Typescript. / Thesis (Ph. D.)--University of Hawaii, 1964. / Bibliography: leaves 153-156. / xv, 156 leaves mounted ill., tables

Typescript. / Thesis (Ph. D.)--University of Hawaii, 1966. / Bibliography: leaves 135-139. / vi, 139 l illus

Thesis (M.D.)--University of Adelaide, 1989. / Includes bibliographical references (leaves 107-109).

Peptide nucleic acids (PNAs) were used as encoding tags to enable the analysis of peptide libraries by PNA/DNA hybridisation onto DNA microarrays. This allowed entire peptide libraries to be organised and sorted in a two dimensional format whereby all library members could be interrogated and analysed on a one-byone basis. In this thesis, PNA-encoded peptide libraries, generated by split-and-mix library synthesis, were screened for a variety of functions. Peptide sequences identified from the screening of a PNA-encoded library were analysed in detail as the first specific substrates for chymopapain. A new PNAencoded library consisting of D-amino acids was synthesised and screened with a number of proteases in attempts to identify novel/unusual substrates. PNA-encoded libraries were also used in the screening of peptide libraries for other activities. Thus substrates for catalyst-free Hüisgen cycloaddition were identified following the reaction between an alkyne modified peptide library and azidofluorescein, while cell-penetrating peptides were identified by hybridization of an internalized encoded library onto a DNA microarray.

Bibliography: leaves 107-109.

Bibliography: leaves 107-109 / 109 leaves, [26] leaves of plates : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, 1989

Made available in DSpace on 2015-03-26T13:46:43Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1498735 bytes, checksum: e65541cd95115cdcb1835feee29a3615 (MD5) Previous issue date: 2004-08-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The present study has as objectives to evaluate the clinical-surgical, radiological and histological aspects of canine cervical intervertebral disks after chemonucleolysis with chymopapain associated to the ventral slot. For that, it was used 24 dogs randomly divided into six equal groups. The ventral slot was accomplished in the area of the intervertebral disk C2-C3 and chemonucleolysis in the other cervical disks. Each group of four animals was submitted to euthanasia with an anesthetic overdose 24 hours, eight, 30, 60, 90 and 120 days after the enzyme injection and sagittal sections of the treated disks, associated to adjacent cartilaginous endplates and bony structures were obtained for histological analysis. The dogs were also monitored clinically and radiographically for up to 120 days, according to the groups. In this study, all dogs tolerated the surgical procedure, without detectable postoperative pain, neurological deficit or alteration of the conscience state. In the radiographic evaluation, it was observed consistent disk space narrowing 24 hours after the procedure and total absence of space from the eighth to the 90th day after chemonucleolysis in the area of all treated disks. However, at 120 days of postoperative there was an increase in disk height, corresponding, on average, to 59.13% of the preinjection value. Also, on the 30th day of postoperative, it was noted absorption of the vertebral bodies adjacent to the treated disks that progressed to healing, with evidences of vertebral fusion 120 days after the treatment. In the histological evaluation, it was observed 24 hours after disk injection nuclear digestion, characterized by cavitations and decrease of safranin-O staining intensity, indicating loss of proteoglycans. At eight days, the nuclear content was still vacuolated but more fibrillar. At 30 days, it was noted lesions and hemorrhage in the cartilaginous endplates. An irregularly defined mass in the nuclear space was observed on days 60th and 90th, but it seemed fibrocartilaginous tissue on day 120th. It was also observed microfractures and bone necrosis on day 90th, which were healed by day 120th. Chemonucleolysis with chymopapain associated to the ventral slot in the cervical column of dogs determines lysis of intervertebral disks, cervical instability and lesions of cartilaginous and bone adjacent structures that tend to repair with fibrocartilaginous tissue along the time. / Foram avaliados os aspectos clínico-cirúrgicos, radiográficos e histológicos de discos intervertebrais cervicais após quimionucleólise com quimiopapaína associada à fenda ventral. Foram utilizados 24 cães separados, aleatoriamente, em seis grupos iguais e de acordo com o tempo de observação pós-operatório. A fenda ventral foi realizada na região do disco intervertebral C2-C3 e as quimionucleólises nos demais discos cervicais. Cada grupo de quatro animais foi eutanasiado por sobredose anestésica 24 horas, oito, 30, 60, 90 e 120 dias após aplicação da enzima e foram obtidos cortes sagitais dos discos intervertebrais tratados, associados a estruturas cartilaginosas e ósseas adjacentes, para análise histológica. Os cães foram também avaliados, de acordo com o grupo, clinica e radiograficamente por até 120 dias. Todos os cães toleraram bem o procedimento cirúrgico, não apresentando déficit neurológico, alteração do estado de consciência e dor aparente na região cervical. Na avaliação radiográfica, com 24 horas, observou-se marcada redução da espessura dos espaços intervertebrais. Do oitavo ao 90º dia, foi verificada ausência total de espaço intervertebral na região de todos os discos tratados. Aos 120 dias, entretanto, as espessuras dos espaços intervertebrais correspondiam, em média, a 59,13% da espessura anterior ao procedimento. Ainda, radiograficamente, verificou-se aos 30 dias, absorção das porções dos corpos vertebrais adjacentes aos discos tratados, que progrediu para reparação, inclusive com evidências de fusão vertebral aos 120 dias. Na avaliação histológica, 24 horas após a quimionucleólise, foi observada digestão nuclear caracterizada por cavitações e redução da intensidade de coloração pela safranina-O, indicando perda de proteoglicanos. Aos oito dias, o conteúdo nuclear apresentou-se ainda vacuolizado, contudo mais fibrilar. Aos 30 dias, foram observadas lesões e áreas de hemorragia nas placas terminais cartilaginosas. A partir do 60º dia, notou-se a presença de material amorfo no espaço nuclear, que, aos 120 dias, tinha aparência de tecido fibrocartilaginoso. Aos 90 dias, verificou-se presença de microfraturas e osteonecrose, que estavam reparadas aos 120 dias. A quimionucleólise com quimiopapaína concomitante à fenda ventral na coluna cervical de cães determinou a lise dos discos intervertebrais, instabilidade cervical e lesões nas estruturas cartilaginosas e ósseas adjacentes, que tendem à reparação por tecido fibrocartilaginoso ao longo do tempo. Os trabalhos apresentados como parte integrante desta tese estão seguindo as normas de publicação do Arquivo Brasileiro de Medicina Veterinária e Zootecnia da Universidade Federal de Minas Gerais, indexada ao ISI, AGRIS, BIOSIS, CAB, CAS, MEDLARS e LILACS. ISSN 01020935.