RESUMO
We evaluated virtual crossmatching (VXM) for organ allocation and immunologic risk reduction in sensitized isolated intestinal transplantation recipients. All isolated intestine transplants performed at our institution from 2008 to 2011 were included in this study. Allograft allocation in sensitized recipients was based on the results of a VXM, in which the donor-specific antibody (DSA) was prospectively evaluated with the use of single-antigen assays. A total of 42 isolated intestine transplants (13 pediatric and 29 adult) were performed during this time period, with a median follow-up of 20 months (6-40 months). A sensitized (PRA ≥ 20%) group (n = 15) was compared to a control (PRA < 20%) group (n = 27) to evaluate the efficacy of VXM. With the use of VXM, 80% (12/15) of the sensitized patients were transplanted with a negative or weakly positive flow-cytometry crossmatch and 86.7% (13/15) with zero or only low-titer (≤ 1:16) DSA. Outcomes were comparable between sensitized and control recipients, including 1-year freedom from rejection (53.3% and 66.7% respectively, p = 0.367), 1-year patient survival (73.3% and 88.9% respectively, p = 0.197) and 1-year graft survival (66.7% and 85.2% respectively, p = 0.167). In conclusion, a VXM strategy to optimize organ allocation enables sensitized patients to successfully undergo isolated intestinal transplantation with acceptable short-term outcomes.
Assuntos
Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Teste de Histocompatibilidade/métodos , Intestinos/transplante , Transplante de Órgãos/métodos , Transplante , Adulto , Criança , Pré-Escolar , Isquemia Fria , Feminino , Seguimentos , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Resultado do Tratamento , Listas de EsperaRESUMO
Although receptor-specific refractoriness has been suggested to be one of the regulatory mechanisms of epidermal adenylate cyclase systems, its physiologic significance has been a subject of controversy because of the requirement of unusually high concentrations of agonists to induce refractoriness. In order to determine whether the epidermal adenylate cyclase system is regulated through a refractoriness mechanism by suboptimal concentrations of receptor agonists, this study was undertaken using pig skin epidermal adenylate cyclase systems. Pretreatment of pig skin with 0.1-1 microM epinephrine in vitro resulted in the reduction of the maximal epinephrine response (epinephrine-induced cyclic AMP accumulations) to various degrees without alterations in either low or high Km cyclic AMP phosphodiesterase activities. Repeated pretreatments were shown to be more effective in inducing refractoriness than a single pretreatment. Apparently there was no change in the Km value for epinephrine, suggesting that the decrease in epinephrine response represents a reduction in the number but not in the affinity of functional beta-adrenergic adenylate cyclase receptor sites. This refractoriness by low concentrations of catecholamine pretreatment was specific to the beta-adrenergic system, since there was no reduction in histamine response after the epinephrine pretreatment. These results indicate that the epidermal beta-adrenergic adenylate cyclase system is regulated by much lower concentrations of catecholamine than were previously described. It was suggested that physiologic fluctuations of plasma catecholamine levels might have a profound effect on epidermal beta-adrenergic adenylate cyclase responsiveness, resulting in the alteration of the minimal catecholamine level required for the successive activation of cyclic AMP-dependent protein kinase, which is the predominant target of cyclic AMP in epidermis.
Assuntos
Adenilil Ciclases/metabolismo , Epinefrina/farmacologia , Pele/enzimologia , Animais , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Epinefrina/administração & dosagem , Pele/efeitos dos fármacos , SuínosRESUMO
Effects of colchicine on the epidermal adenylate cyclase systems were investigated. When pig skin (epidermis) was incubated in RPMI 1640 medium without the addition of serum, the beta-adrenergic adenylate cyclase response (epinephrine-induced cyclic AMP accumulations) gradually decreased, whereas adenosine and histamine responses remained high or increased during the long-term (up to 48 h) incubation period. The addition of colchicine (1 mumol/liter) in the incubation medium resulted in an increase in the beta-adrenergic responsiveness and a decrease in adenosine and histamine responsivenesses. The effects of colchicine were both time- and concentration-dependent; they could be observed after 9-12 h incubation, and the maximal effect was obtained at a concentration of 0.1 mumol/liter. Similar effects were observed by the addition of another microtubule-disruptive agent, vinblastine. On the other hand, cytochalasin B, which affects the microfilament system, apparently decreased the beta-adrenergic response and increased adenosine and histamine responses during the long-term incubation period. The addition of serum in the incubation medium resulted in essentially the same effect as that of colchicine; in the presence of serum, colchicine-treated skin responded much more markedly to epinephrine (and much less to adenosine and histamine) than the control skin after 24- and 48-h incubation. Previously we reported that hydrocortisone has similar potentiating effects on the beta-adrenergic system of epidermis. The comparison of the effects of both compounds revealed that colchicine had a stronger effect than hydrocortisone, and furthermore, the simultaneous addition of both compounds (colchicine and hydrocortisone) in the incubation medium resulted in the more marked increase of beta-adrenergic response than the single addition of each chemical. Our overall results, coupled with the finding that hydrocortisone has no toxic effects on the adenosine- or histamine-adenylate cyclase system of epidermis, suggest that colchicine affects epidermal adenylate cyclase systems probably through a mechanism that is independent of glucocorticoid (hydrocortisone) effect.
Assuntos
Colchicina/farmacologia , AMP Cíclico/biossíntese , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Adenosina/farmacologia , Adenilil Ciclases/metabolismo , Animais , Citocalasina B/farmacologia , Epinefrina/farmacologia , Histamina/farmacologia , Hidrocortisona/farmacologia , Suínos , Teofilina/farmacologia , Vimblastina/farmacologiaRESUMO
The effects of protein-synthesis inhibitors (actinomycin D, puromycin, and cycloheximide) on epidermal adenylate-cyclase responses were investigated. When pig skin (epidermis) was incubated in RPMI-1640 medium, the beta-adrenergic adenylate-cyclase response (epinephrine-induced cyclic-AMP accumulations) decreased, whereas the adenosine and histamine responses increased after long-term (up to 48 h) incubation. The addition of actinomycin D or puromycin to the incubation medium resulted in a marked increase in epinephrine-induced cyclic-AMP accumulations and a decrease in adenosine- and histamine-induced cyclic-AMP accumulations. Cycloheximide had a weak effect on the epinephrine response, and had apparently stronger effects on the adenosine and histamine responses than actinomycin D or puromycin. Histologically, various degenerative changes of keratinocytes (with or without acantholytic changes) were observed after long-term incubation with these protein-synthesis inhibitors. Both low- and high-Km cyclic-AMP phosphodiesterase activities were moderately decreased by the protein-synthesis inhibitors. However, augmentation effects on the beta-adrenergic response were also observed in the presence of the cyclic-AMP phosphodiesterase inhibitor, theophylline. We have described previously similar augmentation effects on the beta-adrenergic response caused by glucocorticoids and colchicine. Comparison of the effects of these chemicals with those of protein-synthesis inhibitors revealed that the most marked effects on the beta-adrenergic response were produced by actinomycin D, puromycin and colchicine; glucocorticoid had a moderate effect (hydrocortisone), while cycloheximide had only a weak effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Adenilil Ciclases/metabolismo , Colchicina/farmacologia , Dactinomicina/farmacologia , Glucocorticoides/farmacologia , Puromicina/farmacologia , Pele/enzimologia , Adenosina/farmacologia , Animais , Cicloeximida/farmacologia , Epiderme , Epinefrina/farmacologia , Histamina/farmacologia , Técnicas In Vitro , Pele/citologia , Pele/efeitos dos fármacos , SuínosAssuntos
Imunoglobulinas/análise , Psoríase/imunologia , Pele/imunologia , Adulto , Idoso , Biópsia , Proteínas do Sistema Complemento/análise , Imunofluorescência , Humanos , Imunoquímica , Inflamação/imunologia , Inflamação/patologia , Macrófagos/imunologia , Pessoa de Meia-Idade , Psoríase/patologia , Pele/patologia , Linfócitos T/imunologiaRESUMO
A 5-year-old Japanese boy, who developed dark brown, erythematous lesions (two separate lesions) on his face, scalp, and left upper arm within 2 years, was reported. Biopsy specimens revealed many dilated channels lined by a single layer of endothelial cells without obvious atypicality throughout the dermis. These channels split collagen bundles, giving a "dissection of collagen" appearance. From these clinical and histopathologic findings, we have diagnosed these lesions as acquired progressive lymphangioma. Our patient is the youngest reported patient in the literature, and we were interested in that the two lesions developed separately following previous trauma and they had the tendency to regress following oral prednisolone therapy.
Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Linfangioma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Pré-Escolar , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfangioma/patologia , Masculino , Neoplasias Cutâneas/patologiaRESUMO
A 6-month-old boy with methylmalonic acidemia died of ecthyma gangrenosum caused by systemic Pseudomonas aeruginosa infection. Subtle malnutrition accompanied by the occasional protein restriction treatment may have underlain the development of serious infection in this case.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/complicações , Ectima/etiologia , Ácido Metilmalônico/sangue , Infecções por Pseudomonas/etiologia , Evolução Fatal , Humanos , Lactente , Japão , MasculinoRESUMO
A 64-year-old woman with Lyme disease and manifesting facial nerve palsy had been bitten by a tick on the left frontal scalp 4 weeks previously. Erythema migrans appeared on the left forehead, accompanied by left facial paralysis. Nested polymerase chain reaction-restriction fragment length polymorphism analysis (nested PCR-RFLP) was performed on DNA extracted from a skin biopsy of the erythema on the left forehead. Borrelia flagellin gene DNA was detected and its RFLP pattern indicated that the organism was B. garinii, Five weeks later, B. garinii was isolated by conventional culture from the erythematous skin lesion, but not from the cerebrospinal fluid. After treatment with ceftriaxone intravenously for 10 days and oral administration of minocycline for 7 days, both the erythema and facial nerve palsy improved significantly. Nested PCR and culture taken after the lesion subsided, using skin samples obtained from a site adjacent to the original biopsy, were both negative. We suggest that nested PCR-RFLP analysis might be useful for the rapid diagnosis of Lyme disease and for evaluating therapy.
Assuntos
Grupo Borrelia Burgdorferi/isolamento & purificação , Paralisia Facial/microbiologia , Doença de Lyme/diagnóstico , Adulto , Idoso , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Cefalosporinas/uso terapêutico , Pré-Escolar , DNA Bacteriano/análise , Paralisia Facial/tratamento farmacológico , Feminino , Humanos , Doença de Lyme/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Minociclina/uso terapêutico , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Valor Preditivo dos Testes , Pele/microbiologiaRESUMO
Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus are autoimmune bullous disorders, with tissue-bound and circulating autoantibodies reactive with the noncollagenous NC1 domain of type VII collagen (C-VII). Here, we describe a novel acquired bullous dermatosis with autoantibodies against the triple-helical domain of C-VII. Three patients, all Japanese children, presented with widespread inflammatory tense blisters. Histologically, subepidermal tissue separation was noted with inflammatory infiltrate in the superficial dermis. Direct immunofluorescence staining revealed linear IgG/C3 deposits along the dermal-epidermal junction. Circulating IgG anti-basement membrane zone autoantibodies stained the dermal side of normal skin separated with 1 M NaCl. Direct and indirect immunoelectron microscopy using colloidal gold labeling showed that patient sera reacted with anchoring fibrils. The gold particles were localized both near the lamina densa and on the central banded portion of the fibrils. The sera reacted with C-VII in immunoblots. Epitope analyses with natural and recombinant fragments of C-VII disclosed that the sera did not recognize the NC1 domain of C-VII, but the central triple-helical domain of this anchoring fibril protein. Thus, the present probands show a hitherto unrecognized variant of epidermolysis bullosa acquisita, with autoantibodies against epitopes in the collagenous domain of C-VII.