Spinal Muscular Atrophy (SMA), traditionally described as a predominantly childhood form of motor neuron disease, is a leading genetic cause of infant mortality. Although motor neurons are undoubtedly the primary affected cell type, SMA is now widely recognised as a multisystem disorder, where a variety of organs and systems in the body are also affected. Vascular perfusion abnormalities have previously been reported in both patients and mouse models of SMA, however it remains unclear whether these defects are secondary to the motor neuron pathology for which this disease is known. Through analysis of the 'Taiwanese' murine model of severe SMA (Smn-/-;SMN2tg/0, Smn-/+) we report significant vascular defects in the retinas of SMA mice, a tissue devoid of motor neurons, thus providing strong evidence that these vascular defects are independent of motor neuron pathologies. We show that restoration of Smn levels by antisense oligonucleotide treatment at birth significantly ameliorates retinal vascular defects. Next, we report defects in the neural retina, with a significant decrease in key neural cells in SMA mice. A similar vascular pathology was expected in the spleen of SMA mice given that the spleen is small and pale in appearance; however, the density of the intrinsic vasculature remained unchanged. We report that the spleen is disproportionately small in SMA mice, correlated to low levels of cell proliferation, increased cell death, and multiple lacunae. The SMA spleen lacks its distinctive red appearance and presents with a degenerated capsule and a disorganized fibrotic architecture. Histologically distinct white pulp fails to form and this is reflected in an almost complete absence of B lymphocytes necessary for normal immune function. Taken together, these results highlight both the vascular and immune systems as key targets of SMA pathology that should be considered during treatment of this disease.

Thesis (M.F.A.)--Rochester Institute of Technology, 1995. / Typescript. Includes bibliographical references (leaves 55-56).

Thesis (M.Sc.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Medical Physics, Department of Physics. Title from pdf file main screen (viewed on July 17, 2010). Includes bibliographical references.

176 f. / Submitted by Ana Valéria de Jesus Moura (anavaleria_131@hotmail.com) on 2013-08-08T13:06:40Z No. of bitstreams: 1 TACIANA PALMEIRA ANDRADE.pdf: 717253 bytes, checksum: c8857f412a3564ee49e95e9e34112dd5 (MD5) / Approved for entry into archive by Ana Valéria de Jesus Moura(anavaleria_131@hotmail.com) on 2013-08-08T13:12:32Z (GMT) No. of bitstreams: 1 TACIANA PALMEIRA ANDRADE.pdf: 717253 bytes, checksum: c8857f412a3564ee49e95e9e34112dd5 (MD5) / Made available in DSpace on 2013-08-08T13:12:32Z (GMT). No. of bitstreams: 1 TACIANA PALMEIRA ANDRADE.pdf: 717253 bytes, checksum: c8857f412a3564ee49e95e9e34112dd5 (MD5) Previous issue date: 2009 / O presente trabalho tem como objetivo principal demonstrar a possibilidade do ordenamento jurídico brasileiro abarcar a hipótese de escolha pelo doador do destinatário dos seus órgãos na doação de órgãos post mortem. Inicialmente, busca-se enquadrar o direito ao próprio corpo como direito da personalidade, relativizando o caráter de indisponibilidade desses direitos de forma a reconhecer a incidência da autonomia privada em seu campo. Ainda, será analisado o princípio da autonomia na sua concepção bioética e sua influência na determinação da possibilidade da escolha pelo doador de órgãos post mortem. Outrossim, ficará demonstrado que o sistema atual possui falhas e que a compatibilização do modelo atual com a possibilidade de escolha pelo doador é possível,utilizando-se como parâmetro o tratamento dado à doação em vida no direito pátrio, bem como na legislação estrangeira. / Salvador

Indiana University-Purdue University Indianapolis (IUPUI) / The basic Helix-Loop-Helix (bHLH) transcription factors Hand1 and Hand2 play critical roles in the development of multiple organ systems during embryogenesis. The dynamic expression patterns of these two factors within developing tissues obfuscates their respective unique and redundant organogenic functions. To define cell lineages potentially dependent upon Hand gene expression, we generated a mutant allele in which the coding region of Hand1 is replaced by Cre recombinase. Subsequent Cre-mediated activation of β-galactosidase or eYFP reporter alleles enabled lineage trace analyses that clearly define the fate of Hand1-expressing cells. Comparisons between Hand1 expression and Hand1-lineage greatly refine our understanding of its dynamic spatio-temporal expression domains and raise the possibility of novel Hand1 functions in structures not thought to be Hand1-dependent. To genetically examine functional overlap between Hand1 and Hand2, we conditionally deleted Hand2 from Hand1-expressing cells. Hand2 conditional knockout mice die midgestation and exhibit cardiovascular and limb defects. Moreover, Hand2 lineage-restricted deletion from the proepicardial organ results in defective epicardialization and failure to form coronary arteries. Together, these novel data demonstrate a hierarchal relationship whereby transient Hand1 expression within the septum transversum defines epicardial precursors that depend upon subsequent Hand2 function.

A thesis submitted to the faculty of Engineering, University of the Witwatersrand, Johannesburg , in fulfillment of the requirements for the degree of Doctor of Philosophy. Johannesburg, November 1994 / Organ function is often characterised using imaging techniques. In particular a tracer is often used which does not react with tissue, is low in concentration, follows body fluid flows and is distinguishable from the observed system and thus measurable. These requirements ensure linear characteristics of the tracer. In this thesis, these linear characteristics are used to develop a generalised mathematical theory to determine organ function from imaged tracer experiments. The theory is based on anatomical and physiological information for single and multiple input organs. [Abbreviated Abstract. Open document to view full version] / MT2018