RESUMO
Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR (human framework reassembly) technology. The best variant (61G4) from this screen showed a 3.5-4-fold improvement in neutralization of SARS-CoV infection in vitro. Finally, using a complete site-saturation mutagenesis methodology focused on the CDR (complementarity determining regions), a single point mutation (51E7) was identified that improved the 80% plaque reduction neutralization of the virus by greater than 8-fold. These discovery and evolution strategies can be applied to any emerging pathogen or toxin where a causative agent is known.
Assuntos
Anticorpos Antivirais/isolamento & purificação , Doenças Transmissíveis Emergentes/terapia , Evolução Molecular Direcionada/métodos , Síndrome Respiratória Aguda Grave/terapia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Animais , Anticorpos Antivirais/genética , Anticorpos Antivirais/uso terapêutico , Especificidade de Anticorpos/imunologia , Chlorocebus aethiops , Doenças Transmissíveis Emergentes/prevenção & controle , Descoberta de Drogas , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Mutação Puntual/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Células VeroRESUMO
BACKGROUND: Cervical cancer is the gynecologic malignancy most commonly associated with urinary tract obstruction. Ovarian cancer rarely causes this problem, but when it does, the obstruction is due to impedance of flow in the pelvic ureters. CASE REPORT: A 34 year old female treated by total abdominal hysterectomy with ovarian preservation 9 months earlier for presumed stage IV endometriosis and menorrhagia presented with a recurrent pelvic mass along with symptoms of bladder outlet obstruction. Intravenous urography and computed tomography showed bilateral hydronephrosis and confirmed the bladder outlet obstruction. Laparotomy revealed a large pelvic mass, grossly resembling endometriosis, obstructing the right ureter and impinging upon the urethrovesical junction. Final pathological analysis revealed a mucinous cystadenocarcinoma of the ovary. CONCLUSION: Urinary tract obstruction, including both urethrovesical junction and ureteral obstruction, may be caused by ovarian cancer.
Assuntos
Cistadenocarcinoma Seroso/complicações , Cistadenocarcinoma Seroso/diagnóstico , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Obstrução Ureteral/etiologia , Obstrução do Colo da Bexiga Urinária/etiologia , Adulto , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Histerectomia , Laparotomia , Neoplasias Ovarianas/cirurgia , Obstrução Ureteral/cirurgia , Obstrução do Colo da Bexiga Urinária/cirurgiaRESUMO
The results of treatment with the dermal graft inlay technique for 7 patients with Peyronie's disease and the inability to achieve intercourse are discussed. All 7 patients were unable to attain tumescence postoperatively. We believe that patients who require surgical therapy for Peyronie's disease and who have functional impotence should be treated with silicone penile implants.
