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Vienna, Austria

Schuster C.,Medical University of Vienna | Mildner M.,Medical University of Vienna | Botta A.,Medical University of Vienna | Nemec L.,Medical University of Vienna | And 8 more authors.
American Journal of Pathology | Year: 2015

Blood and lymphatic vessels provide nutrients for the skin and fulfill important homeostatic functions, such as the regulation of immunologic processes. In this study, we investigated the development of blood and lymphatic endothelial cells in prenatal human skin in situ using multicolor immunofluorescence and analyzed angiogenic molecules by protein arrays of lysates and cell culture supernatants. We found that at 8 to 10 weeks of estimated gestational age, CD144+ vessels predominantly express the venous endothelial cell marker PAL-E, whereas CD144+PAL-E- vessels compatible with arteries only appear at the end of the first trimester. Lymphatic progenitor cells at 8 weeks of estimated gestational age express CD31, CD144, Prox1, and temporary PAL-E. At that developmental stage not all lymphatic progenitor cells express podoplanin or Lyve-1, which are acquired with advancing gestational age in a stepwise fashion. Already in second-trimester human skin, the phenotype of blood and lymphatic vessels roughly resembles the one in adult skin. The expression pattern of angiogenic molecules in lysates and cell culture supernatants of prenatal skin did not reveal the expected bent to proangiogenic molecules, indicating a complex regulation of angiogenesis during ontogeny. In summary, this study provides enticing new insights into the development and phenotypic characteristics of the vascular system in human prenatal skin. © 2015 American Society for Investigative Pathology.

Schuster C.,Medical University of Vienna | Mildner M.,Medical University of Vienna | Mairhofer M.,Medical University of Vienna | Bauer W.,Medical University of Vienna | And 7 more authors.
Development (Cambridge) | Year: 2014

Despite intense efforts, the exact phenotype of the epidermal Langerhans cell (LC) precursors during human ontogeny has not been determined yet. These elusive precursors are believed to migrate into the embryonic skin and to express primitive surface markers, including CD36, but not typical LC markers such as CD1a, CD1c and CD207. The aim of this study was to further characterize the phenotype of LC precursors in human embryonic epidermis and to compare it with that of LCs in healthy adult skin. We found that epidermal leukocytes in first trimester human skin are negative for CD34 and heterogeneous with regard to the expression of CD1c, CD14 and CD36, thus contrasting the phenotypic uniformity of epidermal LCs in adult skin. These data indicate that LC precursors colonize the developing epidermis in an undifferentiated state, where they acquire the definitive LC marker profile with time. Using a human three-dimensional full-thickness skin model to mimic in vivo LC development, we found that FACS-sorted, CD207- cord bloodderived haematopoietic precursor cells resembling foetal LC precursors but not CD14+CD16- blood monocytes integrate into skin equivalents, and without additional exogenous cytokines give rise to cells that morphologically and phenotypically resemble LCs. Overall, it appears that CD14- haematopoietic precursors possess a much higher differentiation potential than CD14+ precursor cells. © 2014. Published by The Company of Biologists Ltd.

Fiala C.,Gynmed Ambulatorium
Molecular Cytogenetics | Year: 2013

Background: In 1952 Papanicolaou et al. first diagnosed and graded cervical carcinomas based on individual "abnormal DNA contents" and cellular phenotypes. Surprisingly current papilloma virus and mutation theories of carcinomas do not mention these individualities. The viral theory holds that randomly integrated, defective genomes of papilloma viruses, which are often untranscribed, cause cervical carcinomas with unknown cofactors 20-50 years after infection. Virus-free carcinomas are attributed to mutations of a few tumor-suppressor genes, especially the p53 gene. But the paradox of how a few mutations or latent defective viral DNAs would generate carcinomas with endless individual DNA contents, degrees of malignancies and cellular phenotypes is unsolved. Since speciation predicts individuality, we test here the theory that cancers are autonomous species with individual clonal karyotypes and phenotypes. This theory postulates that carcinogens induce aneuploidy. By unbalancing mitosis genes aneuploidy catalyzes chain reactions of karyotypic evolutions. Most such evolutions end with non-viable karyotypes but a few become new cancer karyotypes. Despite congenitally unbalanced mitosis genes cancer karyotypes are stabilized by clonal selections for cancer-specific autonomy. Results: To test the prediction of the speciation theory that individual carcinomas have individual clonal karyotypes and phenotypes, we have analyzed here the phenotypes and karyotypes of nine cervical carcinomas. Seven of these contained papilloma virus sequences and two did not. We determined phenotypic individuality and clonality based on the morphology and sociology of carcinoma cells in vitro. Karyotypic individuality and clonality were determined by comparing all chromosomes of 20 karyotypes of carcinomas in three-dimensional arrays. Such arrays list chromosome numbers on the x-axis, chromosome copy numbers on the y-axis and the number of karyotypes arrayed on the z-axis. We found (1) individual clonal karyotypes and phenotypes in all nine carcinomas, but no virus-specific markers, (2) 1-to-1 variations between carcinoma-specific karyotypes and phenotypes, e.g. drug-resistance and cell morphology, (3) proportionality between the copy numbers of chromosomes and the copy numbers of hundreds of over- and under-expressed mRNAs, (4) evidence that tobacco-carcinogens induce cervical carcinomas via aneuploidy, consistent with the speciation theory. Conclusions: Since the individual clonal karyotypes of nine carcinomas correlated and co-varied 1-to-1 with complex individual transcriptomes and phenotypes, we have classical genetic and functional transcriptomic evidence to conclude that these karyotypes encode carcinomas - much like the clonal karyotypes that encode conventional species. These individual karyotypes explain the individual "DNA contents", the endless grades of malignancies and the complex individual transcriptomes and phenotypes of carcinomas. © 2013 McCormack et al.; licensee BioMed Central Ltd.

Nappi R.E.,University of Pavia | Fiala C.,Gynmed Ambulatorium | Fiala C.,Karolinska Institutet | Chabbert-Buffet N.,University Pierre and Marie Curie | And 6 more authors.
European Journal of Contraception and Reproductive Health Care | Year: 2016

Objectives: Our aim was to assess the level of inconvenience associated with monthly bleeding, determine how many women would prefer a bleeding frequency of less than once a month, and what would motivate their choice. Methods: A 15-min quantitative online survey was carried out among 2883 women aged between 18 and 45 years in six European countries (Austria, Belgium, France, Italy, Poland and Spain). Results: Of those surveyed, 1319 women used a combined hormonal contraceptive (CHC group) and 1564 used a non-hormonal contraceptive or no contraceptive (non-HC group). The menstrual period was significantly longer (5 vs. 4.5 days), heavier (16% vs. 8% heavy menstrual flow) and associated with more symptoms (6.1 vs. 5.6) in non-HC users than in CHC users (p < 0.0001). More than half of the women in each group reported pelvic pain, bloating/swelling, mood swings and irritability, but the rate was significantly higher in the non-HC group. Given the choice, 57% of women in both groups said they would opt for longer intervals between periods. Sexuality, social life, work and sporting activities were key factors affecting their decision. Conclusions: The majority of women would prefer to have menstrual periods less than once a month, with a frequency ranging from once every 3 months to no periods at all. This can be explained by the desire to avoid the unpleasant aspects of menstruation and its negative impact on private and professional life. © 2016 The European Society of Contraception and Reproductive Health.

Duesberg P.H.,University of California at Berkeley | Mandrioli D.,University of California at Berkeley | McCormack A.,University of California at Berkeley | Nicholson J.M.,Virginia Polytechnic Institute and State University | And 4 more authors.
Italian Journal of Anatomy and Embryology | Year: 2011

Summary Since the discoveries of a putative AIDS virus in 1984 and of millions of asymptomatic carriers in subsequent years, no general AIDS epidemic has occurred by 2011. In 2008, however, it has been proposed that between 2000 and 2005 the new AIDS virus, now called HIV, had killed 1.8 million South Africans at a steady rate of 300,000 per year and that anti-HIV drugs could have saved 330,000 of those. Here we investigate these claims in view of the paradoxes that HIV would cause a general epidemic in Africa but not in other continents, and a steady rather than a classical bell-shaped epidemic like all other new pathogenic viruses. Surprisingly, we found that South Africa attributed only about 10,000 deaths per year to HIV between 2000 and 2005 and that the South African population had increased by 3 million between 2000 and 2005 at a steady rate of 500,000 per year. This gain was part of a monotonic growth trajectory spanning from 29 million in 1980 to 49 million in 2008. During the same time Uganda increased from 12 to 31 million, and Sub-Saharan Africa as a whole doubled from 400 to 800 million, despite high prevalence HIV. We deduce from this demographic evidence that HIV is not a new killer virus. Based on a review of the known toxicities of antiretroviral drugs we like to draw the attention of scientists, who work in basic and clinical medical fields, including embryologists, to the need of rethinking the risk-and-benefit balance of antiretroviral drugs for pregnant women, newborn babies and all others who carry antibodies against HIV. © 2011 Firenze University Press.

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