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1.
Colorectal Dis ; 22(4): 399-407, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31698537

RESUMO

AIM: Preoperative factors predictive of permanent stoma creation were investigated in a long-term follow-up of patients with mid or low rectal cancer. METHOD: We included patients who underwent radical resection for mid or low rectal cancer with available data for preoperative anal function measured by manometry and Faecal Incontinence Severity Index questionnaire between January 2005 and December 2015 in three tertiary referral hospitals. A permanent stoma was defined as a stoma present until the patient's last follow-up visit or death. Preoperative factors that predicted permanent stoma creation were analysed. RESULTS: Over a median follow-up of 57.4 months (range 12-143 months), a permanent stoma was created in 144/577 (25.0%) patients, including 89 (15.4%) who underwent abdominoperineal resection, one (0.2%) who underwent Hartmann's operation without reversal, 15 (2.6%) with a diverting ileostomy at the time of initial sphincter-preserving surgery without undergoing stoma reversal, and 39 (6.8%) who underwent permanent ileostomy formation after sphincter-preserving surgery. Patients with permanent stoma creation had a shorter tumour distance from the anal verge (P < 0.001), larger tumour size (P = 0.020) and higher preoperative Faecal Incontinence Severity Index score (P = 0.020). On multivariable analysis, tumour distance from the anal verge predicted permanent stoma formation (relative risk 0.53 per centimetre increase; 95% confidence interval 0.46-0.60; P < 0.001) but preoperative anal function did not. CONCLUSION: Tumour distance from the anal verge was the only preoperative determinant of permanent stoma creation in rectal cancer patients. These data may help mid and low rectal cancer patients understand the need for permanent stoma.


Assuntos
Neoplasias Retais , Estomas Cirúrgicos , Canal Anal/cirurgia , Estudos de Coortes , Humanos , Ileostomia , Neoplasias Retais/cirurgia
2.
Colorectal Dis ; 21(10): 1175-1182, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31124259

RESUMO

AIM: This study aimed to investigate the association between Twitter exposure and the number of citations for coloproctology articles. METHOD: Original articles from journals using Twitter between June 2015 and May 2016 were evaluated for the following characteristics: publishing journal; article subject; study design; nationality, speciality and affiliation of the author(s); and reference on Twitter. Citation data for these articles were retrieved from Google Scholar (https://scholar.google.com) in January 2018. We performed a univariate analysis using these data followed by a multivariate, logistic regression analysis to search for factors associated with a high citation level, which was defined as accrual of more than five citations. RESULTS: Out of six coloproctology journals listed on the InCites JCR database, three (Diseases of the Colon & Rectum, Colorectal Disease and Techniques in Coloproctology) used Twitter, where 200 (49.5%) out of a total of 404 articles had been featured. Citation rates of articles that featured on Twitter were significantly higher than those that did not (11.4 ± 9.2 vs 4.1 ± 3.1, P < 0.001). In multivariate analysis, Twitter exposure (OR 8.6, P = 0.001), European Union nationality (OR 2.4, P = 0.004), Colorectal Disease journal (OR 3.3, P = 0.005) and systematic review articles (OR 3.4, P = 0.009) were associated with higher citation levels. CONCLUSION: Article exposure on Twitter was strongly associated with a high citation level. Medical communities should encourage journals as well as physicians to actively utilize social media to expedite the spread of new ideas and ultimately benefit medical society as a whole.


Assuntos
Cirurgia Colorretal/estatística & dados numéricos , Fator de Impacto de Revistas , Mídias Sociais/estatística & dados numéricos , Humanos , Análise Multivariada
3.
Curr Mol Med ; 16(9): 829-839, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27889996

RESUMO

PURPOSE: Recently, a different type of microsatellite instability (MSI) instability designated 'elevated microsatellite alterations at selected tetranucleotide repeats' (EMAST) has been reported in several neoplasms, but its clinical implications remain unclear. We aimed to determine the relationships among EMAST, MSI and clinicopathologic characteristics, including oncologic outcomes, in colorectal cancer (CRC). MATERIALS AND METHODS: We evaluated 100 sporadic CRC cases subjected to surgery using five markers (MYCL1, D9S242, D20S85, D8S321, and D20S82) for EMAST and the Bethesda panel for MSI status. Immunohistochemical detection of hMSH3, c-erbB2, EGFR and thymidylate synthase was performed. Clinical characteristics and prognostic relevance were assessed. RESULTS: We identified 22 EMAST-positive tumors (22.0%) and 32 MSI-high (MSI-H) tumors (32.0%). EMAST was more frequent in colon cancer than rectal cancer (p=0.033), and associated with MSI-H phenotype (p<0.001), low expression of hMSH3 (p=0.004), and overexpression of thymidylate synthase (p=0.006). Among the 38 MSI-L tumors, only one (4.5%) showed EMAST. Long-term oncologic results in terms of overall and disease-free survival were similar between EMAST and non-EMAST tumors. CONCLUSION: EMAST is more closely related to MSI-H than MSI-L or MSS status. The clinical and molecular characteristics of EMAST were distinct in terms of tumor location, thymidylate synthase expression, MSI status and hMSH3 expression. Our preliminary findings support the utility of EMAST as a new potential classifier in CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Repetições de Microssatélites/genética , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Fenótipo , Prognóstico
4.
Oncogene ; 35(39): 5106-18, 2016 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-26973248

RESUMO

The expression of immediate early response 3 (IER3), a protein with a short half-life, is rapidly induced by various cellular stimuli. We recently reported that IER3 induces the apoptosis of cervical cancer cells and that its expression is downregulated in patients with cervical cancer. However, the molecular mechanism involved in the rapid degradation of IER3 remains unknown. Here, we demonstrate that MDM2 is an E3 ligase that interacts with IER3 and promotes its ubiquitination, followed by proteasomal degradation. Polyubiquitination of the conserved lysine 60 of IER3 is essential for its degradation. In addition, four and a half LIM domains protein 2 (FHL2) binds to both IER3 and MDM2, allowing for efficient MDM2-mediated IER3 degradation by facilitating an association between MDM2 and IER3. Moreover, IER3 induces cell cycle arrest in cervical cancer cells and its activity is further enhanced in cells in which FHL2 or MDM2 was silenced, thereby preventing IER3 degradation. The E6 and E7 oncoproteins of human papilloma virus 18 regulated IER3 expression. FHL2 expression was significantly higher in the squamous epithelium of cervical carcinoma tissues than in non-cancerous cervical tissues, whereas cervical carcinoma expression of IER3 was downregulated in this region. Thus, we determined the molecular mechanism responsible for IER3 degradation, involving a ternary complex of IER3, MDM2 and FHL2, which may contribute to cervical tumor growth. Furthermore, we demonstrated that FHL2 serves as a scaffold for E3 ligase and its substrate during the ubiquitination reaction, a function that has not been previously reported for this protein.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Proteínas com Homeodomínio LIM/genética , Proteínas de Membrana/genética , Proteínas Musculares/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/patogenicidade , Humanos , Proteínas Oncogênicas Virais/genética , Complexo de Endopeptidases do Proteassoma/genética , Proteólise , Ubiquitinação , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
5.
Orthop Traumatol Surg Res ; 100(8): 967-70, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25453921

RESUMO

There is extension of the Kocher-Langenbeck approach using trochanteric osteotomy for posterior wall fracture extending to acetabular roof, but it exposes to complications such as nonunion, breakage, and heterotopic ossification. The current study introduces a submuscular sliding plate technique. We retrospectively analyzed 13 patients treated with this technique. It is based on conventional method for posterior wall fracture. After reduction of roof fragment with direct visualization, a pre-contoured plate was passed through a submuscular tunnel under the gluteus medius and minimus. A small split incision was performed on the muscles, and screws were inserted with a triple trocar complex safely under fluoroscopic imaging. All patients had fracture union without complications. X-rays results showed anatomical reduction in 10 cases and imperfect reduction in 3 cases. Our results were satisfactory, particularly without heterotopic ossifications despite no prophylactic regimen of NSAID was applied and no neurological complications, so we believe that this technique is a good option for posterior wall fractures extending to the acetabular roof.


Assuntos
Acetábulo/cirurgia , Placas Ósseas , Fraturas do Fêmur/cirurgia , Acetábulo/lesões , Adulto , Idoso , Bases de Dados Factuais , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Resultado do Tratamento
6.
Orthop Traumatol Surg Res ; 99(7): 823-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24095599

RESUMO

BACKGROUND: Accurate positioning of locking screws depends on accurate insertion of the drill sleeve into the locking compression plate (LCP). The purpose of the present study was to determine factors affecting accurate drill sleeve insertion. HYPOTHESIS: Tilting and shallow locking screw holes and combination-type holes make it difficult to insert the drill sleeve in the LCP. MATERIALS AND METHODS: Twenty-seven 3.5mm LCP metaphyseal insertion holes were selected (Philos(®), LPHP(®), DMTP(®), low-band DMTP(®) [Synthes, Solothurn, Switzerland]). Two orthopedic surgeons checked the time taken for accurate insertion of the drill sleeve into the plate. Variables relating to LCP drill sleeve insertion time were analyzed. RESULTS: It took an average 6.6seconds to insert the drill sleeve accurately in the holes. Insertion time increased with the tilt of the screw hole but not with shallowness. Insertion time in combination-type holes was longer (8.8seconds) than in single locking holes (5.6seconds). DISCUSSION: Tilted screw holes and combination-type holes affect the insertion of the drill sleeve into 3.5mm LCPs. LEVEL OF EVIDENCE: Level IV, experimental study.


Assuntos
Placas Ósseas , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/cirurgia , Parafusos Ósseos , Humanos , Pressão , Desenho de Prótese , Reprodutibilidade dos Testes
7.
Univ. psychol ; 12(2): 581-589, may.-agos. 2013. tab
Artigo em Inglês | LILACS | ID: lil-689623

RESUMO

The Williams-Beuren syndrome (SWB), also known as Williams syndrome, is a contiguous gene deletion of the region 7q.11.23. The main clinical characteristics are typical faces, supravalvular aortic stenosis, failure to thrive, short stature, transient neonatal hypercalcemia, delayed language, friendly personality, hyperacusis and intellectual disability. The diagnosis of SWB is confirmed by the detection of micro deletion by different techniques of molecular cytogenetics, FISH, MLPA or polymorphic markers. This study assessed the verbal intelligence quotient (IQ) and performance and visuo-spatial skills in children and adults with WBS. The composed group was of 31 WBS patients (19 M and 12 F), whose ages ranged from 9 to 26 years (M 14.45 y). All patients had the diagnosis confirmed molecularly. The tests used were the WISC-III, WAIS-III and Rey-Osterrieth Complex Figure Test. The results indicated a total IQ ranged from 51 to 86 (M 63): 22 with mild intellectual disability, 4 with moderate intellectual disability, 4 borderlines and 1 below the normal media. All patients had marked visual-spatial deficits. The results suggest nonverbal reasoning, visuo-spatial perception, spatial representation, working memory, motor planning and executive functions are very affected in this group.


El síndrome de Williams-Beuren (SWB), también conocido como síndrome de Williams, es un síndrome de deleción de genes contiguos de la región 7q.11.23. Se caracteriza por dimorfismo facial típico asociado a anomalías cardiovasculares, personalidad amigable, hiperacusia y deficiencia intelectual. El diagnóstico del SWB es confirmado por la detección de microdeleción a partir de las diferentes técnicas de citogenética molecular: FISH, marcadores polimórficos o MLPA. Este estudio evaluó el cociente intelectual verbal y manipulativo, así como las habilidades visuoespaciales en niños y adultos con SWB. El grupo estuvo formado por 31 pacientes con SWB (19 de sexo masculino y 12 de sexo femenino), cuyas edades variaron entre 9 y 26 años (media 14.45 años). Todos los pacientes tenían el diagnóstico confirmado molecularmente. Los test utilizados fueron las escalas WISC-III, WAIS-III y el Test Figuras Complejas Rey-Osterrieth. Los resultados indicaron un cociente intelectual que osciló de 51 a 86 (media 63), distribuido así: 22 con deficiencia intelectual leve, 4 con deficiencia intelectual moderada, 4 limítrofes, 1 en la media inferior. Todos los pacientes presentaron déficit visuoespacial. Los resultados sugieren que el razonamiento no verbal, la percepción visuoespacial, la representación espacial, la memoria de trabajo, la planificación motora y las funciones ejecutivas están muy comprometidos en el grupo estudiado.


Assuntos
Síndrome de Williams , Inteligência
8.
Transplant Proc ; 38(5): 1346-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16797299

RESUMO

Herpes simplex virus (HSV) infection usually occurs in immunocompromised or severely debilitated patients. It is not so common in patients with renal transplants. The diagnosis can only be made histologically. It usually occurs during or shortly after treatment of graft rejection with high-dose steroids. We have recently experienced a case of HSV esophagitis and nephropathy in the renal allograft biopsy, which was identified by histology, immunostaining, and electron microscopy. A 43-year-old woman underwent cadaveric renal transplantation with cyclosporine and prednisolone treatment. Twelve months later, she developed renal insufficiency and proteinuria. Allograft renal biopsy showed some evidence of acute rejection. She was treated with 3 successive days of methylprednisolone (1.0 g/d) intravenously and continued tapering of steroids. Three weeks after steroid pulse therapy, she had throat pain, oral cavity ulcer, dysphagia, and febrile sensation. Esophagoscopy revealed multiple confluent ulcers in the whole esophagus, and biopsy showed enlarged epithelial cells with prominent nuclei. Immunohistochemically, the epithelial cells were positive with a monoclonal antibody to HSV type 1. She was started on acyclovir intravenously, which was continued for a week. After a week, her symptoms began to improve and repeat endoscopy showed no residual esophagitis. A renal allograft infection with HSV can persist in heavily immunosuppressed patients with recurrent rejection episodes. HSV mainly affects tubular cells causing necrosis, a major reason for functional deterioration. A biopsy is required for diagnosis.


Assuntos
Herpes Simples/diagnóstico , Transplante de Rim , Complicações Pós-Operatórias/virologia , Aciclovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Cadáver , Esofagite/virologia , Feminino , Rejeição de Enxerto/virologia , Humanos , Transplante de Rim/imunologia , Transplante de Rim/patologia , Necrose , Doadores de Tecidos
9.
Head Neck ; 23(10): 830-5, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11592229

RESUMO

BACKGROUND: The purpose of this study was to assess the effectiveness of free tissue transfer for treatment of advanced mandibular osteoradionecrosis (ORN) in head and neck cancer patients. METHODS: We reviewed 29 patients who were treated for advanced mandibular ORN by radical resection and reconstruction with free flaps at our institution. All patients had either failed to respond to conservative treatment, including hyperbaric oxygen therapy and debridement or had pathological fracture due to ORN. RESULTS: Twenty-four vascularized bone (17 fibula, five iliac, and two scapula), four rectus abdominis myocutaneous, and one radial forearm fasciocutaneous free flaps were used. The complications occurred in 6 of 29 patients (21%). A total of four flaps (14%) were lost. The mean follow-up was 2 years 9 months. All patients had complete resolution of ORN symptoms. No evidence of ORN recurrence was observed in any patient. CONCLUSION: For advanced osteoradionecrosis of the mandible, radical resection followed by reconstruction using free flap provides a reliable means of obtaining good wound healing with acceptable aesthetic and functional results.


Assuntos
Doenças Mandibulares/cirurgia , Osteorradionecrose/cirurgia , Retalhos Cirúrgicos , Adulto , Idoso , Carcinoma de Células Escamosas/radioterapia , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos
10.
Mol Cell Biol ; 21(20): 7105-14, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11564893

RESUMO

Cell proliferation requires precise control to prevent mutations from replication of (unrepaired) damaged DNA in cells exposed spontaneously to mutagens. Here we show that the modified human DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (R-MGMT), formed from the suicidal repair of the mutagenic O(6)-alkylguanine (6RG) lesions by MGMT in the cells exposed to alkylating carcinogens, functions in such control by preventing the estrogen receptor (ER) from transcription activation that mediates cell proliferation. This function is in contrast to the phosphotriester repair domain of bacterial ADA protein, which acts merely as a transcription activator for its own synthesis upon repair of phosphotriester lesions. First, MGMT, which is constitutively present at active transcription sites, coprecipitates with the transcription integrator CREB-binding protein CBP/p300 but not R-MGMT. Second, R-MGMT, which adopts an altered conformation, utilizes its exposed VLWKLLKVV peptide domain (codons 98 to 106) to bind ER. This binding blocks ER from association with the LXXLL motif of its coactivator, steroid receptor coactivator-1, and thus represses ER effectively from carrying out transcription that regulates cell growth. Thus, through a change in conformation upon repair of the 6RG lesion, MGMT switches from a DNA repair factor to a transcription regulator (R-MGMT), enabling the cell to sense as well as respond to mutagens. These results have implications in chemotherapy and provide insights into the mechanisms for linking transcription suppression with transcription-coupled DNA repair.


Assuntos
Dano ao DNA , Reparo do DNA , Regulação para Baixo , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Receptores de Estrogênio/metabolismo , Transcrição Gênica , Alquilação , Motivos de Aminoácidos , Sequência de Aminoácidos , Western Blotting , Divisão Celular , Citometria de Fluxo , Glutationa Transferase/metabolismo , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Ligação Proteica , RNA Mensageiro/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Técnicas do Sistema de Duplo-Híbrido
11.
Mol Cell Biol ; 18(3): 1660-9, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9488483

RESUMO

DNA lesions that halt RNA polymerase during transcription are preferentially repaired by the nucleotide excision repair pathway. This transcription-coupled repair is initiated by the arrested RNA polymerase at the DNA lesion. However, the mutagenic O6-methylguanine (6MG) lesion which is bypassed by RNA polymerase is also preferentially repaired at the transcriptionally active DNA. We report here a plausible explanation for this observation: the human 6MG repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is present as speckles concentrated at active transcription sites (as revealed by polyclonal antibodies specific for its N and C termini). Upon treatment of cells with low dosages of N-methylnitrosourea, which produces 6MG lesions in the DNA, these speckles rapidly disappear, accompanied by the formation of active-site methylated MGMT (the repair product of 6MG by MGMT). The ability of MGMT to target itself to active transcription sites, thus providing an effective means of repairing 6MG lesions, possibly at transcriptionally active DNA, indicates its crucial role in human cancer and chemotherapy by alkylating agents.


Assuntos
Dano ao DNA , Reparo do DNA , Guanina/análogos & derivados , Mutagênese , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Transcrição Gênica , Alquilantes/farmacologia , Alquilação , Animais , Anticorpos Monoclonais , Sítios de Ligação , Western Blotting , Ciclo Celular , Linhagem Celular , Núcleo Celular/metabolismo , Desoxirribonuclease I/metabolismo , Mapeamento de Epitopos , Epitopos de Linfócito B , Células HeLa , Humanos , Metilnitrosoureia/farmacologia , Coelhos
12.
Am J Kidney Dis ; 32(5): E4, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10074592

RESUMO

Fibrillary glomerulonephritis is an uncommon disease seen in approximately 1% of all native kidney biopsy specimens. We present here a case of a 40-year-old white woman with the rapid loss of graft function secondary to fibrillary glomerulonephritis within 7 days of receiving a living-related renal allograft. This case emphasizes the values of combining urinalysis with prompt allograft kidney biopsy in recipients with an elevated serum creatinine posttransplantation. When one encounters rapidly progressing glomerulonephritis or a pulmonary-renal syndrome in the immediate posttransplantation period, fibrillary glomerulonephritis must be considered in the differential diagnosis. Because of a high recurrence rate and no available treatment to modify a potentially malignant course of this disease, we recommend caution when considering these patients for transplantation.


Assuntos
Mesângio Glomerular/patologia , Glomerulonefrite/diagnóstico , Transplante de Rim , Citoesqueleto de Actina/ultraestrutura , Adulto , Feminino , Glomerulonefrite/etiologia , Glomerulonefrite Membranoproliferativa/diagnóstico , Glomerulonefrite Membranoproliferativa/cirurgia , Humanos , Recidiva , Falha de Tratamento
13.
Biochemistry ; 35(38): 12259-66, 1996 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-8823159

RESUMO

Human O6-methylguanine-DNA methyltransferase (MGMT) repairs DNA by transferring alkyl (R-) adducts from O6-alkylguanine (6RG) in DNA to its own cysteine residue at codon 145 (formation of R-MGMT). We show here that R-MGMT in cell extracts, which is sensitive to protease V8 cleavage at the glutamic acid residues at codons 30 (E30) and 172 (E172), can be specifically immunoprecipitated with an MGMT monoclonal antibody, Mab.3C7. This Mab recognizes an epitope of human MGMT including the lysine 107 (K107) which is within the most basic region that is highly conserved among mammalian MGMTs. Surprisingly, the K107L mutant protein is repair-deficient and readily cleaved by protease V8 similar to R-MGMT. We propose that R-MGMT adopted an altered conformation which exposed the Mab.3C7 epitope and rendered that protein sensitive to protease V8 attack. This proposal could be explained by the disruption of a structural "salt-link" within the molecule based on the available structural and biochemical data. The specific binding of Mab.3C7 to R-MGMT has been compared with the protease V8 method in the detection of R-MGMT in extracts of cells treated with low dosages of methyliodide (SN2) and O6-benzylguanine. Their identical behaviors in producing protease V8 sensitive R-MGMT and Mab.3C7 immunoprecipitates suggest that probably methyl iodide (an ineffective agent in producing 6RG in DNA) can directly alkylate the active site of cellular MGMT similar to O6-benzylguanine. The effectiveness of MeI in producing R-MGMT, i.e., inactivation of cellular MGMT, indicates that this agent can increase the effectiveness of environmental and endogenously produced alkylating carcinogens in producing the mutagenic O6-alkylguanine residues in DNA in vivo.


Assuntos
Alquilantes/farmacologia , Metiltransferases/química , Metiltransferases/metabolismo , Alquilantes/metabolismo , Sequência de Aminoácidos , Anticorpos Monoclonais/imunologia , Sítios de Ligação , Western Blotting , Células Cultivadas , Cisteína/metabolismo , Reparo do DNA , Mapeamento de Epitopos , Guanina/análogos & derivados , Guanina/metabolismo , Guanina/farmacologia , Humanos , Hidrocarbonetos Iodados/metabolismo , Hidrocarbonetos Iodados/farmacologia , Metiltransferases/imunologia , Dados de Sequência Molecular , O(6)-Metilguanina-DNA Metiltransferase , Mutação Puntual , Testes de Precipitina , Conformação Proteica , Proteínas Recombinantes de Fusão/metabolismo , Serina Endopeptidases/metabolismo
14.
Cancer Res ; 54(14): 3726-31, 1994 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-8033092

RESUMO

Cells resist the major mutagenic effects of alkylating agents by the action of O6-methylguanine-DNA methyltransferase (MGMT), which transfers the alkyl (R) group of O6-alkylguanine, produced in DNA by these chemicals, to a cysteine residue in its active site (formation of R-MGMT). We demonstrate that cellular R-MGMT (which represents a record or memory within the cells exposed to these chemicals) can be assayed by its sensitivity toward proteolysis by protease V8. The possible use of this assay for monitoring exposure to alkylating carcinogens was investigated by using cultured cells and a preliminary study with the use of human blood from normal subjects and patients undergoing chemotherapy. Cultured cell experiments show that R-MGMT is sufficiently stable for the monitoring purpose and its level bears a dose-response relationship to the concentrations of the alkylating agent used. Interestingly, experiments with blood from patients undergoing chemotherapy show a gradual formation of R-MGMT in 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and an induced MGMT deficiency in cyclophosphamide-treated patients. The use of this methodology, which allows for the possible quantification of active MGMT (cellular DNA repair capacity) and R-MGMT (recent exposure) simultaneously, in monitoring human exposure to alkylating carcinogens is discussed.


Assuntos
Alquilantes/metabolismo , Carcinógenos/metabolismo , Metiltransferases/metabolismo , Mutagênicos/metabolismo , Adolescente , Adulto , Sequência de Bases , Sítios de Ligação , Pré-Escolar , Relação Dose-Resposta a Droga , Estabilidade Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , O(6)-Metilguanina-DNA Metiltransferase
16.
Transplantation ; 51(2): 324-9, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1994523

RESUMO

A high level of panel-reactive antibodies (PRA) in potential renal transplant recipients is associated with a long waiting time until transplantation and correlates inversely with graft outcome. We report our experience with the employment of immunoadsorption (IA) using a column composed to sepharose-bound staphylococcal protein A (which has a relatively selective affinity for binding IgG compared with other immunoglobulins) to decrease the PRA levels and expedite transplantation in 6 highly sensitized potential renal transplant recipients (1 primary and 5 awaiting second transplants). All patients had PRA levels of greater than or equal to 70% for a duration of 1 year prior to IA. Only patients with antibody specificity localized to 1 or 2 HLA A or B antigens were accepted for the study. IA procedures were performed on alternate days until a twofold decrease in antibody titer had occurred (maximum: 6 procedures). Repeat procedures were initiated if the HLA antibody titer returned to its baseline value. Intravenous cyclophosphamide (CY) (10 mg/kg/day every 3 weeks) and methylprednisolone (MP) (0.5 mg/kg/day) were provided as adjunctive immunosuppression until transplantation. A total of 44 immunoadsorption procedures were performed (27 primary and 17 repeat) with treatment of 2.49 +/- 0.02 plasma volumes per session. Serum IgG concentration decreased 95 +/- 3% and PRA activity decreased 75 +/- 16% after the primary treatment course. Four patients received cadaveric grafts within 3.7 +/- 1.2 months following the last IA procedure. Three grafts are functioning at 1 year, 8 months, and 8 weeks posttransplant. The remaining graft demonstrated primary nonfunction. All four patients had a past positive crossmatch using pre-IA sera with their respective donors. Patients not transplanted exhibited rapid resynthesis of IgG and a return of the PRA towards baseline levels within a few weeks after IA. We conclude that IA can effectively remove HLA antibodies and expedite graft availability in highly sensitized patients.


Assuntos
Soro Antilinfocitário/análise , Isoanticorpos/análise , Transplante de Rim/imunologia , Adulto , Citotoxicidade Imunológica , Feminino , Antígenos HLA/imunologia , Humanos , Imunoglobulina G/análise , Técnicas de Imunoadsorção , Transplante de Rim/métodos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade
17.
Yonsei Med J ; 31(3): 219-24, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2281682

RESUMO

Seventy-nine fiberoptic bronchoscopies were performed in 46 Patients during 2 years in the Intensive Care Unit of Severance Hospital, Yonsei Medical Center. Bronchoscopies were done more than twice in 13 patients. Forty-three bronchoscopies were done through the orotracheal tube in 27 patients, and narcotics and sedatives such as morphine sulfate, diazepam and lorazepam were added with pancuronium bromide during 52 bronchoscopy procedures in 21 patients. Ventilatory support was accomplished by control mode ventilation for 63 bronchoscopies in 37 patients. Twenty-four patients were from the surgical department, and 37 bronchoscopies were performed in 18 patients in a post-thoracotomy state. Twenty-two patients were nonsurgical patients. We performed 48 bronchoscopies in 26 patients to treat lung haziness, 14 bronchoscopies in 3 patients to confirm the operative anastomosis after pneumonectomy or tracheoplasty, and 11 bronchoscopies to confirm the airway patency and vocal cord movement. We obtained good results from 41 bronchoscopies performed for therapeutic purposes and 28 bronchoscopies done for diagnostic purposes. But in 4 patients with pleural effusion and pneumonia, we could not get any improvement in chest X-ray taken after bronchoscopy. We suggested other procedures in 6 patients for diagnosis or treatment, such as suspension laryngoscopy, thoracentesis, ultrasonogram and laser surgery.


Assuntos
Broncoscópios , Tecnologia de Fibra Óptica , Insuficiência Respiratória/diagnóstico , Obstrução das Vias Respiratórias/diagnóstico , Cuidados Críticos , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Insuficiência Respiratória/terapia
18.
Henry Ford Hosp Med J ; 38(4): 246-51, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2086553

RESUMO

A clinical whole organ pancreas transplantation program for patients with insulin-dependent diabetes mellitus complicated by end-stage renal disease was initiated at Henry Ford Hospital in 1987. Five patients have received pancreatic allografts after a previous kidney transplant (phase 1), and six patients had simultaneous pancreas-kidney transplants (phase 2). Ten patients had functioning pancreatic grafts after surgery, and all of them had normal carbohydrate tolerance with appropriate plasma free insulin responses to an oral glucose tolerance test three months after transplantation. As long as 28 months postsurgery six patients remained free of insulin requirements; however, one patient rejected the pancreatic allograft, and three patients died because of cytomegalovirus pneumonia. Two of the latter patients had functioning pancreatic allografts at the time of their demise. These results compare favorably with those of the International Pancreas Transplant Registry which reflects the world experience. Pancreas transplantation is a unique experimental treatment with the potential of restoring euglycemia and improving the prognosis of insulin-dependent diabetic patients.


Assuntos
Injúria Renal Aguda/cirurgia , Diabetes Mellitus Tipo 1/cirurgia , Transplante de Rim , Transplante de Pâncreas , Injúria Renal Aguda/complicações , Injúria Renal Aguda/mortalidade , Causas de Morte , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/mortalidade , Humanos , Transplante de Rim/mortalidade , Transplante de Pâncreas/mortalidade , Período Pós-Operatório , Prognóstico , Transplante Homólogo
19.
Yonsei Med J ; 30(1): 12-5, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2741470

RESUMO

Pulse oximetry is a noninvasive technique for measuring O2 saturation (SpO2) continuously. We applied pulse oximetry to 9 pediatric patients with tetralogy of Fallot during shunt surgery. Arterial oxygen tensions (PaO2) and saturations (SaO2) were also measured at the time of postinduction, just before the shunt, after the shunt and at the end of the operation. The SpO2 and SaO2 levels were identically changed in all 4 periods. The PaO2 was increased a little without statistical significance after the shunt procedure and at the end of the operation compared with the values before the shunt. However, SaO2 values increased with statistical significance after the shunt procedure and SpO2 values also showed similar increases with significance. In conclusion, continuous monitoring of SpO2 by pulse oximetry, instead of PaO2, is a very useful and reliable method to assess the improvement of perfusion after shunt, particularly in cyanotic cases.


Assuntos
Oximetria , Tetralogia de Fallot/cirurgia , Pré-Escolar , Humanos , Lactente , Período Intraoperatório , Oxigênio/sangue , Tetralogia de Fallot/sangue
20.
Curr Surg ; 46(1): 6-9, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2656108

RESUMO

Cadaver kidneys from donors with DIC appear to have an increased incidence of delayed function and primary nonfunction. These kidneys may be safely transplanted if cortical necrosis is ruled out. Heparin, antiplatelet therapy, and withholding of cyclosporin A therapy in the early post-transplantation period may improve renal function if there is evidence of glomerular capillary thrombosis.


Assuntos
Coagulação Intravascular Disseminada/fisiopatologia , Transplante de Rim , Obtenção de Tecidos e Órgãos , Adulto , Cadáver , Coagulação Intravascular Disseminada/cirurgia , Humanos , Necrose do Córtex Renal/complicações , Necrose do Córtex Renal/fisiopatologia , Masculino , Pessoa de Meia-Idade
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