RESUMO
OBJECTIVE: Familial amyloid polyneuropathy (FAP), which is a fatal disorder inherited in an autosomal dominant fashion, is characterized by systemic accumulation of polymerized transthyretin (TTR) in the peripheral nerves and systemic organs. Liver transplantation has become an accepted treatment of this disorder because it stops the major production of amyloidogenic TTR. However, improved survival of transplant patients compared with that of nontransplant patients has not been sufficiently demonstrated. This study investigated whether transplantation improved the long-term outcome of patients by comparing the survival of patients who had transplantations with that of patients who had not had transplantations. METHODS: Eighty consecutive patients with FAP Val30Met who visited Kumamoto University Hospital between January 1990 and December 2010 were studied. The transplant group consisted of 37 patients who had a partial hepatic graft via living donor transplantation in Japan or who underwent liver transplantation in Sweden, Australia, or the United States. The nontransplant group consisted of 43 patients with FAP. Survival was evaluated by using Kaplan-Meier analysis, and the difference in survival was examined via the log-rank test. RESULTS: The transplant group had prolonged survival (p < 0.001) compared with the nontransplant group. The estimated probability of survival at 10 years was 56.1% for the nontransplant group vs 100% for the transplant group. CONCLUSION: Liver transplantation should be considered as an effective treatment in clinical management of patients with FAP Val30Met. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that liver transplantation prolongs survival in patients with FAP Val30Met.
Assuntos
Neuropatias Amiloides Familiares/mortalidade , Neuropatias Amiloides Familiares/cirurgia , Transplante de Fígado/mortalidade , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Sobreviventes , Resultado do TratamentoRESUMO
The aim of this study was to evaluate serum midkine (S-MK) concentrations as a prognostic tumour marker in oral squamous cell carcinoma (OSCC). We measured S-MK concentrations in patients with OSCC and healthy volunteers. In addition, we performed real-time quantitative reverse transcription-PCR analysis and immunohistochemistry with fresh tumour samples. To determine whether S-MK concentrations have prognostic value, we performed survival analyses with clinical information by using the log-rank test. Serum midkine concentrations were significantly higher in patients with OSCC than in healthy controls (P<0.001). Serum midkine concentrations were also significantly increased in early-stage OSCC compared with those of healthy individuals (P<0.001). In addition, immunohistochemistry allowed identification of overexpressed MK protein in OSCC tissues. MK mRNA showed higher expression in OSCC samples compared with normal mucosal samples. Patients in high S-MK groups showed a significantly lower 5-year survival rate compared with patients in low S-MK groups (P<0.05). The increased S-MK concentrations in early-stage OSCC were strongly associated with poor survival. Serum midkine concentrations may thus be a useful marker not only for cancer screening but also for predicting prognosis of OSCC patients.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Citocinas/sangue , Neoplasias Bucais/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Midkina , Mucosa Bucal/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/sangue , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
This study evaluated the validity of coronary artery bypass grafting (CABG) in patients over 80-year-old investigating the early and late result, patient's opinion to the surgery, and change of activities of daily living scale. From July 1993 to September 2002, consecutive 94 patients over 80-year-old were performed CABG in our institution. The group consisted of 43 female patients, and mean age of 82.6 years. Of these patients, 36 were operated conventional CABG (CABG group) and 58 patients were operated with off-pump CABG (OPCAB) group. There were no significant differences between 2 groups in preoperative characteristics except for anemia and hypertension. Operative results, including mortality, number of distal anastomoses, operative time had no significant differences between 2 groups. But maximum CK-MB fraction was higher in CABG group. There were 4 operative deaths, indicating operative mortality was 4.3%. Late results showed overall survival rate at 3 years was 81.1% and cardiac event free survival rate at 3 years was 88.8%. Questionnaire revealed over 80% patients were satisfied with the surgery but less than 40% patients felt activities of daily living (ADL) scale was improved. Operative results of CABG in octogenarians were satisfied, but more efforts to remain patient's high ADL were mandatory.
Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea/mortalidade , Ponte de Artéria Coronária/mortalidade , Doença das Coronárias/cirurgia , Atividades Cotidianas , Idoso de 80 Anos ou mais , Ponte Cardiopulmonar , Ponte de Artéria Coronária/reabilitação , Ponte de Artéria Coronária sem Circulação Extracorpórea/reabilitação , Doença das Coronárias/mortalidade , Doença das Coronárias/reabilitação , Feminino , Humanos , Masculino , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Heat shock protein 70 (Hsp70) is capable of protecting cells, tissues, organs, and animals from a subsequent, normally lethal heating, as well as from numerous disease states. Therefore, it would be of great therapeutic benefit to discover compounds that are clinically safe yet able to induce Hsp70 in patients. Carbenoxolone, an antiulcer drug, protects gastric mucosal cells against irritants in vivo and in vitro. We assessed here whether carbenoxolone induces Hsp70 expression in human cell lines. We found that carbenoxolone increased the expression of Hsp70 protein and mRNA, and Hsp70 promoter activity.
Assuntos
Antiulcerosos/farmacologia , Carbenoxolona/farmacologia , Proteínas de Choque Térmico HSP70/biossíntese , Western Blotting , Proteínas de Ligação a DNA/biossíntese , Relação Dose-Resposta a Droga , Proteínas de Choque Térmico HSP70/genética , Células HeLa , Fatores de Transcrição de Choque Térmico , Humanos , Regiões Promotoras Genéticas/efeitos dos fármacos , RNA Mensageiro/metabolismo , Fatores de TranscriçãoRESUMO
Notch, Delta and Serrate encode transmembrane proteins that function in cell fate specification in the Drosophila melanogaster embryo. Here we report gene expression patterns and functional characterization of a Xenopus Serrate homolog, X-Serrate-1. The isolated cDNA encoded a transmembrane protein with a Delta/Serrate/LAG-2 domain, 16 epidermal growth factor-like repeats and a cysteine-rich region. Expression of X-Serrate-1 was observed ubiquitously from unfertilized egg to tadpole, but an upregulation occurred in the tailbud stage embryo. Adult expression was found in eye, brain, kidney, heart, spleen and ovary. Whole-mount in situ hybridization revealed that the organ-related expression in eye, brain, heart and kidney occurred from an early stage of rudiment formation. Overexpression of X-Serrate-1 led to a reduction of primary neurons, whereas an intracellularly deleted form of X-Serrate-1 increased the number of primary neurons. Although the function of X-Serrate-1 in primary neurogenesis was quite similar to that of X-Delta-1, expression of X-Serrate-1 and X-Delta-1 did not affect each other. Co-injection experiments showed that wild-type X-Serrate-1 and X-Delta-1 suppressed overproduction of primary neurons induced by dominant-negative forms of X-Delta-1 and X-Serrate-1, respectively. These results suggest that X-Serrate-1 regulates the patterning of primary neurons in a complementary manner with X-Delta-1-mediated Notch signaling.
Assuntos
Proteínas de Membrana/metabolismo , Sistema Nervoso/embriologia , Proteínas/metabolismo , Xenopus laevis/embriologia , Sequência de Aminoácidos , Animais , Proteínas de Ligação ao Cálcio , Clonagem Molecular , Proteínas de Drosophila , Ectoderma/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular , Peptídeos e Proteínas de Sinalização Intracelular , Proteína Jagged-1 , Ligantes , Proteínas de Membrana/genética , Dados de Sequência Molecular , Sistema Nervoso/metabolismo , Proteínas/química , Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Notch , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Proteínas Serrate-Jagged , Transdução de Sinais , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis/genética , beta-Galactosidase/metabolismoRESUMO
The effects of chronic administration of methamphetamine on the pancreas were studied using electron micrography in an experimental model. Methamphetamine (1 mg/kg/day) was subcutaneously injected in five-week-old male Wistar Kyoto rats (WKY) for 8 weeks. Five age and sex-matched WKY served as controls. In light microscopy, scattered necrosis, intercellular vacuolization and severe hemorrhage were the prominent lesions in the methamphetamine-treated rats. The associated ultrastructural alterations consisted of degenerated, swollen, mitochondria with disrupted cristae and cell debris in the superficial space of the endothelial cells, and extensive vacuolization in the degenerated endothelial cells of small vessels and in the smooth muscle cells of their wall. However, in this study, hypercontration or lamellar membrane-like changes were not identified. It is suggested that pancreatic necrotic hemorrhage is a consequence of methamphetamine damage to endothelial cells in various organs, including pancreas.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Metanfetamina/toxicidade , Pâncreas/efeitos dos fármacos , Animais , Endotélio Vascular/ultraestrutura , Masculino , Mitocôndrias/efeitos dos fármacos , Pâncreas/ultraestrutura , Ratos , Ratos Endogâmicos WKYRESUMO
The effects of chronic administration of methamphetamine on pancreatic tissues were histopathologically studied in experimental models. Methamphetamine (1 ml/kg body weight/day) was subcutaneously injected into 14 five-week-old male Wistar Kyoto rats (WKY) for 12 weeks. Age and sex matched 5 WKY rats served as controls. With light microscopy, some scattered edematous lesions and moderate vacuolization were demonstrated in the pancreas of 8 of the methamphetamine treated rats. However, in 4 of the rats, severe regional hemorrhage, partial acinal cell necrosis, destruction of the acinal cells, neutrophile infiltration, interstitial vessel dilatation, interstitial edema and fatty cell invasion were observed after the injections of methamphetamine. In 2 other animals, fibrosis and cirrhosis-like lesions with destruction and degeneration of the acinal cells were observed the small vessels had a slight degeneration of the endothelial cells. In the control animals, no lesions, except for some edematous lesions were found. In all cases, there were no nesidioblastosis-like lesions or necrosis of the Langerhans's islets. In the immunohistochemical study using anti- alpha 1-chymotrypsin antibody, more positive reactive cells were demonstrated among the interstitial and inter acinal cells, both in number and degree, in the methamphetamine treated rats. In addition to the animal model, there were 4 autopsy cases of sudden death in chronic methamphetamine abusers. The autopsies demonstrated a severe acute necrotic hemorrhagic pancreatitis, with only scattered slight hemorrhaging in the brain and lungs. These findings indicate that chronic administration of methamphetamine to rats evoked significant changes in pancreatic tissues including some degeneration of the endothelial cells of the small vessels in this hypoxia-vulnerable organ.