From diarrhea to obesity in prohormone convertase 1/3 deficiency: age-dependent clinical, pathologic, and enteroendocrine characteristics

GOALS The aim of this report is to delineate the clinical, pathologic, and enteroendocrine (EE) features of prohormone convertase 1/3 (PC1/3) deficiency in children. BACKGROUND Prohormone convertases play a pivotal role in the activation of biologically inactive hormones. Congenital defects in the EE axis, such as PC1/3 deficiency, have been rarely reported and their pathophysiological mechanisms are largely unknown. STUDY EE function and pathology was evaluated in 4 males (1, 2, 7, and 10 y old) from 2 families with PC1/3 deficiency at a university children's hospital. Clinical course, pathology analysis including immunohistochemistry for PC1/3, PC2, and glucagon-like peptide 1 (GLP-1) and electron microscopy, as well as EE function tests (GLP-1, GLP-2, oral glucose tolerance test) were performed. RESULTS All (n=4) suffered from congenital severe diarrhea associated with malabsorption. The diarrhea improved during the first year of life and hyperphagia with excessive weight gain (BMI>97th percentile) became the predominant phenotype at an older age. Analysis of the enteroendocrine axis revealed high proinsulin levels (57 to 1116 pmol/L) in all patients, low serum GLP-2 levels, and impaired insulin and GLP-1 secretion after an oral glucose tolerance test at a young age, with improvement in 1 older child tested. Electron microscopy showed normal ultrastructure of enterocytes and EE cells. Immunohistochemistry revealed normal expression of chromogranin A, a marker of EE cells but markedly reduced immunostaining for PC1/3 and PC2 in all patients. CONCLUSIONS PC1/3 deficiency is associated with an age dependent, variable clinical phenotype caused by severe abnormalities in intestinal and EE functions. Serum level of proinsulin can be used as an effective screening tool.

What does your neighbourhood say about you? A study of life expectancy in 1.3 million Swiss neighbourhoods

BACKGROUND Switzerland had the highest life expectancy at 82.8 years among the Organisation for Economic Co-operation and Development (OECD) countries in 2011. Geographical variation of life expectancy and its relation to the socioeconomic position of neighbourhoods are, however, not well understood. METHODS We analysed the Swiss National Cohort, which linked the 2000 census with mortality records 2000-2008 to estimate life expectancy across neighbourhoods. A neighbourhood index of socioeconomic position (SEP) based on the median rent, education and occupation of household heads and crowding was calculated for 1.3 million overlapping neighbourhoods of 50 households. We used skew-normal regression models, including the index and additionally marital status, education, nationality, religion and occupation to calculate crude and adjusted estimates of life expectancy at age 30 years. RESULTS Based on over 4.5 million individuals and over 400 000 deaths, estimates of life expectancy at age 30 in neighbourhoods ranged from 46.9 to 54.2 years in men and from 53.5 to 57.2 years in women. The correlation between life expectancy and neighbourhood SEP was strong (r=0.95 in men and r=0.94 women, both p values <0.0001). In a comparison of the lowest with the highest percentile of neighbourhood SEP, the crude difference in life expectancy from skew-normal regression was 4.5 years in men and 2.5 years in women. The corresponding adjusted differences were 2.8 and 1.9 years, respectively (all p values <0.0001). CONCLUSIONS Although life expectancy is high in Switzerland, there is substantial geographical variation and life expectancy is strongly associated with the social standing of neighbourhoods.

Mus Hs 750/4 - Horn=musik : für Parsetthorn, 3 Horn, Trombone basso, Flauto ; desgleichen Trio-, Quartett

[Carl Oestreich]

Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands

4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells.

Moses von Mohl, geboren in Schwaben, 39 3/4 Jahr alt

Welsch (Projektbearbeiter): Karikierende Darstellung eines Moses von Mohl (samt Wappen mit der Aufschrift: "Hony soit qui mal y pense"). Eine Person dieses Namens konnte nicht ermittelt werden; gemeint ist sicherlich der Politiker und spätere Abgeordnete der Frankfurter Nationalversammlung Moriz von Mohl

Ms.Ff.F.Stoltze 3. 4 - Brief von Louis Bareiß und Ludwig Pfau an Friedrich Stoltze

Frankfurter Latern, Papier-Angebot, Ludwig Bareiss

Affetti musici : ne quali si contengono motetti a una, 2, 3, 4, & sei voci ; co'l modo per concertarli nel basso per l'organo

7 Stb.: Canto, Alto, Tenore, Basso, Quinto, Sesta parte, Organo

Na 1 Nachlass Max Horkheimer, 651 - "Vorwort zu Alfred Schmidt: Der Begriff der Natur in der Lehre von Marx"; "Vorlesungen über Autorität und Gesellschaft"; "Über Logik"; "Vorlesungsankündigungen" (p. IX 32.1-3-IX 35)

Vorwort von Horkheimer, Max und Ardorno, Theodor W. zu: Schmidt, Alfred: Der Begriff der Natur in der Lehre Marx. Frankfurt am Main 1962, Frankfurter Beiträge zur Soziologie Band 11. Mehrere Typoskripte und zwei Entwürfe, Typoskrip c mit eigenhändigen Korrekturen von Theodor W. Adorno, 2 Blatt; zweiter Entwurf mit handschriftlichen Korrekturen von Friedrich Pollock, 1 Blatt; Schmidt, Alfred: Gutachten über die Inauguraldissertation 'Die Rolle der Natur in der Marxschen Konzeption der Gesselschaft'. Typoskript mit eigenhändigen Korrekturen, 4 Blatt; Typoskript, 7 Blatt; Pollock, Friedrich: Eigenhändige Notize und Korrekturvorschläge zur Dissertation von Alfred Schmidt, 24 Blatt; Vorlesungen über Autorität und Gesellschaft [Columbia University New York]; 1936-37 "Authority and Status in Modern Society"; 1937-38 "Authoritarian Thought and Institutions in Europe"; 1938-39 "Authoritarian Doctrines and modern European Institutions"; Einleitende Vorlesung über Autorität und Gesellschaft, 1936/37 (Max Horkheimer). Drei englsiche Fassungen, eine deutsche Fassung (GS 12, S.39-68); Zweite Vorlesung über Autorität und Gesellschaft (Max Horkheimer). Englische Fassung, Typoskript mit eigenhändigen Korrekturen, 27 Blatt; deutsche Fassung, Typoskript mit eigenhändigen Korrekturen, 20 Blatt (GS 12, S.39-68); "History" (Herbert Marcuse). Typoskript mit eigenhändigen Korrekturen, 7 Blatt; "Empirical Research" (Paul Lazarfeld). Typoskript, 7 Blatt; "Economica" (Friedrich Pollock). Typoskript, 9 Blatt; "Authoritarian State" (Franz Neumann). Typoskript mit handschriftlichen Korrekturen, 18 Blatt; Teilstück, Typoskript mit handschriftlichen Korrekturen, 1 Blatt; "Education" (Leo Löwenthal ?). Typoskript, 6 Blatt; Einleitung in den psychologischen Teil (Fromm). Englische Fassung, Typoskript, 5 Blatt; Abschlußvorlesung: Zusammenfassung (Max Horkheimer). Englische Fassung, Typoskript mit eigenhändigen und handschriftlichen Korrekturen, 9 Blatt; deutsche Fassung, Typoskript, 5 Blatt (GS 12, S. 39-68); Teilstücke (Entwürfe ?) zu den Vorlesungen. Typoskript mit eigenhändigen Korrekturen, 5 Blatt; Eigenhändige Notizen zu den Vorlesungen, 6 Blatt; Literaturlisten. Als Typoskript vervielfältigt, 3 Blatt; Vorlesungsankündigungen. Als Typoskript vervielfältigt, 4 Blatt; Typoskript, 2 Blatt; Ohne Namen: "Errors in Professor Horkheimers Lecture". Stichworte zu sprachlichen Fehlern Max Horkheimers, 4 Blatt; "Über Logik": Vorlesung von Max Horkheimer, 1939. Typoskript mit handschriftlichen Ergänzungen von Herbert Marcuse, 17 Blatt; Typoskript mit eigenhändigen Korrekturen, 10 Blatt (GS 12, S. 69-74); Vorlesungsankündigungen der Institutsmitglieder (1941 ?); Horkheimer, Max: "The Social Psychology of Mass Movements"; Horkheimer, Max: "Modern Utopias and their Social Background"; Adorno, Theodor W.: "Sociology of Art"; Adorno, Theodor W.: "Sociology of Popular Music"; Marcuse, Herbert: "Social and Intelectual Foundations of Modern European Democracy"; Marcuse, Herbert: "The Development of Social Thought in der Modern Era"; Neumann, Franz: "History of Modern Political Thought"; Neumann, Franz: "Sociology of Legal Institutions"; Löwenthal, Leo: "Sociology of Modern Popular Literature"; Löwenthal, Leo: "Social Trends in European Literature since the Renaissance"; Kirchheimer, Otto: "Sociology of Political Institutions"; Kirchheimer, Otto: "Development of Criminological Thought". Typoskript, 13 Blatt; Typoskript, 7 Blatt; Typoskript mit handschriftlichen Korrekturen, 14 Blatt;