RESUMO
OBJECTIVE: To clarify the genetic mechanisms underlying intervertebral disc degeneration (IDD), we examined the associations between single-nucleotide polymorphisms (SNPs) and indicated as coefficient of interaction term (IDD) in a general population in Japan. METHODS: This was a cross-sectional study. In 1,605 participants, C2-3 to L5/S1 in the total spine magnetic resonance imaging (MRI) were evaluated using the Pfirrmann's scoring system. Disc scores of 4 and 5 were defined as IDD. Eight SNPs in eight genes associated with IDD were examined at each disc level, considering the non-genetic risk factors of age, sex, and body mass index (BMI). RESULTS: The highest odds ratio was found for rs9406328 in the THBS2 gene at disc level T12-L1 (OR 1.27, 95%CI 1.05 to 1.53), and this association was strengthened after adjustment for age using logistic regression (OR 1.37, 95%CI 1.12 to 1.67). Among participants aged <50 years and 50-59, the average IDD score in those with 2 risk alleles of rs9406328 was markedly higher than in those with 0 or 1 risk allele, and the difference is much wider than the elderly participants. It indicates the genetic effect of rs9406328 is stronger in the younger age groups. Finally, multiple linear regression analyses of the association between rs9406328 and IDD, adjusted for age, sex, and BMI at each disc level, showed a statistical interaction between age and the number of risk alleles at C7-T1, T3-4 and T4-T5 as well as T12-L1. CONCLUSION: CONCLUSION: The association between rs9406328 in THBS2 and IDD was replicated. The contributions of genetic and environmental factors to IDD differed by disc level.
Assuntos
Degeneração do Disco Intervertebral/genética , Polimorfismo de Nucleotídeo Único , Trombospondinas/genética , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
Genotyping graft livers by short tandem repeats after human living-donor liver transplantation (n = 20) revealed the presence of recipient or chimeric genotype cases in hepatocytes (6 of 17, 35.3%), sinusoidal cells (18 of 18, 100%), cholangiocytes (15 of 17, 88.2%) and cells in the periportal areas (7 of 8, 87.5%), suggesting extrahepatic cell involvement in liver regeneration. Regarding extrahepatic origin, bone marrow mesenchymal stem cells (BM-MSCs) have been suggested to contribute to liver regeneration but compose a heterogeneous population. We focused on a more specific subpopulation (1-2% of BM-MSCs), called multilineage-differentiating stress-enduring (Muse) cells, for their ability to differentiate into liver-lineage cells and repair tissue. We generated a physical partial hepatectomy model in immunodeficient mice and injected green fluorescent protein (GFP)-labeled human BM-MSC Muse cells intravenously (n = 20). Immunohistochemistry, fluorescence in situ hybridization and species-specific polymerase chain reaction revealed that they integrated into regenerating areas and expressed liver progenitor markers during the early phase and then differentiated spontaneously into major liver components, including hepatocytes (≈74.3% of GFP-positive integrated Muse cells), cholangiocytes (≈17.7%), sinusoidal endothelial cells (≈2.0%), and Kupffer cells (≈6.0%). In contrast, the remaining cells in the BM-MSCs were not detected in the liver for up to 4 weeks. These results suggest that Muse cells are the predominant population of BM-MSCs that are capable of replacing major liver components during liver regeneration.
Assuntos
Transplante de Medula Óssea , Hepatopatias/cirurgia , Regeneração Hepática/fisiologia , Transplante de Células-Tronco Mesenquimais , Complicações Pós-Operatórias/terapia , Adulto , Animais , Criança , Feminino , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Transplante de Fígado/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos SCID , PrognósticoRESUMO
The aim of this study was to compare the prognosis of separated and non-separated tooth autotransplantation of the upper first and second molars with complete root formation undertaken at dental clinics. The participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. This study analysed 35 separated teeth and 22 non-separated teeth of 47 participants ranging from 27 to 76 years of age (mean age: 55·0 years) after data screening and elimination. The cumulative post-transplantation survival rate at 10 years was 77·1% for separated teeth and 63·6% for non-separated teeth as calculated with the Kaplan-Meier method. There were no significant differences between separated teeth and non-separated teeth in a log rank test (P = 0·687). Separated-tooth autotransplantation can help fill narrow recipient sites and increase occlusal supporting zones, but the clinical success rate was only 48·6%. Although transplantation of teeth with complete root formation has limited prognosis, transplantation of upper first and second molars, whether separated or non-separated, is a viable option to replace missing teeth.
Assuntos
Arcada Parcialmente Edêntula/cirurgia , Dente Molar/transplante , Procedimentos Cirúrgicos Bucais/métodos , Raiz Dentária/transplante , Adulto , Idoso , Feminino , Humanos , Masculino , Maxila/cirurgia , Pessoa de Meia-Idade , Prognóstico , Transplante Autólogo/métodosRESUMO
Gender-related risk factors in the survival of transplanted teeth with complete root formation have not yet been identified. The purpose of this study was to investigate gender differences in tooth autotransplantation at dental clinics. We asked participating dentists to provide information on transplantations they had undertaken from 1 January 1990 to 1931 December 2010. The data were screened to exclude patients who underwent more than one transplantation, smokers or those whose smoking habits were unknown, patients under 30 or who were 70 years old and over, cases where the transplanted teeth had incomplete root formation or multiple roots and those with fewer than 20 present teeth post-operation. We analysed 73 teeth of 73 males (mean age, 47.2 years) and 106 teeth of 106 females (mean age, 45.3 years) in this study. The cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method. The cumulative survival rate for males was 88.3% at the 5-year mark, 64.8% at 10 years and 48.6% at 15 years; for females, it was 97.2% at the 5-year mark, 85.9% at 10 years and 85.9% at 15 years. A log-rank test indicated the difference between males and females to be significant (P = 0.011). There was also a significant difference in the main causes for the loss of transplanted teeth: males lost more transplanted teeth due to attachment loss than females (P < 0.05). These results indicate that males require more attention during the autotransplantation process, particularly at the stage of pre-operation evaluation and that of follow-up maintenance.
Assuntos
Raiz Dentária/anatomia & histologia , Dente/transplante , Adulto , Idoso , Dente Pré-Molar/patologia , Dente Pré-Molar/transplante , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Dente Molar/patologia , Dente Molar/transplante , Odontogênese/fisiologia , Perda da Inserção Periodontal/complicações , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Perda de Dente/etiologia , Transplante Autólogo , Resultado do TratamentoRESUMO
The aim of this study was to investigate risk factors with age in the long-term prognosis of autotransplantation of teeth with complete root formation at dental clinics. Participating dentists were asked to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. The data were screened to exclude patients who were under 25 or 70 years of age and over, those who were smokers or whose smoking habits were unknown, those whose transplanted teeth had incomplete root formation or multiple roots and those with fewer than 25 present teeth post-operation. The participants in this study were 71 men (74 teeth) and 100 women (107 teeth) ranging from 25 to 69 years of age. Third molars were used as donor teeth in 89·0% of the cases. The participants were divided into three age groups of 25-39, 40-54 and 55-69. Survival analysis was conducted using the Kaplan-Meier method, and a log-rank test revealed that there were no significant differences in age groups for men or women. Cox regression analysis indicated that the survival of transplanted teeth was not influenced by age. However, although not statistically significant, the clinical success rate was lower in the 55-69-year-old group than that in the younger groups. These results indicate that if suitable donor teeth are available and the conditions are right, autotransplantation is a viable treatment for missing teeth regardless of the age of the patient.
Assuntos
Raiz Dentária/crescimento & desenvolvimento , Dente/transplante , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Dente Serotino/transplante , Prognóstico , Modelos de Riscos Proporcionais , Transplante AutólogoRESUMO
The aim of this study was to investigate the usage of tooth autotransplantation in dental clinics which offer the treatment and evaluate its practicality. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. A total of 614 teeth from 552 patients (37 dentists) ranging in age from 17 to 79 (mean age: 44·1) were examined. Cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method, and log rank test was used for analysis of factors. The mean number of autotransplantation patients per clinic per year was 1·4. Upper third molars constituted 36·8% of donor teeth, while 37·1% were lower third molars. The lower first molar region was the most common recipient site at 32·6%, followed by the lower second molar region (28·0%). Prosthodontic treatment of transplanted teeth involved coverage with a single crown (72·5%) and abutment of bridge (18·9%). A total of 102 transplanted teeth were lost owing to complications such as attachment loss (54·9%) and root resorption (25·7%). The cumulative survival rate in cases where donor teeth had complete root formation was 90·1% at 5 years, 70·5% at 10 years and 55·6% at 15 years. The mean survival time was 165·6 months. Older age was a significant risk factor (P < 0·05) for survival. In cases where suitable donor teeth are available, autotransplantation of teeth may be a plausible treatment option for dealing with missing teeth in dental clinics.
Assuntos
Procedimentos Cirúrgicos Bucais/estatística & dados numéricos , Dente/transplante , Adolescente , Adulto , Idoso , Clínicas Odontológicas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo/estatística & dados numéricos , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study was to investigate the risk factors affecting long-term prognosis of autotransplantation of third molars with complete root formation in males at dental clinics. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. After data screening and elimination, participants of this study consisted of 183 teeth of 171 males ranging from 20 to 72 years of age (mean age, 44·8 years). The cumulative survival rate was 86·0% at the 5-year mark, 59·1% at 10 years and 28·0% at 15 years. The mean survival time was 134·5 months, as calculated by the Kaplan-Meier method. Single factor analysis using the log-rank test showed that the following factors had significant influence (P < 0·05) on survival of transplanted teeth: periodontal disease as the reason for recipient site tooth extraction, fewer than 25 present teeth and Eichner index Groups B1 to C. Cox regression analysis examined five factors: age, smoking habit, recipient site extraction caused by periodontal disease, fewer than 25 present teeth and Eichner index. This analysis showed that two of these factors were significant: fewer than 25 present teeth was 2·63 (95% CI, 1·03-6·69) and recipient site extraction caused by periodontal disease was 3·80 (95% CI, 1·61-9·01). The results of this study suggest that long-term survival of transplanted teeth in males is influenced not only by oral bacterium but also by occlusal status.
Assuntos
Dente Serotino/transplante , Adulto , Fatores Etários , Idoso , Coroas , Dente Suporte , Cárie Dentária/etiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/etiologia , Periodontite/complicações , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Tratamento do Canal Radicular , Reabsorção da Raiz/etiologia , Fatores Sexuais , Fumar , Análise de Sobrevida , Anquilose Dental/etiologia , Extração Dentária , Fraturas dos Dentes/etiologia , Raiz Dentária/lesões , Alvéolo Dental/cirurgia , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
Activation of Wnt signaling has been implicated in gastric tumorigenesis, although mutations in APC (adenomatous polyposis coli), CTNNB1 (beta-catenin) and AXIN are seen much less frequently in gastric cancer (GC) than in colorectal cancer. In the present study, we investigated the relationship between activation of Wnt signaling and changes in the expression of secreted frizzled-related protein (SFRP) family genes in GC. We frequently observed nuclear beta-catenin accumulation (13/15; 87%) and detected the active form of beta-catenin in most (12/16; 75%) GC cell lines. CpG methylation-dependent silencing of SFRP1, SFRP2 and SFRP5 was frequently seen among GC cell lines (SFRP1, 16/16, 100%; SFRP2, 16/16, 100%; SFRP5, 13/16, 81%) and primary GC specimens (SFRP1, 42/46, 91%; SFRP2, 44/46, 96%; SFRP5, 30/46, 65%), and treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine rapidly restored SFRP expression. Ectopic expression of SFRPs downregulated T-cell factor/lymphocyte enhancer factor transcriptional activity, suppressed cell growth and induced apoptosis in GC cells. Analysis of global expression revealed that overexpression of SFRP2 repressed Wnt target genes and induced changes in the expression of numerous genes related to proliferation, growth and apoptosis in GC cells. It thus appears that aberrant SFRP methylation is one of the major mechanisms by which Wnt signaling is activated in GC.
Assuntos
Carcinoma/genética , Epigênese Genética , Proteínas Proto-Oncogênicas/genética , Neoplasias Gástricas/genética , Proteínas Wnt/genética , Carcinoma/química , Linhagem Celular Tumoral , Ilhas de CpG , Metilação de DNA , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Proto-Oncogênicas/análise , Transdução de Sinais , Neoplasias Gástricas/química , Fatores de Transcrição TCF/antagonistas & inibidoresRESUMO
BACKGROUND: Although percutaneous endoscopic gastrostomy (PEG) is a well-accepted and less invasive method of feeding tube placement in patients with swallowing difficulties, complications and early death after PEG have been reported. AIM: This study aimed to evaluate predictive factors associated with 30-day mortality after PEG, and to assess the utility of nutritional supporting period before PEG in reducing early mortality following PEG. DESIGN: An observational study. METHODS: We retrospectively analyzed 268 patients who underwent PEG at Sapporo Shirakaba-dai Hospital from 2006 to 2010, using clinical and laboratory data to analyze predictive factors associated with early death after PEG. Then, we prospectively assessed 152 consecutive patients assessed for eligibility for PEG from 2011 to 2014. We assessed the patients' nutritional condition using Onodera's prognostic nutritional index (PNI), and supported nutrition for more than 10 days before PEG in patients with a poor nutritional index (PNI < 37). RESULTS: In both univariate and multivariate analyses in the retrospective study, Onodera's PNI of less than 37 was the only predictive factor for early mortality. In the second study, among the 115 patients who finally underwent PEG, early mortality rates improved to 1.7% from 5.2% in the first study. Conversely, 32% of patients with malnutrition who did not undergo PEG died within 30 days. CONCLUSION: Nutritional status might be a predictive factor for early mortality after PEG. In patients with poor nutritional status, nutritional supporting period before PEG might improve the outcomes and reduce unnecessary PEG.
Assuntos
Nutrição Enteral , Gastroscopia , Gastrostomia/mortalidade , Desnutrição/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrostomia/efeitos adversos , Humanos , Japão/epidemiologia , Masculino , Análise Multivariada , Avaliação Nutricional , Estado Nutricional , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida , Fatores de TempoRESUMO
RATIONALE AND OBJECTIVES: To investigate the impact of random survival forest (RSF) classifier trained by radiomics features over the prediction of the overall survival of patients with resectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The dynamic computed tomography data of 127 patients (97 men, 30 women; mean age, 68 years) newly diagnosed with resectable HCC were retrospectively analyzed. After manually setting the region of interest to include the tumor within the slice at its maximum diameter, texture analyses were performed with or without a Laplacian of Gaussian filter. Using the extracted 96 histogram based texture features, RSFs were trained using 5-fold cross-validation to predict the individual risk for each patient on disease free survival (DFS) and overall survival (OS). The associations between individual risk and DFS or OS were evaluated using Kaplan-Meier analysis. The effects of the predicted individual risk and clinical variables upon OS were analyzed using a multivariate Cox proportional hazards model. RESULTS: Among the 96 histogram based texture features, RSF extracted 8 of high importance for DFS and 15 for OS. The RSF trained by these features distinguished two patient groups with high and low predicted individual risk (P=1.1×10-4 for DFS, 4.8×10-7 for OS). Based on the multivariate Cox proportional hazards model, high predicted individual risk (hazard ratio=1.06 per 1% increase, P=8.4×10-8) and vascular invasion (hazard ratio=1.74, P=0.039) were the only unfavorable prognostic factors. CONCLUSIONS: The combination of radiomics analysis and RSF might be useful in predicting the prognosis of patients with resectable HCC.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Tomografia Computadorizada por Raios X , Idoso , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Hepáticas/patologia , Masculino , Invasividade Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
BACKGROUND: Although kidney graft survival within 5 years after transplantation is now achieved in >95% of recipients, chronic graft deterioration remains a factor limiting long-term survival. Chronic nephrotoxicity induced by calcineurin inhibitors (CNIs) is one of the major causes of chronic graft injury; thus, minimization of CNIs by administration of everolimus (EVR) is expected to relieve their toxic effects. METHODS: Fifty-six kidney transplant recipients receiving CNI-based immunosuppression (tacrolimus, n = 34; cyclosporine, n = 22) were analyzed. The average posttransplant period at conversion was 7.4 years and no less than 3 years. Conversion of immunosuppression was accomplished by reducing CNI by 40% in dose and beginning EVR at 1 or 1.5 mg. Changes in graft function were examined, and adverse effects were evaluated. RESULTS: Significant improvement in graft function was observed quickly after EVR administration, and it had persisted for 1 year after conversion as a 7% increase in estimated glomerular filtration rate. No obvious acute rejection was observed. Further analyses concerning "timing of EVR conversion" and "graft function at conversion" were performed. Graft function was significantly improved even in patients with late conversion at 2 to 10 years. The estimated glomerular filtration rate was significantly improved even in patients with poor function. CONCLUSIONS: We concluded that this modification to the immunosuppressive regimen, as expected, reduced CNI nephrotoxicity. Our results showed that even patients with very late conversion or poor graft function also benefited from EVR conversion with CNI minimization.
Assuntos
Inibidores de Calcineurina/efeitos adversos , Everolimo/administração & dosagem , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim , Adulto , Inibidores de Calcineurina/administração & dosagem , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Fatores de Tempo , Transplantes/efeitos dos fármacos , Adulto JovemRESUMO
The aim of this systematic review and meta-analysis was to investigate how parameters related to geometry influence the clinical performance of orthodontic mini-implants (MIs). Systematic searches were performed in electronic databases including MEDLINE, Scopus, Web of Science, Virtual Health Library, and Cochrane Library and reference lists up to March 2016. Eligibility criteria comprised clinical studies involving patients who received MIs for orthodontic anchorage, with data for categories of MI dimension, shape, and thread design and insertion site, and evaluated by assessment of primary and secondary stability. Study selection, data extraction, quality assessment, and a meta-analysis were carried out. Twenty-seven studies were included in the qualitative synthesis: five randomized, eight prospective, and 14 retrospective clinical studies. One study with a serious risk of bias was later excluded. Medium and short MIs (1.4-1.9mm diameter and 5-8mm length) presented the highest success rates (0.87, 95% CI 0.80-0.92). A maximum insertion torque of 13.28Ncm (standard error 0.34) was observed for tapered self-drilling MIs in the mandible, whereas cylindrical MIs in the maxilla presented a maximum removal torque of 10.01Ncm (standard error 0.17). Moderate evidence indicates that the clinical performance of MIs is influenced by implant geometry parameters and is also related to properties of the insertion site. However, further research is necessary to support these associations.
Assuntos
Implantes Dentários , Procedimentos de Ancoragem Ortodôntica/instrumentação , Implantação Dentária , Planejamento de Prótese Dentária , HumanosRESUMO
BACKGROUND: Significance of monitoring adalimumab trough levels and anti-adalimumab antibodies (AAA) for disease outcome in Crohn's disease (CD) patients remained unclear. AIM: To evaluate the association of adalimumab trough levels and AAA at week 26 with clinical remission at week 52, the effect of azathiopurine on AAA and factors influencing trough levels in CD patients in the DIAMOND trial. METHODS: We performed this study using adalimumab trough levels, AAA at week 26 and 6-thioguanine nucleotide (TGN) in red blood cells at week 12. A multiple regression model and receiver operating analysis was performed to identify factors influencing adalimumab trough levels and AAA, and adalimumab thresholds for predicting disease activity. RESULTS: There was a significant difference of adalimumab trough level at week 26 between patients with disease remission and without at week 52 (7.7 ± 3.3 µg/mL vs 5.4 ± 4.3 µg/mL: P <.001). Adalimumab trough level of 5.0 µg/mL yielded optimal sensitivity and specificity for remission prediction (80.2% and 55.6%, respectively). AAA development at week 26 significantly affected remission at week 52 (P = .021), which was strongly associated with adalimumab trough levels. Female gender and increasing body weight were independently associated with low adalimumab trough levels, and female gender was associated with AAA development. A cut-off 6TGN level of >222.5 p mol/8 ×108 RBCs yielded sensitivity (100%) and specificity (60.6%) for AAA negativity. CONCLUSION: Adalimumab trough levels and AAA occurrence were significantly associated with clinical remission. Higher 6TGN affected AAA negativity. The combination therapy is beneficial in some relevant aspects for CD patients. (UMIN Registration No. 000005146).
Assuntos
Adalimumab/sangue , Anti-Inflamatórios/sangue , Anticorpos/sangue , Doença de Crohn/sangue , Adalimumab/imunologia , Adalimumab/farmacocinética , Adalimumab/uso terapêutico , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Quimioterapia Combinada , Feminino , Nucleotídeos de Guanina/sangue , Humanos , Masculino , Mercaptopurina/análogos & derivados , Mercaptopurina/uso terapêutico , Sensibilidade e Especificidade , Tionucleotídeos/sangue , Resultado do TratamentoRESUMO
In the present single center study, we analyzed 277 kidney transplant patients (procedures performed between February 1984 and February 2006) to determine the impact of long-term dialysis on kidney transplant outcomes. Forty-four had been treated prior to renal transplantation with dialysis for more than 10 years (range, 10.0-32.5 years, average, 16.6 years; Group I), while the remaining 233 recipients showed an average end-stage renal disease period of 2.8 years (range, 0-9.8 years; Group II). There were no significant differences in patient survivals between the 2 groups: 97.3% vs 97.4% at 1 year; 85.7% vs 92.4% at 5 years; 85.7% vs 90.7% at 10 years (P = .2347). Five Group I patients died: 2 from infections, 2 from liver dysfunction, and 1 from cerebral bleeding. These causes of death were similar to those among Group II patients. Graft survival was not significantly different between the 2 groups: 95% vs 88.8% at 1 year; 75.5% vs 76.5% at 5 years; 75.5% vs 65.5% at 10 years (P = .6264). Our results suggested that dialysis treatment for more than 10 years did not have negative effects on posttransplantation patient and graft survival.
Assuntos
Transplante de Rim , Diálise Renal , Adulto , Cadáver , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Falência Renal Crônica/terapia , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Diálise Renal/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Doadores de Tecidos/estatística & dados numéricos , Resultado do TratamentoRESUMO
Two forms of a high-molecular-weight proteinase were isolated from rat liver. The purification procedure involved homogenization of the tissue, chromatography on DEAE-cellulose, high-performance liquid chromatography (HPLC: TSK 3000 SWG) and hydroxyapatite chromatography. The breakthrough fraction from the hydroxyapatite column contained the sodium dodecyl sulphate (SDS)- and linoleic acid-activated proteinase, ingensin A, but the other form, ingensin B, which was also activated by SDS and linoleic acid, was bound to the hydroxyapatite and eluted at 200 mM phosphate. A distinct feature of ingensin A was its activation by a brief sonication procedure. The optimum pH of the two forms was 7.5-9.5, and both of them were activated by monovalent cations. Although both enzymes show similar molecular weights of 700,000 on gel filtration, ingensins A and B were separated into a major subunit of 120,000 and subunits of 25,000-35,000, respectively, under the denaturing conditions.
Assuntos
Cisteína Endopeptidases/isolamento & purificação , Endopeptidases/isolamento & purificação , Isoenzimas/isolamento & purificação , Fígado/enzimologia , Complexos Multienzimáticos/isolamento & purificação , Animais , Cromatografia DEAE-Celulose , Cromatografia Líquida de Alta Pressão , Durapatita , Concentração de Íons de Hidrogênio , Hidroxiapatitas/metabolismo , Ácido Linoleico , Ácidos Linoleicos/farmacologia , Substâncias Macromoleculares , Masculino , Peso Molecular , Complexo de Endopeptidases do Proteassoma , Ratos , Ratos Endogâmicos , Dodecilsulfato de Sódio/farmacologiaRESUMO
The enzyme responsible for the succinylleucylleucylvalyltyrosine methylcoumarylamide- (SLLVT-) degrading activity was purified from the postmitochondrial supernatant of rat liver (Yamamoto, T., Nojima, M., Ishiura, S. and Sugita, H. (1986) Biochim. Biophys. Acta 882, 297-304). The enzyme, named ingensin, was activated by saturated fatty acids, especially myristic acid, as well as by unsaturated linoleic acid and arachidonic acid. Although 2-mercaptoethanol activated ingensin 2-fold and p-chloromercuribenzoate and HgCl2 completely inhibited its peptide-hydrolyzing activity, the enzyme is activated by the addition of a thiol-blocking reagent, monoiodoacetic acid. Ingensin was also inhibited by a specific serine proteinase inhibitor, diisopropyl fluorophosphate, but not by a specific cysteine proteinase inhibitor, E-64-c. These results suggest that the enzyme is a serine proteinase with an active thiol group(s) near the active site. We have found that the addition of glycerol and nordihydroguaiaretic acid lowered the extent of its activation by fatty acids as well as its intrinsic peptide-hydrolyzing activity.
Assuntos
Cisteína Endopeptidases/metabolismo , Endopeptidases/metabolismo , Ácidos Graxos/metabolismo , Fígado/enzimologia , Complexos Multienzimáticos/metabolismo , Animais , Catecóis/farmacologia , Citosol/enzimologia , Dimetil Sulfóxido/farmacologia , Glicerol/farmacologia , Iodoacetatos/farmacologia , Ácido Iodoacético , Isoenzimas/metabolismo , Isoflurofato/farmacologia , Masoprocol , Mercaptoetanol/farmacologia , Peso Molecular , Complexo de Endopeptidases do Proteassoma , RatosRESUMO
The sera from patients with human Duchenne (X-linked) progressive muscular dystrophy contain elevated adenylate kinase (ATP: AMP phosphotransferase, EC 2.7.4.3) activities, in addition to their characteristically high creatine kinase (ATP; creatine N-phosphotransferase, EC 2.7.3.2) activities. By agarose gel electrophoresis of human Duchenne dystrophic serum, the presence of an apparently normal human serum adenylate kinase together with a variant species of adenylate kinase was detected. The latter enzyme species appeared, in its mobility, to be similar to that of the normal human liver-type adenylate kinase. The presence of this aberrant liver-type adenylate kinase could also be demonstrated by characteristic (for the liver type) inhibition patterns with P1,P5-di-(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate. On the other hand, by inhibition titrations with an anti-muscle-type adenylate kinase, hemolysates from the erythrocytes of several Duchenne and Becker's dystrophics were found to contain approx. 96% muscle-type adenylate kinase and their serum approx. 97% muscle-type adenylate kinase. These same patients contained approx. 89% M-M type creatine kinase in their serum (by inhibition against anti-human muscle-type creatine kinase) indicative of the presence also of M-B plus B-B type active isoenzymes. All of these data can best be explained by the presence of a variant or mutant adenylate kinase isoenzyme in the dystrophic serum. This isoenzyme appears to resemble the liver type in its inhibition patterns with P1,P5-di(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate, and in its heat stability (compare also the agarose gel electrophoresis pattern); but structurally, it is a muscle type, or derived from a muscle type, as shown immunologically by inhibition reactions with anti-muscle-type adenylate kinase. Whether this is a fetal-type isoenzyme of adenylate kinase will require further investigation.
Assuntos
Adenilato Quinase/sangue , Fosfatos de Dinucleosídeos , Isoenzimas/sangue , Fígado/enzimologia , Distrofias Musculares/genética , Fosfotransferases/sangue , Nucleotídeos de Adenina/farmacologia , Adenilato Quinase/antagonistas & inibidores , Adolescente , Adulto , Criança , Pré-Escolar , Ácido Ditionitrobenzoico/farmacologia , Eletroforese em Gel de Ágar , Feminino , Humanos , Técnicas Imunológicas , Masculino , Distrofias Musculares/enzimologia , Fosfoenolpiruvato/farmacologia , Cromossomo XRESUMO
In this short review the methods of preparation of novel 1,2,4,5-tetraoxacycloalkanes and the related peroxides are summarized, with the emphasis on the usefulness of 1,1-bishydroperoxides as the precursor. Also, their antimalarial activities in vitro and in vivo are discussed.
Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Cicloparafinas/síntese química , Cicloparafinas/farmacologia , Animais , Desenho de Fármacos , HumanosRESUMO
Basiliximab, a chimeric monoclonal antibody against the alpha chain of the interleukin-2 receptor (IL-2R) has been used in renal transplant patients. We monitored sequential blood concentrations of basiliximab in a patient who received a kidney transplant with basiliximab-based immunosuppression together with multiple sessions of plasmapheresis. A 34-year-old man received a living-related kidney transplant with induction immunosuppression including tacrolimus, mycophenolate, methylprednisolone, and basiliximab. Severe antibody-mediated acute rejection lead to a requirement for hemodialysis. Deoxyspergualin was administered for 10 days at a daily dose of 5 mg/kg combined with eight sessions of double filtration plasmapheresis (DFPP). After treatment, the serum creatinine returned to 0.95 mg/dL, and there were no major complications or infections. Sequential basiliximab blood levels of the patient were monitored following transplantation. The serum basiliximab concentration decreased by 72.4% after five consecutive DFPPs, and by 87.6% after eight DFPP sessions. The elimination rate of basiliximab (DeltaBLX) was 6.1% before DFPP, but increased over eight DFPPs to 20.5%. Serum basiliximab concentrations declined to 0.16 microg/mL on day 33, which is below the IL-2R saturation concentration (0.2 microg/mL). Multiple sessions of plasmapheresis using DFPP enhanced the elimination of serum basiliximab at an average elimination rate of 19.1%. In the patient reported on here, the serum basiliximab concentration fell to below the IL-2R saturation level (0.2 microg/mL) within 1 month of living-related kidney transplantation. We recommend that additional basiliximab infusions be considered for cases undergoing more than three plasmapheresis sessions.
Assuntos
Anticorpos Monoclonais/sangue , Rejeição de Enxerto/terapia , Transplante de Rim/imunologia , Plasmaferese , Proteínas Recombinantes de Fusão/sangue , Doença Aguda , Adulto , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/uso terapêutico , Basiliximab , Quimioterapia Combinada , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Doadores Vivos , Masculino , Proteínas Recombinantes de Fusão/farmacocinética , Proteínas Recombinantes de Fusão/uso terapêutico , Diálise RenalRESUMO
Antibody-mediated acute rejection (AbAR) is one of the primary causes of graft impairment in kidney transplant recipients. Deoxyspergualin (DSG), which displays an antiproliferative action against antigen-stimulated B cells inhibiting antibody production, may be effective to rescue AbAR in combination with plasmapheresis by suppressing antibody production and elimination. In the present study, we report our experience with DSG/plasmapheresis therapy for the treatment of AbAR. Five kidney transplant patients experienced a steroid-resistant acute rejection requiring dialysis followed by an AbAR that was confirmed by biopsy and flow cytometry crossmatch (FCXM) results. DSG was administration at 3 mg/kg per day for 10 days with plasmapheresis reduce antidonor antibody. Treatment outcome, effectiveness, and adverse events were examined; in two cases sequential FCXM examinations were performed to evaluate antibody status. All five patients received DSG/plasmapheresis therapy. The number of plasmapheresis treatments ranged from 1 to 9 according to treatment outcomes. Four patients recovered graft function following treatment; whereas one showed no response to the treatment, and the graft was lost. No serious side effects or infections were observed during or after treatment. Monitoring of sequential FCXM correlated with the clinical course. AbAR shows a worse prognosis than cellular rejection. It is refractory to conventional antirejection therapy. In the present study, DSG/plasmapheresis therapy was effective in four of five patients (80%) with AbAR. It may be considered the first choice of treatment for cases of acute humoral rejection.