Thesis (Ph. D.)--University of Wisconsin--Madison, 1981. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 125-147).

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Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1978. / Also available via the Internet.

Typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1974. / Bibliography: leaves 131-141. / xiii, 141 leaves ill

No description available.

Two experiments were conducted using newborn colostrum-deprived calves to establish the distribution of uptake of ¹²⁵I- globulin in smail intestine and to investigate effects of added microorganisms on ¹²⁵I-gamma globulin uptake. Ten calves less than 12.5 h of age (X̅ = 7 h) were anesthetized and intestines exteriorized through an abdominal incision. Intestine was ligated into 10 cm segments at 70 cm intervals beginning at the ileocecal junction, injected with ¹²⁵I-gamma globulin in an electrolyte solution and incubated for 1.5 h. One additional segment was formed adjacent to segments 1, 5 and 10 to assess effects of .5 h exposure to ¹²⁵I-gamma globulin on uptake by epithelium. After prescribed gamma globulin exposure, segments were excised, volume of lumen contents, segment weight and tissue activity were determined. Age, birth weight and intestine length were recorded. Location of each segment (PSEG) was expressed as percentage of distance from cecum to abomasum. Uptake was expressed as milligrams gamma globulin internalized per gram of segment tissue. Distribution of gamma globulin uptake after 1.5 h exposure was a cubic function of PSEG. Uptake was greatest In a region 15% of cecumabomasum distance, declining progressively towards the abomasum. After .5 4 exposure, regression of uptake on PSEG was a quadratic function with greatest uptake at 30% of cecum-abomasum distance. Uptake after 1.5 h exposure was greater than after .5 h. In experiment II, 10 calves less than 14 h of age (X̅ = 8.6 h) were anesthetized and intestines surgically exteriorized. Intestine was ligated into segments 10 cm in length at three cm intervals beginning 1.8 m above the ileocecal junction. Seven treatments were assigned in random order to segments in three successive sections of small intestine. Three treatments compared uptake in segments receiving one ml of either live intestine origin bacteria culture, sterile microbiological broth or autoclaved bacteria culture with four h incubation followed by 1.5 h exposure to ¹²⁵I-gamma globulin. Two treatments measured anaerobic microbial growth after four h incubation with one ml of either sterile broth or live bacteria culture. Residual ¹²⁵I-gamma giobulin was measured in segments receiving one ml of sterile broth or live bacteria culture with 5.5 h incubation followed by 15 second exposure to ¹²⁵I-gamma globulin. Measurements were as described for the first 10 calves. Serum corticosteroids, total protein and protein components were measured at O h and 5.5 h later. Uptake was lowest in segments receiving live bacteria as compared to segments receiving sterile inocula. Number of bacteria per gram of segment tissue was negatively correlated with uptake. Low serum corticosteroids were associated with low gamma globulin uptake. Body weight and age were not related to uptake in either experiment.in a decisive manner. / Ph. D.

Introdução: recentemente, foi descrita a ação do abatacepte (ABA) na redução nos níveis de imunoglobulinas (Ig) plasmáticas em pacientes com artrite reumatoide (AR). No entanto, a possível associação destes resultados com infecções não foi avaliada até o presente momento. Objetivos: comparar os níveis totais de Igs, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) em pacientes com AR em uso de ABA vs. agentes anti-TNF semestralmente, durante 24 meses de uso, e correlacioná-los com a presença de infecções. Método: dezoito pacientes consecutivos com AR tratados abatacepte (ABA-AR) foram comparados com 18 pacientes com AR tratados com anti-TNF (aTNF-AR). Dados clínicos, laboratoriais e dosagens de imunoglobulinas total, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) foram obtidos a cada seis meses até o tempo total de 24 meses. Foi feito screening sistemático para presença de infecções. Os critérios de exclusão foram: uso prévio de abatacepte/rituximabe e hipogamablobulinemia basal (< 0,7 g/dL). Resultados: no baseline, as medianas da idade (55 vs. 53 anos, P = 0,92), porcentagem de gênero feminino (78 vs. 78%, P = 1,0), comorbidades (28 vs. 28%, P = 1,0), DAS-28 (5,73 vs. 5,67, P = 0,93), HAQ (1,5 vs. 1,13, P = 0,1), VHS (21,5 vs. 22 mm/1ahora, P = 0,49), PCR (15,5 vs. 12 mg/dL, P = 0,43) e contagem de linfócitos (2.200 vs. 1.800/mm3, P = 0,18) foram semelhantes entre os grupos ABA-AR e aTNF-AR, assim como as medianas da gamaglobulina total (1,4 vs. 1,35 g/dL, P = 0,74), IgG (1.168 vs. 1.079 mg/dL, P = 0,46), IgM (107 vs. 113mg/dL, P = 0,38), IgA (333 vs. 322 mg/dL, P = 0,71), kappa (342 vs. 249 mg/dL, P = 0,39) e lambda (170 vs. 150 mg/dL, P = 0,20). No grupo ABA-AR, após seis meses de uso, houve uma queda dos níveis séricos de gamaglobulina total (1,4 vs. 1,05 g/dL, P < 0,001), IgG (1.168 vs. 997 mg/dL, P < 0,001), IgA (333 vs. 278 mg/dL, P < 0,001), kappa (342 vs. 257 mg/dL, P < 0,001) e lambda (170 vs. 144 mg/dL, P < 0,001). Esses níveis permaneceram estáveis dos seis meses até os 24 meses de tratamento (P > 0,05). Em contraste, no grupo aTNF-AR, não houve alteração nos níveis séricos da gamaglobulina total, suas frações e cadeias leves (P > 0,05) em nenhum momento. A variação negativa da gamaglobulina total, IgG, IgM, IgA, kappa e lambda no grupo ABA-AR foi diferente do grupo aTNF-AR (P < 0,05) em todas as avaliações. No entanto, a frequência de infecções foi semelhante entre os grupos (77,8 vs. 88,9%, P = 0,66) e não se associou às variações da gamaglobulina total, de suas frações ou das cadeias leves em nenhum dos dois grupos. Não houve infecções graves durante o período do estudo. Conclusão: o presente estudo demonstra que o abatacepte, mas não os aTNFs, induz uma queda nos níveis de imunoglobulina total, suas frações e cadeias leves nos primeiros seis meses de uso, com estabilidade nos níveis até 24 meses. No entanto, essa queda não está relacionada ao aumento da frequência de infecções nesse grupo de pacientes / Objective: to evaluate the influence of abatacept on gamma-globulin levels in comparison to anti-TNF treatment and correlate these effects with infections frequency in rheumatoid arthritis (RA) patients. Methods: eighteen consecutive RA patients undergoing abatacept (ABA-RA) were compared to 18 patients treated with anti-TNF (aTNF-RA) agents with similar ages. Clinical and laboratory data, total, specific (IgG, IgM, IgA) gamma-globulin and free light chains (FLC) levels were assessed before and every six months during biologic treatment, up to 24 months. Systematic clinical screening protocol for infection was performed. Exclusion criteria were previous abatacept/rituximab treatments and low gamma-globulin level ( < 0.7 g/dL). Results: at baseline, median age (55 vs. 53 years, P = 0.92), female gender (78 vs. 78%, P = 1.0), co morbities (28 vs. 28%, P = 1), DAS-28 (5.73 vs. 5.67, P = 0.93), HAQ (1.5 vs. 1.13, P = 0.1), ESR (21.5 vs. 22mm/1sth, P = 0.49), CRP (15.5 vs. 12mg/dL, P = 0.43) and lymphocyte count (2,200 vs. 1,800/mm3, P = 0.18) were comparable in ABA-RA and aTNF-RA. Medians of gamma-globulin (1.4 vs. 1.35g/dL, P = 0.74), IgG (1,168 vs. 1,079mg/dL, P = 0.46), IgM (107 vs. 113mg/dL, P = 0.38), IgA (333 vs. 322mg/dL, P = 0.71), kappa (342 vs. 249mg/dL, P = 0.39), lambda (170 vs. 150mg/dL, P = 0.20) were also alike. In ABA-RA, total gamma-globulin (1.4 vs. 1.05 g/dL, P < 0.001), IgG (1,168 vs. 997 mg/dL, P < 0.001), IgA (333 vs. 278 mg/dL, P < 0.001), kappa (341.5 vs. 257 mg/dL, P < 0.001), lambda (169.5 vs. 144.3 mg/dL, P < 0.001) levels decreased after six months in comparison to baseline values and persisted stable up to 24 months (P > 0.05). In contrast, in aTNF-RA no decrease in total, specific gamma-globulin levels or FLC was seen (P > 0.05). The negative variation of gamma-globulin, IgG, IgM, IgA, kappa and lambda levels in ABA-RA was different from aTNF-RA (P < 0.05) at all evaluations. However, the infection rates (77.8 vs. 88.9%, P = 0.66) were similar and not associated to variations in total or specific gamma-globulin levels in any group. No severe infection was observed. Conclusion: these comparative data demonstrate that ABA, but not the aTNF, induces a non-progressive and mild, but significant reduction in gamma-globulin levels. We further demonstrated that this alteration is not clinically relevant since it is not associated with increased infection rate

Introdução: recentemente, foi descrita a ação do abatacepte (ABA) na redução nos níveis de imunoglobulinas (Ig) plasmáticas em pacientes com artrite reumatoide (AR). No entanto, a possível associação destes resultados com infecções não foi avaliada até o presente momento. Objetivos: comparar os níveis totais de Igs, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) em pacientes com AR em uso de ABA vs. agentes anti-TNF semestralmente, durante 24 meses de uso, e correlacioná-los com a presença de infecções. Método: dezoito pacientes consecutivos com AR tratados abatacepte (ABA-AR) foram comparados com 18 pacientes com AR tratados com anti-TNF (aTNF-AR). Dados clínicos, laboratoriais e dosagens de imunoglobulinas total, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) foram obtidos a cada seis meses até o tempo total de 24 meses. Foi feito screening sistemático para presença de infecções. Os critérios de exclusão foram: uso prévio de abatacepte/rituximabe e hipogamablobulinemia basal (< 0,7 g/dL). Resultados: no baseline, as medianas da idade (55 vs. 53 anos, P = 0,92), porcentagem de gênero feminino (78 vs. 78%, P = 1,0), comorbidades (28 vs. 28%, P = 1,0), DAS-28 (5,73 vs. 5,67, P = 0,93), HAQ (1,5 vs. 1,13, P = 0,1), VHS (21,5 vs. 22 mm/1ahora, P = 0,49), PCR (15,5 vs. 12 mg/dL, P = 0,43) e contagem de linfócitos (2.200 vs. 1.800/mm3, P = 0,18) foram semelhantes entre os grupos ABA-AR e aTNF-AR, assim como as medianas da gamaglobulina total (1,4 vs. 1,35 g/dL, P = 0,74), IgG (1.168 vs. 1.079 mg/dL, P = 0,46), IgM (107 vs. 113mg/dL, P = 0,38), IgA (333 vs. 322 mg/dL, P = 0,71), kappa (342 vs. 249 mg/dL, P = 0,39) e lambda (170 vs. 150 mg/dL, P = 0,20). No grupo ABA-AR, após seis meses de uso, houve uma queda dos níveis séricos de gamaglobulina total (1,4 vs. 1,05 g/dL, P < 0,001), IgG (1.168 vs. 997 mg/dL, P < 0,001), IgA (333 vs. 278 mg/dL, P < 0,001), kappa (342 vs. 257 mg/dL, P < 0,001) e lambda (170 vs. 144 mg/dL, P < 0,001). Esses níveis permaneceram estáveis dos seis meses até os 24 meses de tratamento (P > 0,05). Em contraste, no grupo aTNF-AR, não houve alteração nos níveis séricos da gamaglobulina total, suas frações e cadeias leves (P > 0,05) em nenhum momento. A variação negativa da gamaglobulina total, IgG, IgM, IgA, kappa e lambda no grupo ABA-AR foi diferente do grupo aTNF-AR (P < 0,05) em todas as avaliações. No entanto, a frequência de infecções foi semelhante entre os grupos (77,8 vs. 88,9%, P = 0,66) e não se associou às variações da gamaglobulina total, de suas frações ou das cadeias leves em nenhum dos dois grupos. Não houve infecções graves durante o período do estudo. Conclusão: o presente estudo demonstra que o abatacepte, mas não os aTNFs, induz uma queda nos níveis de imunoglobulina total, suas frações e cadeias leves nos primeiros seis meses de uso, com estabilidade nos níveis até 24 meses. No entanto, essa queda não está relacionada ao aumento da frequência de infecções nesse grupo de pacientes / Objective: to evaluate the influence of abatacept on gamma-globulin levels in comparison to anti-TNF treatment and correlate these effects with infections frequency in rheumatoid arthritis (RA) patients. Methods: eighteen consecutive RA patients undergoing abatacept (ABA-RA) were compared to 18 patients treated with anti-TNF (aTNF-RA) agents with similar ages. Clinical and laboratory data, total, specific (IgG, IgM, IgA) gamma-globulin and free light chains (FLC) levels were assessed before and every six months during biologic treatment, up to 24 months. Systematic clinical screening protocol for infection was performed. Exclusion criteria were previous abatacept/rituximab treatments and low gamma-globulin level ( < 0.7 g/dL). Results: at baseline, median age (55 vs. 53 years, P = 0.92), female gender (78 vs. 78%, P = 1.0), co morbities (28 vs. 28%, P = 1), DAS-28 (5.73 vs. 5.67, P = 0.93), HAQ (1.5 vs. 1.13, P = 0.1), ESR (21.5 vs. 22mm/1sth, P = 0.49), CRP (15.5 vs. 12mg/dL, P = 0.43) and lymphocyte count (2,200 vs. 1,800/mm3, P = 0.18) were comparable in ABA-RA and aTNF-RA. Medians of gamma-globulin (1.4 vs. 1.35g/dL, P = 0.74), IgG (1,168 vs. 1,079mg/dL, P = 0.46), IgM (107 vs. 113mg/dL, P = 0.38), IgA (333 vs. 322mg/dL, P = 0.71), kappa (342 vs. 249mg/dL, P = 0.39), lambda (170 vs. 150mg/dL, P = 0.20) were also alike. In ABA-RA, total gamma-globulin (1.4 vs. 1.05 g/dL, P < 0.001), IgG (1,168 vs. 997 mg/dL, P < 0.001), IgA (333 vs. 278 mg/dL, P < 0.001), kappa (341.5 vs. 257 mg/dL, P < 0.001), lambda (169.5 vs. 144.3 mg/dL, P < 0.001) levels decreased after six months in comparison to baseline values and persisted stable up to 24 months (P > 0.05). In contrast, in aTNF-RA no decrease in total, specific gamma-globulin levels or FLC was seen (P > 0.05). The negative variation of gamma-globulin, IgG, IgM, IgA, kappa and lambda levels in ABA-RA was different from aTNF-RA (P < 0.05) at all evaluations. However, the infection rates (77.8 vs. 88.9%, P = 0.66) were similar and not associated to variations in total or specific gamma-globulin levels in any group. No severe infection was observed. Conclusion: these comparative data demonstrate that ABA, but not the aTNF, induces a non-progressive and mild, but significant reduction in gamma-globulin levels. We further demonstrated that this alteration is not clinically relevant since it is not associated with increased infection rate