RESUMO
The ability of interferon gamma (IFN-gamma) to inhibit the proliferation of type 2 T helper cells (TH2), but not that of type 1 (TH1) cells, suggests that helper cell subsets might differ in their activation of the IFN-gamma signaling pathway. The IFN-gamma-inducible signal transducing factor (STF-IFN gamma) was activated in murine TH2 but not in TH1 cell clones, because in the latter the second chain of the IFN-gamma receptor (accessory factor 1 or IFN-gamma R beta) was absent. Thus, TH1 cells use receptor modification to prevent the activation of STF-IFN gamma and achieve an IFN-gamma-resistant state.
Assuntos
Interferon gama/fisiologia , Proteínas Proto-Oncogênicas , Receptores de Interferon/fisiologia , Transdução de Sinais , Células Th1/imunologia , Células Th2/imunologia , Animais , Sequência de Bases , Células Clonais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Regulação da Expressão Gênica , Fator Regulador 1 de Interferon , Interferon gama/farmacologia , Interleucina-4/farmacologia , Janus Quinase 1 , Janus Quinase 2 , Camundongos , Dados de Sequência Molecular , Fosfoproteínas/genética , Proteínas Tirosina Quinases/metabolismo , Fator de Transcrição STAT1 , Células Th1/metabolismo , Células Th2/metabolismo , Transativadores/metabolismo , Receptor de Interferon gamaRESUMO
OBJECTIVE: To assess the influence of surgical technique (telescoped versus end-to-end anastomosis) on the incidence of bronchial anastomotic complications in patients who underwent single lung transplantation for pulmonary emphysema. METHODS: Seventy-six adult recipients of single lung transplants for pulmonary emphysema were evaluated for the presence of 3 types of major bronchial anastomotic complications: ischemia, dehiscence, and severe stenosis. Surgical technique, clinical course, and mortality were reviewed retrospectively. RESULTS: The 3 major complications were observed in 11 (34%; ischemia), 8 (25%; dehiscence), and 11 (34%; severe stenosis) of 32 telescoped bronchial anastomoses. In contrast, ischemia, dehiscence, and severe stenosis occurred in only 4 (9%), 1 (2%), and 2 (5%) of 44 end-to-end anastomoses (P =.0087, P =.0034, and P =.0012, respectively). The relative risk of ischemia, dehiscence, and severe stenosis in telescoped anastomoses was 2.1, 2.5, and 2.5, respectively, compared with end-to-end anastomoses. Five (13%) telescoped anastomoses required stent placement as compared with only 2 (5%) end-to-end anastomoses (P =.1244). Early postoperative pneumonia was more common in the telescoped anastomosis group (56%) than in the end-to-end group (32%; P =.0380). There was a trend toward shorter survival in the telescoped anastomosis group (mean survival 1045 +/- 145 days) as compared with the end-to-end group (mean survival 1289 +/- 156 days), but these differences did not achieve statistical significance (P =.2410). CONCLUSIONS: In patients who underwent single lung transplantation for pulmonary emphysema, telescoped anastomoses were associated with a higher incidence of bronchial anastomotic complications than end-to-end anastomoses.
Assuntos
Brônquios/cirurgia , Transplante de Pulmão , Enfisema Pulmonar/cirurgia , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/mortalidade , Brônquios/irrigação sanguínea , Brônquios/patologia , Broncoscopia , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Feminino , Humanos , Incidência , Isquemia/epidemiologia , Isquemia/etiologia , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Cardiopulmonary bypass can be associated with vasodilatory hypotension requiring pressor support. We have previously found arginine vasopressin to be a remarkably effective pressor in a variety of vasodilatory shock states. We investigated the incidence and clinical predictors of vasodilatory shock in a general population of cardiac surgical patients and the effects of low-dose arginine vasopressin as treatment of this syndrome in patients with heart failure. METHODS: Patients undergoing cardiopulmonary bypass (n = 145) were studied prospectively. Preoperative ejection fraction, medications, and perioperative hemodynamics were recorded, and postbypass serum arginine vasopressin levels were measured. Vasodilatory shock was defined as a mean arterial pressure lower than 70 mm Hg, a cardiac index greater than 2.5 L/min/m2, and norepinephrine dependence. Predictors of vasodilatory shock were investigated by logistic regression analysis. The hemodynamic responses of patients who received arginine vasopressin infusions for vasodilatory shock after cardiopulmonary bypass for left ventricular assist device placement or heart transplantation were analyzed retrospectively. RESULTS: Eleven of 145 general cardiac surgery patients (8%) met criteria for postbypass vasodilatory shock. By multivariate analysis, an ejection fraction lower than 0.35 and angiotensin-converting enzyme inhibitor use were independent predictors of postbypass vasodilatory shock (relative risks of 9.1 and 11.9, respectively). Vasodilatory shock was associated with inappropriately low serum arginine vasopressin concentrations (12.0 +/- 6.6 pg/mL). Retrospective analysis found 40 patients with postbypass vasodilatory shock who received low-dose arginine vasopressin infusions, resulting in increased mean arterial pressure and decreased norepinephrine requirements. CONCLUSIONS: Low ejection fraction and angiotensin-converting enzyme inhibitor use are risk factors for postbypass vasodilatory shock, and this syndrome is associated with vasopressin deficiency. In patients exhibiting this syndrome after high-risk cardiac operations, replacement of arginine vasopressin increases blood pressure and reduces catecholamine pressor requirements.
Assuntos
Arginina Vasopressina/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Choque/tratamento farmacológico , Vasoconstritores/uso terapêutico , Vasodilatação/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/sangue , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/sangue , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Hipotensão/sangue , Hipotensão/tratamento farmacológico , Hipotensão/etiologia , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Choque/sangue , Choque/etiologia , Vasoconstritores/administração & dosagemRESUMO
Efforts aimed at limiting the pool of cardiac retransplantation candidates have focused increasingly on attempts to preserve cardiac allograft function. The present report reviews the course of a patient who underwent mitral valve replacement and tricuspid annuloplasty for bivalvular incompetence after cardiac transplantation and examines the limited reported world experience with valve replacement after transplantation. The limited yet successful experiences with these and other operations in cardiac allograft recipients suggest that worsening donor organ shortages will likely lead to increased clinical experience with conventional operations in the transplanted heart.
Assuntos
Transplante de Coração , Próteses Valvulares Cardíacas , Valva Mitral/cirurgia , Complicações Pós-Operatórias/cirurgia , Valva Tricúspide/cirurgia , Cardiomiopatia Dilatada/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/cirurgiaRESUMO
PURPOSE: To compare complication rates of telescoped versus end-to-end bronchial anastomoses in single and bilateral lung transplantation. METHODS: One hundred and thirty adult lung transplant recipients were evaluated during a seven-year period for the presence of three types of major bronchial anastomotic complications (ischemia, dehiscence, and severe stenosis). Surgical technique, clinical course, and mortality in all patients were reviewed retrospectively. RESULTS: The three major complications, ischemia, dehiscence, and severe stenosis, were observed in 13 (32%), 10 (24%), and 13 (32%), respectively, of 41 telescoped bronchial anastomoses. In contrast, ischemia, dehiscence, and severe stenosis, occurred in 25 (19%), 14 (10%), and 11 (8%) of 135 end-to end anastomoses. These differences were statistically significant for the occurrence of dehiscence and severe stenosis (p=0.0350 and 0.0004, respectively), and not statistically significant for ischemia (p=0.0846). Five (12%) telescoped anastomoses required stent placement as compared with six (4%) end-to end anastomoses (p=0.1313). Early postoperative pneumonia was more common in the telescoped anastomosis group (57%) as compared to the end-to-end group (35%; p=0.0271). There was a trend to shorter survival in the telescoped anastomosis group (mean survival 1172+/-149 d) as compared to the end-to-end group (mean survival 1542+/-126 d), but these differences did not achieve statistical significance (p=0.2400). CONCLUSION: In single and bilateral lung transplants, telescoped anastomoses are associated with a higher incidence of bronchial anastomotic complications and postoperative pneumonia than end-to-end anastomoses.
Assuntos
Anastomose Cirúrgica/efeitos adversos , Brônquios/cirurgia , Transplante de Pulmão/métodos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Artérias Brônquicas/cirurgia , Feminino , Humanos , Isquemia/epidemiologia , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Taxa de SobrevidaRESUMO
The IL-2, IL-4, and IL-7 signaling pathways have been shown to utilize shared components. The receptors for these cytokines are composed of ligand-specific binding chains that associate with a shared signaling subunit, the common gamma (gamma c) chain. In addition, IL-2, IL-4, and IL-7 induce activation of a common set of nonreceptor tyrosine kinases, Jak-1 and Jak-3. We have further investigated the signaling events induced by these cytokines and find that the gamma c-associated receptors activate distinct signal transducing factors (STFs). In addition, we show that a 94-kDa STAT-related protein (p94) is activated in response to IL-2 and IL-7, but not IL-4. These data indicate that IL-2, IL-4, and IL-7 activate distinct signaling molecules which might be differentially recruited to the receptor complex by the ligand-specific units of the IL-2, IL-4, and IL-7 receptors.
Assuntos
Interleucinas/metabolismo , Receptores de Interleucina/metabolismo , Transdução de Sinais , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular , Humanos , Dados de Sequência Molecular , Fosforilação , Tirosina/metabolismoRESUMO
IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with Stat6 DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R.
Assuntos
Antígenos CD/genética , Antígenos CD/fisiologia , Regulação da Expressão Gênica/imunologia , Interleucina-4/genética , Receptores de Interleucina/genética , Receptores de Interleucina/fisiologia , Sequência de Aminoácidos , Antígenos CD/química , Sequência de Bases , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Divisão Celular/imunologia , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/farmacologia , Interleucina-4/farmacologia , Linfoma de Células B , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Fosforilação/efeitos dos fármacos , Canais de Potássio/farmacologia , Receptores de IgE/biossíntese , Receptores de Interleucina/química , Receptores de Interleucina-4 , Ativação Transcricional , Células Tumorais Cultivadas , Tirosina/análiseRESUMO
The interleukin 4 (IL-4) signaling pathway involves activation, by tyrosine phosphorylation, of two distinct substrates, a signal-transducing factor (STF-IL4) and the IL-4-induced phosphotyrosine substrate (4PS). It is not known whether the IL-4-mediated activation of these substrates occurs via related or distinct signaling pathways. We report that 32D cells, an IL-3-dependent myeloid progenitor cell line in which no phosphorylated 4PS is found, activate high levels of STF-IL4 in response to IL-4. Consistent with the known requirement for 4PS or insulin receptor substrate 1 (IRS-1) in IL-4-mediated mitogenesis, activation of STF-IL4 in 32D cells is not sufficient for IL-4-inducible c-myc expression. In addition, we have examined the ability of 32D cells transfected with different truncation mutants of the human IL-4 receptor to activate Jak-3 kinase and STF-IL4 in response to human IL-4. As in the case of 4PS/IRS-1, we have found that activation of both Jak-3 and STF-IL4 requires the presence of the IL-4 receptor region comprising aa 437-557. The finding that the same region of the IL-4 receptor is required for the induction of both 4PS/IRS-1 and STF-IL4 suggests that the IL-4-stimulated activation of these two substrates might involve common factors.