Samples from 93 of 115 consecutive cadaveric renal transplants were selected to define polymorphisms in both IFN-γ and IL-10. A 12 CA repeat IFN-γ polymorphic allele was found in 73 patients (70 in patients analysed further). This polymorphism was associated with high IFN-γ production in vitro. According to the presence or not of the 12 CA repeat allele patients were separated in high and low producer genotype groups. The incidence of acute rejection was 54.3% in this high IFN-γ genotype group, contrasting with 44.4% in the low IFN-γ. Requirement for ATG therapy was greater in the high IFN-γ group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-γ high producer genotype was more strongly associated with rejection (OR=1.6). In the cyclosporine monotherapy subgroup, 11 out of 14 patients with IFN-γ high genotype (78%) had acute rejection (OR=2.88, p=0.09). Graft survival was similar between the two IFN-γ groups. When the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-γ genotype patients had serum creatinine levels above 200 micromoles/L contrasting with only 14.3% of the low IFN-γ genotype recipients at 5 years after transplantation (p=0.05). In a regression model of creatinine at 1 year the significant variables were the presence of DGF, donor age greater than 50, greater than two rejection episodes, DR mismatch, donor female to male recipient sex, IL-10 high genotype, and IFN-γ high genotype. Conclusion: The 12 CA repeat IFN-γ polymorphic allele is associated with high IFN-γ production. We have shown that this high producer genotype for IFN-γ influences acute rejection in kidney transplantation, particularly in high-risk groups; it is also associated with worse long-term graft function.

No description available.

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Autologous Bone Marrow Transplantation (ABMT) provides a way to rescue the hematopoietic system in patients receiving high dose chemotherapy. Solid tumors like lung and breast cancer are the targets for new therapies that involve high dose chemotherapy with AMBT due to their growth and pathologic characteristics. Reinfusion of bone marrow with metastatic neoplastic cells could also seed viable tumor cells, and thus be a reason for treatment failure, restricting high-dose chemotherapy with bone marrow support to patients whose marrow is morphologically free of tumor cells. The use magnetic beads for physical separation of tumor from normal cells and the use of a toxin delivered by a monoclonal antibody are examined as two purging methods for treatment. The use of magnetic beads conjugated with specific antibodies (SM1, LAM2 and LS1) against tumor antigens to purge 2-3 logs of Small Cell Lung Cancer (SCLC) contamination from bone marrow is demonstrated. Optimal performance calls for short double exposure to anti-tumor cell-antigen monoclonal antibodies, followed by exposure to magnetic beads coated with antibodies specific for the monoclonal anti-SCLC antibodies, maintaining a bead-to-cell ratio of 10:1 to 100:1. Specific toxin delivery to three breast cancer cell lines (ZR-75, BT20 and MCF7) expressing the DF3 antigen was demonstrated by the use of DF3 immunotoxin (DF3-IT). The optimal concentration of the DF3-IT immunotoxin for highest tumor kill was shown to be 1x1Q-9 M, but this caused a loss of bone marrow progenitor cell colonies of about 30%. Both methods are limited chiefly by the level of antigen expression in the target tumor cells. The purging efficiency could be improved by targeting a wider range of antigens or by inducing higher levels of antigen expression. From the clinical perspective, the advantages and need for purging involved bone marrow to bring about substantially improved curative strategies remains a question still unanswered. / 2031-01-01

This thesis explores the making of Thailand’s Civil and Commercial Code in 1925 (‘Code of 1925’), especially the drafting method the draftsmen employed, and ascertains how the use of this method affected Thai lawyers’ understanding of rules and concepts of the Code. The Code of 1925 emerged from a period in which Thailand was under threat from colonisation by Western powers. As a result of a number of unbalanced commercial treaties between the Thai and foreign governments, the jurisdictional sovereignty of the country had been eroded by consular jurisdiction and the principle of extraterritoriality. These ‘unfair treaties’ forced the Thai government to establish a modern legal system as part of its attempts to recover full judicial autonomy. The work of codification of civil and commercial law, which began in 1908 under the direction of French draftsmen, produced the desired result in 1925 only after Phraya Manavarajasevi (Plod na Songkhla) became involved. Plod was instrumental in replacing the French Code civil with the BGB of 1900 as the principal model and introducing the Japanese Civil Code of 1898 (‘Minpō’) and the ‘copying method’ which he referred to as the ‘Japanese method’ to the new Thai-dominated drafting committee. The Japanese Code and the ‘Japanese method’ were chosen owing to Plod’s belief that the Japanese had established their civil code by copying the BGB. This thesis shows that Alan Watson’s theory of legal transplants is well suited for explaining this type of legal development: the draftsmen copied the wording of English translations of provisions of the BGB and the Minpō without much concern about their conceptual foundations. They finished their task within seven months. But Watson’s contention that successful legal borrowing does not require ‘a systematic knowledge of the law’ must be approached with great caution. Plod was misled by a secondary source he consulted into believing that the Minpō was practically a copy of the BGB. In reality, the Japanese Code was influenced by a variety of foreign laws, including German and French law. The drafting committee’s lack of knowledge about the rules and concepts they borrowed and the method they adopted led to difficulties in interpreting the rules and concepts in question. This is illustrated in this thesis by a case study of the legal rules in the Code of 1925 on specific performance. Most of the Thai provisions concerning non-performance and remedies for non-performance were copied from the BGB, but two important rules concerning the rights to performance and damages (Articles 213 and 215) came from the Minpō. These provisions were mainly influenced by French law, but Plod and most likely other Thai draftsmen erroneously believed that they were of German origin. The text of these two articles clearly put specific performance and damages as remedies for non-performance on equal footing. The consequence of this is that Thai academics who maintain that specific performance is the primary remedy for nonperformance have struggled to justify this point of view. Whenever they expound on the principle of the primacy of specific performance in Thai law, Thai writers produce contradictory statements because the wording of Articles 213 and 215 forces them to accept that the creditor in case of non-performance has the right to choose between specific performance and damages. This thesis shows that legal borrowing without a proper use of comparative law and legal history and a systematic knowledge of the law borrowed can lead to undesirable results. Thai lawyers must employ comparative and historical methods when discovering the true character of the Thai rules and concepts. With the help of these methods, they may find common ground in legal concepts and resolve some theoretical problems.

Made available in DSpace on 2014-06-11T19:33:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-28Bitstream added on 2014-06-13T20:44:58Z : No. of bitstreams: 1 ribeiro_llg_dr_araca.pdf: 812751 bytes, checksum: cd179aa3279006a23852da0cdbcc62cd (MD5) / A recessão gengival (RG) consiste na migração da margem gengival (MG) em direção apical à junção cemento-esmalte (JCE), deixando a raiz do dente exposta. O recobrimento da RG com a técnica do enxerto gengival livre (EGL) pode ocorrer imediatamente por meio de “bridging,” ou tardiamente por meio de “creeping attachment” (CA). O objetivo do presente estudo é avaliar a influência da remoção da margem gengival e do posicionamento do enxerto gengival livre sobre o “creeping attachment” em recessões classe II de Miller em pré-molares inferiores. Os pacientes deveriam ter um ou os dois pré-molares inferiores com recessões classe II de Miller de um ou ambos os lados. Eles foram divididos aleatoriamente em um dos grupos de acordo com sua chegada: Grupo 1: Preparo do leito receptor e sutura do EGL apical a um colar de MG mantida ao redor do dente. Grupo 2: Preparo do leito receptor removendo-se toda a MG e posicionando o EGL sem recobrir a porção exposta da raiz. Grupo 3: Preparo do leito receptor semelhante ao do Grupo 2 e posicionamento do EGL no nível da JCE. Foram feitas medições pré e pós-operatórias aos 30, 90, 180 e 360 dias da altura da RG (HR), largura da RG (LR), quantidade de gengiva queratinizada (GQ), profundidade de sondagem (PS), gengiva inserida (GI) e nível de inserção clínica (NIC). O recobrimento inicial (RI) e o CA foram calculados com as medidas obtidas. Os dados foram submetidos à análise estatística. Aos 360 dias pósoperatórios, a porcentagem de recobrimento dos Grupos 1, 2 e 3 foi de 4,12%; 39,58% e 30,99% respectivamente. Não houve diferença estatística de RI entre os grupos. A quantidade de CA, aos 90, 180 e 360 dias pós-operatórios, não foi estatisticamente significante entre os grupos. Os Grupos 2 e 3 tiveram redução significativa no nível de inserção clínica aos 360 dias pós-operatórios. / Gingival recession is the result of the apical migration of the free gingival margin (FGM), resulting in root exposure. The direct root coverage (DRC) obtained by free gingival graft (FGG) technique is the result of bridging, while root coverage obtained later is the result of creeping attachment (CA). The purpose of this study was to assess the influence of free gingival margin excision and free gingival graft adaptation on creeping attachment on lower premolars. 48 patients with or without bilateral Miller class II defects on one or both lower premolars were selected and randomly assigned to one of the following groups: Group 1 - FGG was placed apically to the collar of residual gingiva left in place at the moment of preparing the recipient bed. Group 2 – FGG was placed at the coronal border of the recipient bed after excision of FGM without any attempt to cover the denuded root. Group 3 – a direct coverage of the recession was attempted by placing the FGG with its coronal border at the level of cemento-enamel junction (CEJ). Height of recession (HR), width of recession (WR), height of keratinized tissue (HKT) were assessed at baseline and at 30, 90, 180 and 360 days postoperatively. Probing depth (PD), attached gingiva (AG) and clinical attachment level (CAL) were assessed at 360 days postoperatively. DRC and CA were calculated with the obtained measurements. The mean percentage of root coverage in the Groups 1, 2 and 3 were 4,12%; 39,58% and 30,99% respectively at 360 days post-op. All groups exhibited statistically similar DRC and CA. Groups 2 and 3 presented significantly gain in attachment level.

Made available in DSpace on 2014-06-11T19:27:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-24Bitstream added on 2014-06-13T19:36:17Z : No. of bitstreams: 1 santos_dc_me_botfm.pdf: 374235 bytes, checksum: 200e9fdd6e375a5ea8f815b5dd000cfc (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Trata-se de estudo retrospectivo, que visou estudar o papel do C4d, da capilarite e dos macrófagos na rejeição aguda renal. Foram estudados 76 casos de rejeição aguda entre 1991 e 2009. Primariamente, foi realizada análise histológica e reclassificação de todos os casos nos tipos de rejeição aguda (RA) I, II e III, segundo os critérios de Banff 97 para rejeição aguda do tipo celular (mediada por células T). A capilarite foi classificada pelos escores de Banff e por um segundo método de contagem proposto pelo estudo (ptc média), analisado através da contagem de todas as células inflamatórias intracapilares em 10 campos de aumento 400X. Foi realizado estudo imunoistoquímico para pesquisa de C4d e macrófagos em 69 e 47 casos, respectivamente. Identificamos 46 biópsias como RA tipo I, 21 como tipo II e, 9, tipo III. De 69 biópsias, 20 foram C4d positivas (14 padrão focal e 6, difuso). C4d se associou com glomerulite, capilarite (ptc média) e macrófagos. A capilarite estudada através do escore de Banff apresentou associação apenas com os tipos de rejeição (P=0,04). Entretanto, a capilarite (ptc média) além da associação com o C4d, teve correlação com macrófagos (P=0,01) e com a creatinina no momento da biópsia (CrIcreatinina inicial-P<0,05). Houve significância estatística entre macrófagos e tipos de rejeição, com maior número de macrófagos no grupo de RA tipo II+III (P=0,03) e no escore v3 (P=0,04). A perda do enxerto se associou com C4d positivo, glomerulite e RA tipo III. Em conclusão, o estudo demonstrou associação entre C4d positivo e lesões inflamatórias identificadas nos capilares, tanto peritubulares como glomerulares, com associação também para a infiltração por macrófagos. O conjunto de resultados sugere a possibilidade de componente humoral nos casos estudados / We investigate the role of C4d deposition in peritubular capillaries, peritubular capillaritis and macrophage infiltration in acute renal rejection and, we evaluate their associations with morphological and clinical data. The study included 76 patients between 1991 and 2009. Histologic analysis of acute rejection I, II and III types was done by Banff 97 classification. Capillaritis was classified by the ptc Banff scores and by counting cells within peritubular capillaries in 10 high power fields 400X (ptc mean cells). C4d and macrophages were analyzed by immunohistochemistry, in 69 and 47 cases, respectivelly. Forty-six biopsies as type I, 21 type II and 9 type III were found. Twenty cases were positive C4d (14 focally and 6 diffuse). There were positive association between C4d staining and glomerulitis, peritubular capillaritis (ptc mean) and macrophage infiltration. Capillaritis using ptc Banff scores showed only statistical significant difference to type of rejection (P=0.04). Capillaritis analyzed by counting cells (ptc mean), beyond association with C4d, correlated to macrophage infiltration (P=0,01) and initial serum creatinine (P<0,05). Macrophage infiltration was significantly different between type I and II+III rejection (P=0,03) and showed increased arteritis score (v3) (P=0,04). Macrophage had also correlation with initial serum creatinine (P=0,004). There was significant graft loss in type III rejection, positive C4d and positive glomerulitis cases The study demonstrated association between positive C4d cases and inflammatory lesions of glomerular and peritubular capillaries; there were more frequency of glomerulitis, peritubular capillaritis (ptc mean) and macrophage infiltrate in the positive C4d cases. These results can suggest a possible humoral component in the studied cases

Made available in DSpace on 2014-10-09T12:33:39Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:04:03Z (GMT). No. of bitstreams: 0 / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP

Orientador: Rosa Marlene Viero / Banca: Daisa Silva Ribeiro David / Banca: Gyl Eanes Barros Silva / Resumo: Trata-se de estudo retrospectivo, que visou estudar o papel do C4d, da capilarite e dos macrófagos na rejeição aguda renal. Foram estudados 76 casos de rejeição aguda entre 1991 e 2009. Primariamente, foi realizada análise histológica e reclassificação de todos os casos nos tipos de rejeição aguda (RA) I, II e III, segundo os critérios de Banff 97 para rejeição aguda do tipo celular (mediada por células T). A capilarite foi classificada pelos escores de Banff e por um segundo método de contagem proposto pelo estudo (ptc média), analisado através da contagem de todas as células inflamatórias intracapilares em 10 campos de aumento 400X. Foi realizado estudo imunoistoquímico para pesquisa de C4d e macrófagos em 69 e 47 casos, respectivamente. Identificamos 46 biópsias como RA tipo I, 21 como tipo II e, 9, tipo III. De 69 biópsias, 20 foram C4d positivas (14 padrão focal e 6, difuso). C4d se associou com glomerulite, capilarite (ptc média) e macrófagos. A capilarite estudada através do escore de Banff apresentou associação apenas com os tipos de rejeição (P=0,04). Entretanto, a capilarite (ptc média) além da associação com o C4d, teve correlação com macrófagos (P=0,01) e com a creatinina no momento da biópsia (CrIcreatinina inicial-P<0,05). Houve significância estatística entre macrófagos e tipos de rejeição, com maior número de macrófagos no grupo de RA tipo II+III (P=0,03) e no escore v3 (P=0,04). A perda do enxerto se associou com C4d positivo, glomerulite e RA tipo III. Em conclusão, o estudo demonstrou associação entre C4d positivo e lesões inflamatórias identificadas nos capilares, tanto peritubulares como glomerulares, com associação também para a infiltração por macrófagos. O conjunto de resultados sugere a possibilidade de componente humoral nos casos estudados / Abstract: We investigate the role of C4d deposition in peritubular capillaries, peritubular capillaritis and macrophage infiltration in acute renal rejection and, we evaluate their associations with morphological and clinical data. The study included 76 patients between 1991 and 2009. Histologic analysis of acute rejection I, II and III types was done by Banff 97 classification. Capillaritis was classified by the ptc Banff scores and by counting cells within peritubular capillaries in 10 high power fields 400X (ptc mean cells). C4d and macrophages were analyzed by immunohistochemistry, in 69 and 47 cases, respectivelly. Forty-six biopsies as type I, 21 type II and 9 type III were found. Twenty cases were positive C4d (14 focally and 6 diffuse). There were positive association between C4d staining and glomerulitis, peritubular capillaritis (ptc mean) and macrophage infiltration. Capillaritis using ptc Banff scores showed only statistical significant difference to type of rejection (P=0.04). Capillaritis analyzed by counting cells (ptc mean), beyond association with C4d, correlated to macrophage infiltration (P=0,01) and initial serum creatinine (P<0,05). Macrophage infiltration was significantly different between type I and II+III rejection (P=0,03) and showed increased arteritis score (v3) (P=0,04). Macrophage had also correlation with initial serum creatinine (P=0,004). There was significant graft loss in type III rejection, positive C4d and positive glomerulitis cases The study demonstrated association between positive C4d cases and inflammatory lesions of glomerular and peritubular capillaries; there were more frequency of glomerulitis, peritubular capillaritis (ptc mean) and macrophage infiltrate in the positive C4d cases. These results can suggest a possible humoral component in the studied cases / Mestre

Orientador: Álvaro Francisco Bosco / Banca: Maria Lúcia Rubo de Rezende / Banca: Mário Taba Júnior / Banca: Maria José Hitomi Nagata / Banca: Valdir Gouveia Garcia / Resumo: A recessão gengival (RG) consiste na migração da margem gengival (MG) em direção apical à junção cemento-esmalte (JCE), deixando a raiz do dente exposta. O recobrimento da RG com a técnica do enxerto gengival livre (EGL) pode ocorrer imediatamente por meio de "bridging," ou tardiamente por meio de "creeping attachment" (CA). O objetivo do presente estudo é avaliar a influência da remoção da margem gengival e do posicionamento do enxerto gengival livre sobre o "creeping attachment" em recessões classe II de Miller em pré-molares inferiores. Os pacientes deveriam ter um ou os dois pré-molares inferiores com recessões classe II de Miller de um ou ambos os lados. Eles foram divididos aleatoriamente em um dos grupos de acordo com sua chegada: Grupo 1: Preparo do leito receptor e sutura do EGL apical a um colar de MG mantida ao redor do dente. Grupo 2: Preparo do leito receptor removendo-se toda a MG e posicionando o EGL sem recobrir a porção exposta da raiz. Grupo 3: Preparo do leito receptor semelhante ao do Grupo 2 e posicionamento do EGL no nível da JCE. Foram feitas medições pré e pós-operatórias aos 30, 90, 180 e 360 dias da altura da RG (HR), largura da RG (LR), quantidade de gengiva queratinizada (GQ), profundidade de sondagem (PS), gengiva inserida (GI) e nível de inserção clínica (NIC). O recobrimento inicial (RI) e o CA foram calculados com as medidas obtidas. Os dados foram submetidos à análise estatística. Aos 360 dias pósoperatórios, a porcentagem de recobrimento dos Grupos 1, 2 e 3 foi de 4,12%; 39,58% e 30,99% respectivamente. Não houve diferença estatística de RI entre os grupos. A quantidade de CA, aos 90, 180 e 360 dias pós-operatórios, não foi estatisticamente significante entre os grupos. Os Grupos 2 e 3 tiveram redução significativa no nível de inserção clínica aos 360 dias pós-operatórios. / Abstract: Gingival recession is the result of the apical migration of the free gingival margin (FGM), resulting in root exposure. The direct root coverage (DRC) obtained by free gingival graft (FGG) technique is the result of bridging, while root coverage obtained later is the result of creeping attachment (CA). The purpose of this study was to assess the influence of free gingival margin excision and free gingival graft adaptation on creeping attachment on lower premolars. 48 patients with or without bilateral Miller class II defects on one or both lower premolars were selected and randomly assigned to one of the following groups: Group 1 - FGG was placed apically to the collar of residual gingiva left in place at the moment of preparing the recipient bed. Group 2 - FGG was placed at the coronal border of the recipient bed after excision of FGM without any attempt to cover the denuded root. Group 3 - a direct coverage of the recession was attempted by placing the FGG with its coronal border at the level of cemento-enamel junction (CEJ). Height of recession (HR), width of recession (WR), height of keratinized tissue (HKT) were assessed at baseline and at 30, 90, 180 and 360 days postoperatively. Probing depth (PD), attached gingiva (AG) and clinical attachment level (CAL) were assessed at 360 days postoperatively. DRC and CA were calculated with the obtained measurements. The mean percentage of root coverage in the Groups 1, 2 and 3 were 4,12%; 39,58% and 30,99% respectively at 360 days post-op. All groups exhibited statistically similar DRC and CA. Groups 2 and 3 presented significantly gain in attachment level. / Doutor

Made available in DSpace on 2014-10-09T12:33:39Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:04:03Z (GMT). No. of bitstreams: 0 / Extensas lesões na pele expõem o organismo a uma série de agentes agressores, dificultando a reparação espontânea da pele e muitas vezes levando o paciente a óbito. Nesse caso, se não houver áreas doadoras de autoenxertos, pode se utilizar aloenxertos. Neste tipo de enxerto, os tecidos são processados em Bancos de Tecidos, onde se pode empregar a radiação ionizante como método de esterilização. De acordo com estudos in vitro, a radiação gama, em doses acima de 25 kGy, provoca desestruturação das fibrilas de colágeno I da derme conservada em glicerol na concentração de 85%, reduzindo significativamente a resistência à tração dos tecidos irradiados. Observações clínicas sugerem, ainda, integração mais rápida da derme humana, conservada em glicerol e submetida à radiação ionizante, com os tecidos do receptor, quando comparada à derme somente conservada em glicerol. Para verificar se essas alterações relatadas in vitro, comprometeriam o emprego in vivo, de amostras de pele humana, submetidas à radiação gama, foram realizados transplantes de peles humanas, irradiadas ou não, em camundongos Nude. A pele dos camundongos foi submetida à análise macroscópica, imagens de tomografia de coerência óptica, histologia e ensaios biomecânicos. Foi possível concluir que os enxertos irradiados a 25 kGy promoveram uma contração inicial maior, mas essa alteração não interferiu na dimensão da área final de reparação, ainda, os animais que receberam esses enxertos apresentaram mais rápido fechamento da ferida em comparação com os demais, além disso o emprego de enxertos irradiados (25 e 50 kGy) promoveu a formação de um processo de reparação mais organizado e sem efeitos significantes nas propriedades biomecânicas. / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP