Perusinis II. Fall: Der Alzheimer Patient R.M. Geschichte, Genealogie und Genetik eines psychiatriehistorischen Falls

1.American Journal of Alzheimer`s Disease and Other Dementias: 2010; 25:189-192 100th anniversary of PERUSINI`S SECOND CASE: PATIENT RM and his KINDRED Im Jahre 1907 wurde der Münchener Korbmacher RM als ,,Zweifelhafter Fall“ in der damals ,,Königlich Psychiatrischen Klinik“ in München behandelt. Die diesbezüglich 1909 von Alzheimers Assistenten Gaetano Perusini publizierte Kasuistik siedelt den offensichtlichen Symptomausbruch im Jahr 1899 an. Dieser gemutmaßte extrem frühe Krankheitsbeginn (38.Lebensjahr des RM) sowie Perusinis familienanamnestischer Hinweis ,,ein Bruder desselben soll nicht recht gescheut sein“ erforderte intensive Recherche zu Geschichte und Genealogie dieses psychiatriehistorischen Falls, um das eventuelle Vorliegen einer heredofamiliären Form von Morbus Alzheimer mit Beginn im frühen Lebensalter zu diskutieren. Detaillierte Untersuchungen über acht Generationen konnten zwar psychiatrische Auffälligkeiten im Stammbaum des Probanden aufzeigen, aber keinen Nachweis einer autosomal-dominanten Form der “Early-Onset Alzheimer`s Disease“ erbringen. 2.Nervenheilkunde: 2010; 29:850-852 Alzheimer und Perusini: Patient RM und sein Stammbaum 1773-2009 Die ersten vier Fälle der Alzheimerschen Krankheit wurden in Alzheimers histopathologischem Laboratorium von dem italienischen Neuropathologen Gaetano Perusini untersucht. Das Weiterverfolgen von Perusinis Hinweis zur auffälligen Psychopathologie des Bruders des RM zeigt noch 1923 die identische differentialdiagnostische Überlegung „Arteriosklerose“ wie bereits 1907 beim Probanden selbst. Das Nachvollziehen der damals angewandten relevanten Untersuchungsmethoden zur Sicherung der Verdachtsdiagnose „Progressive Paralyse“ weist erhebliche Ungenauigkeiten in der Dokumentation auf, so dass verschiedene Differentialdiagnosen zu diskutieren sind. Kurz vor ihrem Tod konnte eine APOE-Genotypisierung der gemäß nervenärztlicher Diagnose an dementiellem Syndrom erkrankten Enkeltochter von Perusinis II.Fall durchgeführt werden. Die Genotypisierung konnte das Vorliegen einer autosomal-dominanten Form des Morbus Alzheimer mit frühem Beginn nicht belegen. 3.Nervenarzt: 2011; 82:363-368 La malattia di Alzheimer-Perusini: Zum 100. Jahrestag der Publikation Gaetano Perusinis Die Arbeit zielt ab auf Honorierung der Verdienste des Wissenschaftlers Gaetano Perusini (1879-1915). Durch seine genau ein Jahrhundert zurückliegende Veröffentlichung ,,Über klinisch und histologisch eigenartige psychische Erkrankungen des späteren Lebensalters“ kann er als Wegbereiter für das moderne Konzept des altersunspezifischen Beginns der Alzheimerschen Krankheit gelten. Gaetano Perusini arbeitete wissenschaftlich zusammen mit Ugo Cerletti, Alois Alzheimer, Franz Nissl sowie Emil Kraepelin und war beteiligt an der Herausgabe der ,,Folia Neurobiologica“. In seinem persönlichen Schicksal spiegelt sich die Tragik des 1.Weltkrieges: An den Folgen seiner Verwundung durch einen Granatsplitter verstarb Gaetano Perusini im Alter von nur 36 Jahren

Fullerene-based Biocomponents : New Concepts For Functionalising Membranes

Lipophilic hexakisadducts of fullerene C60 form unprecedented rod-like nanoaggregates in phospholipid-membrane bilayers, resulting in modification of the micromechanic properties and stabilisation of the membrane. Lipofullerenes with amphiphilic side chains enable additionally derivatisation and molecular recognition at the membrane surface. The amphiphilic spacer acts as a transmembrane anchor and provides the terminal functionality outside of the membrane. New systems derived from parent compound 3 carry two functional groups each and can be easily modified due to the modular synthesis. Terminal functionalities to be investigated include D(+)-biotin and IDA (iminodiacetic acid) ligands, as used in nickel-histidine tags. Modification of the lipophilic region, for instance with unsaturated addends is also possible. These addends should allow polymerisation inside the membrane and potentially lead to a tremendous increase of the membrane rigidity. Furthermore, mono- and bilayer-forming fullerene derivatives without the membrane-forming support of lecithins are investigated and exhibit interesting features

X-Ray Searches for Emission from the WHIM in the Galactic Halo and the Intergalactic Medium

At least 50% of the baryons in the local universe are undetected and predicted to be in a hot dilute phase (1E5-1E7 K) in low and moderate overdensity environments. We searched for the predicted diffuse faint emission through shadowing observations whereby cool foreground gas absorbs more distant diffuse emission. Observations were obtained with Chandra and XMM-Newton. Using the cold gas in two galaxies, NGC 891 and NGC 5907, shadows were not detected and a newer observation of NGC 891 fails to confirm a previously reported X-ray shadow. Our upper limits lie above model predictions. For Local Group studies, we used a cloud in the Magellanic Stream and a compact high velocity cloud to search for a shadow. Instead of a shadow, the X-ray emission was brighter towards the Magellanic Stream cloud and there is a less significant brightness enhancement toward the other cloud also. The brightness enhancement toward the Magellanic Stream cloud is probably due to an interaction with a hot ambient medium that surrounds the Milky Way. We suggest that this interaction drives a shock into the cloud, heating the gas to X-ray emitting temperatures.Comment: 10 ApJ pages with 10 figure

Plasma TF activity predicts cardiovascular mortality in patients with acute myocardial infarction

<p>Abstract</p> <p>Objectives and Background</p> <p>Tissue factor (TF) contributes to thrombosis following plaque disruption in acute coronary syndromes (ACS). Aim of the study was to investigate the impact of plasma TF activity on prognosis in patients with ACS.</p> <p>Methods and Results</p> <p>One-hundred seventy-four patients with unstable Angina pectoris (uAP) and 112 patients with acute myocardial infarction (AMI) were included with a mean follow up time of 3.26 years. On admission, plasma TF activity was assessed. Patients were categorized into 2 groups: a high-TF activity group with TF >24 pmol/L and low TF activity group with TF ≤ 24 pmol/L. Fifteen cardiovascular deaths occurred in the uAP group and 16 in the AMI group. In AMI TF activity was 24,9 ± 2,78 pmol/l (mean ± SEM) in survivors and 40,9 ± 7,96 pmol/l in nonsurvivors (P = 0.024). In uAP no differences were observed (25.0 ± 8.04 pmol/L nonsurvivors vs. 25.7 ± 2.14 pmol/L survivors; P = 0.586). Kaplan-Meier estimates of survival at 3.26 years regarding TF activity in AMI were 81.3% and 92.2% with an hazard ratio of 3.02 (95% CI [1.05–8.79], P = 0.03). The Cox proportional hazards model adjusting for correlates of age and risk factors showed that plasma TF activity was an independent correlate of survival (hazard ratio 9.27, 95% CI [1.24–69.12], P = 0.03). In an additional group of patients with uAP and AMI, we identified circulating microparticles as the prevailing reservoir of plasma TF activity in acute coronary syndromes.</p> <p>Conclusion</p> <p>Systemic TF activity in AMI has an unfavorable prognostic value and as a marker for dysregulated coagulation may add to predict the atherothrombotic risk.</p

Myc regulates keratinocyte adhesion and differentiation via complex formation with Miz1

Myc plays a key role in homeostasis of the skin. We show that Miz1, which mediates Myc repression of gene expression, is expressed in the epidermal basal layer. A large percentage of genes regulated by the Myc–Miz1 complex in keratinocytes encode proteins involved in cell adhesion, and some, including the α6 and β1 integrins, are directly bound by Myc and Miz1 in vivo. Using a Myc mutant deficient in Miz1 binding (MycV394D), we show that Miz1 is required for the effects of Myc on keratinocyte responsiveness to TGF-β. Myc, but not MycV394D, decreases keratinocyte adhesion and spreading. In reconstituted epidermis, Myc induces differentiation and loss of cell polarization in a Miz1-dependent manner. In vivo, overexpression of β1 integrins restores basal layer polarity and prevents Myc-induced premature differentiation. Our data show that regulation of cell adhesion is a major function of the Myc–Miz1 complex and suggest that it may contribute to Myc-induced exit from the epidermal stem cell compartment

Transcriptional properties of human NANOG1 and NANOG2 in acute leukemic cells

Transcripts of NANOG and OCT4 have been recently identified in human t(4;11) leukemia and in a model system expressing both t(4;11) fusion proteins. Moreover, downstream target genes of NANOG/OCT4/SOX2 were shown to be transcriptionally activated. However, the NANOG1 gene belongs to a gene family, including a gene tandem duplication (named NANOG2 or NANOGP1) and several pseudogenes (NANOGP2-P11). Thus, it was unclear which of the NANOG family members were transcribed in t(4;11) leukemia cells. 5′-RACE experiments revealed novel 5′-exons of NANOG1 and NANOG2, which could give rise to the expression of two different NANOG1 and three different NANOG2 protein variants. Moreover, a novel PCR-based method was established that allows distinguishing between transcripts deriving from NANOG1, NANOG2 and all other NANOG pseudogenes (P2–P11). By applying this method, we were able to demonstrate that human hematopoietic stem cells and different leukemic cells transcribe NANOG2. Furthermore, we functionally tested NANOG1 and NANOG2 protein variants by recombinant expression in 293 cells. These studies revealed that NANOG1 and NANOG2 protein variants are functionally equivalent and activate a regulatory circuit that activates specific stem cell genes. Therefore, we pose the hypothesis that the transcriptional activation of NANOG2 represents a ‘gain-of-stem cell function’ in acute leukemia

Acute kidney injury and tools for risk-stratification in 456 patients with hantavirus-induced nephropathia epidemica

BACKGROUND Puumala virus (PUUV) is the most common species of hantavirus in Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by acute kidney injury (AKI) and thrombocytopenia. The major goals of this study were to provide a clear clinical phenotyping of AKI in patients with NE and to develop an easy prediction rule to identify patients, who are at lower risk to develop severe AKI. METHODS A cross-sectional prospective survey of 456 adult patients with serologically confirmed NE was performed. Data were collected from medical records and prospectively at follow-up visit. Severe AKI was defined by standard criteria according to the RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) classification. Fuller statistical models were developed and validated to estimate the probability for severe AKI. RESULTS During acute NE, 88% of the patients had AKI according to the RILFE criteria during acute NE. A risk index score for severe AKI was derived by using three independent risk factors in patients with normal kidney function at time of diagnosis: thrombocytopenia [two points; odds ratios (OR): 3.77; 95% confidence intervals (CI): 1.82, 8.03], elevated C-reactive protein levels (one point; OR: 3.02; 95% CI: 1.42, 6.58) and proteinuria (one point; OR: 3.92; 95% CI: 1.33, 13.35). On the basis of a point score of one or two, the probability of severe AKI was 0.18 and 0.28 with an area under the curve of 0.71. CONCLUSION This clinical prediction rule provides a novel and diagnostically accurate strategy for the potential prevention and improved management of kidney complications in patients with NE and, ultimately, for a possible decrease in unnecessary hospitalization in a high number of patient