the most frequent genetic cause for autosomal dominant PD. LRRK2 is highly expressed in macrophages and microglia suggesting an involvement in inflammatory pathways. The objectives are to test (1) whether idiopathic PD and LRRK2-associated PD share common inflammatory pathways or present distinct profiles and (2) whether non-manifesting LRRK2 mutation carriers present with similar aspects of inflammatory profiles as seen in PD-affected patients. METHODS We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium. RESULTS A large proportion of inflammatory markers were gender-dependent. Both PD-affected cohorts showed increased levels of the pro-inflammatory marker fatty-acid-binding protein. Additionally, idiopathic PD but not LRRK2-associated PD patients showed increased levels of the pro-inflammatory marker interleukin-12-p40 as well as the anti-inflammatory species interleukin-10, brain-derived neurotrophic factor, and stem cell factor. Non-manifesting LRRK2 mutation carriers including those with prodromal characteristics of PD presented with control-like inflammatory profiles. CONCLUSIONS Concomitant inflammation seems to be associated with idiopathic and LRRK2-associated PD. Identifying PD patients in whom inflammatory processes play a major role in their pathophysiology might offer a new therapeutic window at least for a subgroup of patients. Since non-manifesting LRRK2 mutation carriers with symptoms of the prodromal phase of PD did not show inflammatory profiles, activation of the immune system seems not an early event in the disease cascade

Serum Inflammatory Profile for the Discrimination of Clinical Subtypes in Parkinson's Disease

Background: Blood levels of immune markers have been proposed to discriminate patients with Parkinson's disease (PD) from controls. However, differences between clinical PD subgroups regarding these markers still need to be identified.Objective: To investigate whether clinical phenotypes can be predicted by the assessment of immune marker profiles in the serum of PD patients.Methods: Phenotypes of clinical PD from Tübingen, Germany (n = 145) and Toronto, Canada (n = 90) were defined regarding clinical subtype, disease onset, severity, and progression as well as presence of cognitive and/or autonomic dysfunction. A panel of serum immune markers was assessed using principal component analysis (PCA) and regression models to define the marker(s) that were associated with clinical phenotypes after adjusting for potential confounders. Findings of both centers were compared for validation. Further, a [18F] FEPPA-PET was performed in a group of patients with high and low values of candidate markers for the assessment of in vivo brain microglial activation.Results: Overall, serum immune markers did not cluster to define a pro/anti-inflammatory profile in PCA. Out of 25 markers only IL-12p40 showed a trend to discriminate between PD subgroups in both cohorts which could not be replicated by [18F] FEPPA-PET.Conclusions: Assessment of cytokines in serum does not reliably differentiate clinical PD subtypes. Accompanying subtype-irrelevant inflammation in PD, dual activity, and lack of specificity of the immune markers, the complex function of microglia, probable effects of treatment, disease stage, and progression on inflammation as well as current technical limitations may limit the usefulness of serum immune markers for the differentiation of subtypes

Évolution et manifestation de la nouvelle esthétique de l’image et de la poétique de la parole dans l’avant-garde russe, exprimée dans les livres d’artistes futuristes

Bien que le futurisme russe, à ses débuts, fût influencé par les futuristes italiens, il évolua d’une manière autonome. Dans le domaine de la littérature, on trouve un grand nombre de groupements futuristes divers, tandis que dans les arts visuels, le soi disant Cubo-futurisme voyait le jour. Le Cubo-futurisme liait des tendances cubistes et futuristes afin de faire advenir une forme singulièrement russe. Les livres futuristes, publiés dans les années 1910, nous montrent la naissance d’une nouvelle esthétique du texte et de l’image ainsi que la rupture avec les anciennes normes littéraires et artistiques. Ceci s’exprime à travers des illustrations, la création d’une nouvelle langue et l’entrelacs de l’image et de la parole. Cet article analyse les commencements du futurisme en Russie à partir de plusieurs livres russes pris comme exemples de cette esthétique nouvelle.Although the Russian Futurist movement was initially influenced by the Italian Futurists, it developed in an independent way. In literature, there had been a number of different futurist groups, whereas in the visual arts, the so-called Cubo-Futurism was established, linking the cubist and futurist tendencies in a singularly Russian form. Futurist books, published in the1910s, show the birth of a new aesthetics of text and image and the break with older literary and artistic norms. This was expressed through illustrations, new language and the affiliation of image and word. This article examines the beginnings of Futurism in Russia and considers a few Futurist books as examples of this new aesthetic