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1.
Transplant Proc ; 48(1): 229-33, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26915873

RESUMO

OBJECTIVE: The use of positron-emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) -labeled islets has been considered to be a potential modality to visualize and quantify early engraftment of islet transplantation. The objective of this study was to evaluate the early islets' survival of the FDG-labeled islets with or without warm ischemic stress in portal transplanted rats using PET and autoradiography. METHODS: Islets were isolated from Lewis rat pancreata with or without 30-minute warm ischemia times (WITs). For islets' labeling, 300 islets were incubated with 3 MBq FDG for 60 minutes. FDG-labeled islets were transplanted into the liver via portal vein. In in vivo study, a PET study was scanned for 90 minutes and the FDG uptake was expressed as percentage of liver injection dose (ID). In ex vivo study, the liver was exposed for 30 minutes with single fluorescence autoradiography. RESULTS: In the PET study, the percentage of liver ID of the islets without WIT was 27.8 and that of the WIT islets was 20.1 at the end of islet transplantation. At 90 minutes after transplantation, the percentage of liver ID was decreased to 14.7 in the islets without WIT and 10.1 in the WIT islets. In the autoradiogram, the number of hot spots was more obviously visualized in the liver transplanted without WIT islets than in the liver transplanted with WIT islets. CONCLUSION: Almost 50% of the islets were immediately lost in both the islets without WIT and those with WIT transplantation in the early period. However, islet survival was 1.4 times higher in the islets without WIT than that in those with WIT in the early engraftment phase.


Assuntos
Autorradiografia/métodos , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/diagnóstico por imagem , Veia Porta/transplante , Tomografia por Emissão de Pósitrons/métodos , Animais , Sobrevivência Celular , Fluordesoxiglucose F18 , Ilhotas Pancreáticas/fisiopatologia , Fígado , Masculino , Compostos Radiofarmacêuticos , Ratos , Ratos Endogâmicos Lew , Coloração e Rotulagem , Transplantes , Isquemia Quente/efeitos adversos
2.
Ann Oncol ; 26(12): 2477-82, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26420428

RESUMO

BACKGROUND: The clinical implementation of genomic profiling for lung cancer with high-throughput, multiplex tests is warranted to allow prioritization of appropriate therapies for individual patients. We have now applied such testing to detect actionable mutations that may inform treatment recommendations in lung cancer. PATIENTS AND METHODS: We prospectively applied amplicon sequencing panels that cover both mutational hotspots in 22 genes related to lung and colon tumorigenesis as well as 72 major variants of ALK, RET, ROS1, and NTRK1 fusion transcripts. We then determined the proportion of patients who received genotype-directed therapy and their overall survival (OS). RESULTS: Tumor specimens from 110 patients with lung cancer recruited between July 2013 and March 2015 were analyzed. The most common genetic alterations were TP53 mutations in 42 patients, followed by EGFR mutations in 25, STK11 mutations in 12, and KRAS mutations in 10. Potentially actionable mutations were identified in 44 patients including 50% of those with adenocarcinoma and 14% of those with squamous cell carcinoma. The OS of patients with advanced or recurrent cancer who had an actionable mutation and received targeted therapy (median OS not achieved) was significantly longer than that of those with no mutation (18.1 months, P = 0.041) or of those with a mutation not so treated (6.1 months, P = 0.0027). CONCLUSIONS: Multiplex genomic testing was performed on formalin-fixed, paraffin-embedded tumor specimens with a success rate of ≥95%. Such testing can assist physicians in matching patients with approved or experimental targeted treatments. CLINICAL TRIAL REGISTRATION: The University Medical Hospital Information Network (UMIN) Clinical Trials Registry under the identifier UMIN000014782.


Assuntos
Tomada de Decisão Clínica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Análise de Sequência de RNA/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros
3.
Transplant Proc ; 46(6): 1913-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25131069

RESUMO

We recently reported that (11)C-methionine positron-emission tomography (PET) is clinically useful for the evaluation of the pancreatic function of the living donor. The objective of this study was to evaluate the postoperative insulin independence in 10 living donor (LD) and 10 brain-dead donor (BD) pancreas transplantations for 20 patients with type I diabetes mellitus by using (11)C-methionine PET. After 6 months, PET/computed tomography was performed 30 minutes after (11)C-methionine (370-740 MBq) injection. The uptake in the pancreas was expressed as the standardized uptake value (SUV). Patient survival rates were 100% at 5 years for LD transplantations and at 2 years for BD transplantations. Insulin independence was 60% for LD transplantations at 5 years and 75% for BD transplantations at 2 years. There were no major surgical complications such as vascular thrombosis, intra-abdominal abscess, and graft pancreatitis. The SUVs for LD and BD pancreas transplantations with insulin independence were 7.2 ± 1.8 and 10.4 ± 2.3, respectively. The SUVs for LD pancreas transplantations with insulin dependence and BD pancreas transplantations with graft failure were 3.6 ± 1.1 and 2.9 ± 1.0, respectively. At 5 years after transplantation, for the LD transplants, the insulin-independent rate was 100% for the graft recipients with an SUV higher than 5, and the median insulin independence duration of the graft recipients with an SUV less than 5 was 7 months (P < .01). The (11)C-methionine PET may be a potent modality to predict long-term insulin independence and the avoidance of pancreas graft failure.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Transplante de Pâncreas , Pâncreas/diagnóstico por imagem , Adulto , Morte Encefálica , Peptídeo C/sangue , Radioisótopos de Carbono , Feminino , Hemoglobinas Glicadas/análise , Humanos , Doadores Vivos , Masculino , Metionina , Pâncreas/fisiologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X
4.
Transplant Proc ; 46(3): 963-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24767391

RESUMO

In the present study, we aimed to compare the pancreas volumetric changes before and after living donor surgery for pancreas transplantation, using three-dimensional (3D) computed tomography (CT) and glucose metabolism. Pancreatic volume (PV) measurement using 3D CT was performed in 13 consecutive donors who underwent distal pancreatectomy for simultaneous living donor pancreas and kidney transplantation. PV was measured using a workstation before and 3 months after living donor operation. As the parameters of glucose metabolism, hemoglobin A1c (HbA1c) level, fasting plasma glucose (FPG) level, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and insulinogenic index (IGI) were examined simultaneously with the PV measurement. The preoperative and postoperative PVs of pancreas was 30 ± 5 mL and 42 ± 9 mL, respectively. The postoperative PV was significantly higher than the preoperative PV (P < .01) and increased by approximately 40% at 3 months after surgery. The postoperative FPG and HbA1c levels were significantly higher than the preoperative values (P < .01). BMI decreased significantly after surgery (P < .01). No differences in HOMA-IR and IGI were noted between before and after surgery. Diabetes mellitus was not observed any of the 13 living donors during this period. Distal pancreatectomy for living donors caused an increase in the PV and maintained insulin resistance, but it was not sufficient to maintain glucose metabolism at the preoperative state.


Assuntos
Glicemia/metabolismo , Doadores Vivos , Transplante de Pâncreas , Pâncreas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão
5.
Transplant Proc ; 46(2): 321-2, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24655953

RESUMO

We have performed retroperitoneoscopic nephrectomy for living kidney donor surgery since 2000. Recently, we introduced single-site retroperitoneoscopic donor nephrectomy (RDN) as a less invasive donor surgery. The procedure was performed in 7 donors (5 women and 2 men) by a single surgeon. The mean age and body mass index of the donors were 62.6 years (range, 53-74 years) and 24.3 kg/m(2) (range, 22.3-29.0 kg/m(2)), respectively. Left-sided nephrectomy was performed in all the donors. The donors were positioned in the right lateral position, and a 7-cm-long incision was made in the left flank. The incision was extended to the retroperitoneal space using the muscle-splitting technique. The retroperitoneal space was then expanded using an inflation balloon. A GelPOINT Advanced Access Platform (Applied Medical, Rancho Santa Margarita, Calif, United States) was placed in the incision. The subsequent technique and equipment were the same as those used in conventional 3-port RDN. The renal artery and vein were dissected using a vascular stapler, and the kidney graft was directly extracted through the incision. The mean operative time was 197 ± 28 minutes, warm ischemic time was 4.1 ± 1.2 minutes, and blood loss was 75 ± 113 mL. No statistical differences were found between the present method and conventional 3-port RDN. Intraoperative and postoperative complications were not observed in any of the donors. Graft function after transplantation was good, and delayed graft function was not observed in any of the recipients. This technique can be easily introduced in the clinical setting by surgeons experienced in RDN.


Assuntos
Transplante de Rim , Doadores Vivos , Nefrectomia/métodos , Segurança do Paciente , Espaço Retroperitoneal/cirurgia , Idoso , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade
6.
Transplant Proc ; 46(2): 372-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24655966

RESUMO

BACKGROUND: Transforming growth factor (TGF)-ß1 may contribute to chronic allograft nephropathy and graft loss; however, the exact molecular mechanism remains unclear. Therefore, we assess the relationship between TGF-ß1 gene polymorphisms, expression, and development of allograft nephropathy. METHODS: We studied 135 renal transplant recipients at our hospital. TGF-ß1 gene polymorphisms (codons 10 and 25) were determined from peripheral blood leukocyte DNA. Plasma TGF-ß1 mRNA was measured by real-time polymerase chain reaction and TGF-ß1 protein levels were assessed by enzyme-linked immunosorbent assay. The relationship between TGF-ß1 genotyping, expression, and rejection and results of renal biopsy were evaluated. RESULTS: The genotype frequency of transplant recipients was 49.6%, 30.4%, and 20.0% for C/T, C/C and T/T at codon 10, 100% for G/G at codon 25, respectively. According to the criteria of Banff '97 classification, 24 cases were classified as acute rejection and whose genotypes were 16, 3, and 5 cases for C/T, C/C and T/T at codon 10. Plasma mRNA expression was elevated in 14 cases and decreased in 8 cases after acute rejection. We measured 267 specimens of TGF-ß1 protein and there was no relation between amount of TGF-ß1 protein and mRNA. CONCLUSION: Our results suggest that the relationship between plasma TGF-ß1 expression and the development of allograft nephropathy remains uncertain. Frequency of allograft rejection differ with TGF-ß1 codon 10 genotypes and the high-risk genotype was different from the reports of other countries.


Assuntos
Transplante de Rim , RNA Mensageiro/genética , Fator de Crescimento Transformador beta1/genética , Feminino , Genótipo , Humanos , Japão , Masculino , Fator de Crescimento Transformador beta1/metabolismo
7.
Transplant Proc ; 46(2): 556-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24656011

RESUMO

PURPOSE: BK polyomavirus-associated nephropathy (BKVAN) is an important cause of renal allograft loss. Immunosuppression therapy in renal transplant recipients can lead to the reactivation of latent BK polyomavirus (BKV) infection, leading to BK viruria and viremia. This single-center study aimed to clarify the association between quantitative measurement of BKV DNA and the progression of BKV infection, and secondly to identify the risk factors associated with the evolution of viruria to viremia. METHODS: We retrospectively analyzed 266 patients who underwent renal transplantation in our center from October 2006 to February 2013. We examined the viral loads of BKV in urine and plasma by quantitative real-time polymerase chain reaction assay after screening all of the recipients by urinary sediment examination. BKVAN was diagnosed by histological examination with immunohistochemistry of the large T antigen in biopsy specimens. RESULTS: Overall, 22 recipients showed BK viruria alone, whereas 22 progressed to BK viremia, of which 6 patients were diagnosed with BKVAN. Among BKVAN patients, 2 cases progressed to graft loss at 59 months and 31 months after diagnosis, respectively. In BKVAN group, the plasma viral loads were significantly higher than those in viremia without nephropathy (P < .001). Multivariate analysis revealed that the evolution of viruria to viremia was associated with recipient age over 55 years (odds ratio, 32.08; 95% confidence interval, 2.1-489.5) and tacrolimus exposure (odds ratio, 11.98; 95% confidence interval, 1.34-107.04). CONCLUSIONS: The progression from viremia to BKVAN was strongly associated with increasing plasma viral loads for BKV DNA. The cutoff value of 1 × 10(4) copies/mL for plasma viral loads could differentiate between BKVAN and viremia alone. Further, recipient age over 55 years and tacrolimus exposure were independently associated with the evolution of viruria to viremia.


Assuntos
Vírus BK/genética , DNA Viral/genética , Transplante de Rim , Infecções por Polyomavirus/complicações , Vírus BK/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral
8.
Transplant Proc ; 46(2): 651-3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24656037

RESUMO

Common iliac artery stenosis after renal transplantation is a rare complication; it can occur in the course of hypertension and renal dysfunction. We report a case of suspected renal allograft rejection with iliac artery stenosis proximal to a transplanted kidney. A 52-year-old man with a history of cadaveric kidney transplantation 26 years previously underwent a second cadaveric kidney transplantation in the left iliac fossa because of graft failure 3 years before. In June 2012, the patient had progressive renal dysfunction. In July, a percutaneous needle biopsy was taken, and it showed no rejection; however, his renal function continued to get worse through September. A percutaneous allograft renal biopsy was performed under ultrasound guidance and showed hyperplasia of the juxtaglomerular apparatus and renin granules. Magnetic resonance angiography was used to evaluate the arteries in the pelvis and showed left common iliac artery stenosis, and a stent was placed. After percutaneous intervention, the patient's ankle brachial pressure index was within the normal range and the allograft function had improved.


Assuntos
Biópsia , Constrição Patológica/diagnóstico , Transplante de Rim , Rim/patologia , Artéria Renal/patologia , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
J Int Med Res ; 39(5): 1941-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22117997

RESUMO

Reactive oxygen species (ROS) and serum ferritin levels are both considered to be important biological factors in the pathogenesis of myelodysplastic syndrome (MDS). This study evaluated the levels of ROS in 40 patients with MDS (19 males and 21 females) using the Free Radical Analytical System, FRAS4, and derivatives of reactive oxygen metabolite kits. The patients' mean age was 67.3 years (range 58 - 86 years). The sera of 34 (85%) patients exhibited higher levels of oxidative stress than the reference range. There was a positive correlation between ROS levels and serum ferritin levels, and a negative correlation between ROS levels and haemoglobin levels. There was a negative relationship between serum haemoglobin and ferritin levels. The results indicated that iron accumulation or severe anaemia could contribute to oxidative stress in MDS patients. Iron chelation and antioxidant therapy may be suitable for the management of MDS.


Assuntos
Ferritinas/sangue , Hemoglobinas/metabolismo , Síndromes Mielodisplásicas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária/sangue , Anemia Refratária/metabolismo , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Estresse Oxidativo , Espécies Reativas de Oxigênio/sangue , Valores de Referência
10.
Cancer Gene Ther ; 18(8): 587-97, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21660064

RESUMO

Although efforts have been made to develop new drugs for infectious and neoplastic diseases utilizing synthetic small interfering RNA(siRNAs), those intrinsically have undesirable effects, including silencing of unintended genes (off-target effect) and nonspecific cytotoxicity. Off-target effects can be avoided by DNA substitution in the guide strand (GS) seed region of nucleotide positions 1-8 and its complementary part of the passenger strand plus the 3' overhang, which is designated as a double-strand RNA-DNA chimera (dsRDC). In this study, we found that the specificity of potent siRNAs targeting human papillomavirus 16 (HPV16) E6 and E7 oncogenes, which we previously reported, could be enhanced by short dsRDC modification (first six nucleotides from the 5' end of the GS and its complementary nucleotides of the passenger strand). Such dsRDC modification reduced nonspecific cytotoxicity in two of three siRNAs (497 and 752), although not in the other (573), which correlated with their off-target effects. In addition, silencing activity was marginally impaired in two dsRDCs (497 and 573) and moderately in one (752). Finally, dsRDC-497 induced E6E7-specific growth suppression of cervical cancer cells as well as E6E7-immortalized human keratinocytes. Our results show that dsRDC modification enhances the specificity of E6E7 siRNA, which is required for use in in vivo settings.


Assuntos
DNA Viral/genética , Papillomavirus Humano 16/genética , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , RNA Interferente Pequeno/genética , RNA Viral/genética , Proteínas Repressoras/genética , Linhagem Celular Tumoral , Quimera/genética , Células HeLa , Humanos , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Interferência de RNA , Proteínas Repressoras/metabolismo , Transfecção
11.
Int J Lab Hematol ; 32(6 Pt 1): e208-16, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20456520

RESUMO

Prediction of the timing of platelet recovery after chemotherapy and hematopoietic stem cell transplantation (HSCT) allows for optimal platelet transfusion. We assessed the clinical utility of the percentage value of the immature platelet fraction (IPF%) monitored using an XE-2100 automated hematology analyzer to predict the timing of platelet recovery after chemotherapy and HSCT. The IPF% was serially monitored in 31 patients with cancer who received 66 courses of chemotherapy and HSCT. In patients with cancer undergoing chemotherapy and HSCT, a transient increase in IPF% was observed 1-11 days prior to platelet recovery (>30 × 109 /l). In patients undergoing chemotherapy with a peak IPF% >10%, platelet recovery occurred significantly earlier than in those with IPF% peak values ≤10% (median periods were 2 and 5 days; P < 0.05). Platelet recovery appears to occur earlier in patients undergoing HSCT with a peak IPF% >10% than in those with IPF% peak values ≤10% (median periods were 2 and 6 days). Thus, the IPF% peak value is a useful parameter for predicting the timing of platelet recovery after chemotherapy and HSCT and has the potential to facilitate optimal platelet transfusion.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias/sangue , Contagem de Plaquetas , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Transfusão de Plaquetas , Reprodutibilidade dos Testes
12.
Transfus Med ; 20(2): 95-103, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19883399

RESUMO

To evaluate the specific reactivity of HLA Class I antibodies (HLA-I Abs) in acute non-hemolytic transfusion reactions (ANHTRs) using solid phase assays (SPAs) and conventional complement-dependent lymphocyte cytotoxicity test (LCT). ANHTRs are major issues in transfusion medicine. Anti-leukocyte antibodies have been implicated as one of the causative agents of transfusion-related acute lung injury (TRALI) and febrile reaction. Antibodies to HLA Class I and/or Class II (HLA Abs) have been intensively studied using SPAs for TRALI, but not for febrile reaction. About 107 patients and 186 donors associated with ANHTRs were screened for HLA Abs by SPAs such as enzyme-linked immunosorbent assay (ELISA) and the Luminex method. When HLA-I Ab was detected, its specific reactivity was evaluated by comparing its specificity identified by the Luminex method using recombinant HLA molecules and cognate HLA antigens (Ags), as well as LCT with or without anti-human globulin (AHG). The incidences of HLA Abs were as high as 32.7% of patients' serum samples and 16% of donors' serum samples. The incidence of HLA-I Abs did not differ significantly between cases of febrile and allergic reactions. However, HLA-I Abs associated with febrile reaction showed a significantly higher rate of possessing specific reactivity to cognate HLA Ags than those associated with allergic reactions. In addition, the Luminex method enabled the detection of HLA-I Abs much earlier than AHG-LCT in serum samples from a patient with febrile reaction and platelet transfusion refractoriness (PTR). SPAs seem more useful than AHG-LCT for evaluating reactivity of antibodies in ANHTR cases.


Assuntos
Lesão Pulmonar Aguda/etiologia , Anafilaxia/etiologia , Febre/etiologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade/métodos , Isoanticorpos/sangue , Reação Transfusional , Urticária/etiologia , Doença Aguda , Lesão Pulmonar Aguda/imunologia , Adulto , Idoso , Anafilaxia/imunologia , Especificidade de Anticorpos , Reações Antígeno-Anticorpo , Criança , Testes Imunológicos de Citotoxicidade , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/imunologia , Fluorometria , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/terapia , Urticária/imunologia
13.
Int J Lab Hematol ; 32(3): 299-306, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19694836

RESUMO

Platelet number is often used as an indicator of the severity of liver disease. Although inadequate thrombopoietin production and decreased platelet production have been proposed as major causes of cirrhotic thrombocytopenia, the underlying mechanism has not yet been fully clarified. We examined whether the measurement of the immature platelet fraction (IPF) in thrombocytopenic patients with liver dysfunction is useful as a rapid and noninvasive method for the differential diagnosis of chronic liver diseases. We examined 20 liver cirrhosis patients, 56 patients with chronic hepatitis, 9 patients with fatty liver, and 86 patients without liver disease. The percentage value of IPF (IPF%) was measured using an XE-2100 multiparameter automatic hematology analyzer. Using a receiver operating characteristic curve, we found diagnostic significance of the absolute platelet count and the absolute number of the IPF between cirrhotic patients and noncirrhotic patients, and developed a powerful multivariate discriminant analysis (MDA) function based on the platelet count and the IPF%. The diagnostic accuracy obtained by the MDA function was superior to that obtained by the absolute number of platelets and the IPF. We therefore propose our IPF% measurement for the diagnosis of liver cirrhosis.


Assuntos
Biomarcadores/sangue , Plaquetas/química , Cirrose Hepática/diagnóstico , Hepatopatias/diagnóstico , Adulto , Idoso , Plaquetas/citologia , Plaquetas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , Curva ROC , Padrões de Referência , Trombocitopenia/diagnóstico
14.
Transplant Proc ; 40(8): 2562-4, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18929801

RESUMO

For the safe operation of living donor pancreas transplantation, we investigated the utility of 11C-methionine positron emission tomography (PET) to examine the function of the residual pancreatic head in patients with pancreatic disease undergoing distal pancreatectomy and in living donors of pancreas transplantation. After 6 hours of fasting, we intravenously injected 370 to 740 MBq 11C-methionine. PET was scanned 30 minutes after injection. 11C-methionine PET uptake by the pancreatic head versus body/tail was expressed as a standardized uptake value (SUV). The SUVs of the pancreatic head were compared before versus after surgery. The SUVs of the pancreatic head in patients before and after distal pancreatectomy were 15.3 +/- 6.0 and 18.2 +/- 2.4, respectively. The SUVs of the pancreatic head in donors before and after distal pancreatectomy were 16.1 +/- 1.0 and 14.7 +/- 1.4, respectively. Both patients and donors showed no significant difference in SUVs of the pancreatic head before and after surgery. However, the SUVs of the residual pancreatic head were elevated after distal pancreatectomy in 80% of patients and 50% of donors. These data indicated that the function of the pancreatic head may be maintained or improved after distal pancreatectomy. 11C-methionine PET may become a potent modality to evaluate segmental pancreatic function for a safe living donor operation.


Assuntos
Doadores Vivos , Transplante de Pâncreas/métodos , Pâncreas/anatomia & histologia , Pancreatectomia/métodos , Transporte Biológico , Radioisótopos de Carbono , Humanos , Metionina/metabolismo , Pâncreas/diagnóstico por imagem , Pâncreas/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Radiografia
15.
Transplant Proc ; 40(8): 2565-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18929802

RESUMO

We performed the first case of simultaneous pancreas and kidney transplantation from a living donor (LDSPK) in 2004. We examined the quality of life (QOL) of performed 6 recipients and 5 donors among 8 LDSPK from 2004 to 2007 at our institution using Short Form 36. All recipients achieved insulin and hemodialysis independence after LDSPK with positive serum C-peptide levels. Before LDSPK, all scores of the 8 specific domains of the recipients were low (28.2 +/- 10.6), indicating extremely poor QOL. Both the Physical and the Mental Component Summary Scores (PCS/MCS) quickly increased after LDSPK. PCS at 6, 12, and 24 months after LDSPK were significantly higher than the pretransplantation level. MCS were also significantly higher than the pretransplantation level. LDSPK showed prominent QOL improvement for the recipient. Complications were not observed in any donor. Although PCS decreased at 6 months after the operation, it recovered at 12 and at 24 months after the operation. MCS was maintained at more than 50 from 6 to 24 months after the operation. QOL was well preserved in the LDSPK donors despite the major surgery. In conclusion, LDSPK was confirmed to be a potent tool for treatment of type 1 diabetes mellitus patients with end-stage renal disease (ESRD) by complete normalization of glucose metabolism and renal function. In addition to these medical advantages, both their physical and mental QOL were improved by LDSPK.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/fisiologia , Transplante de Pâncreas/fisiologia , Qualidade de Vida , Adulto , Pai , Feminino , Humanos , Insulina/uso terapêutico , Transplante de Rim/psicologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Mães , Nefrectomia/métodos , Transplante de Pâncreas/psicologia , Pancreatectomia/métodos , Diálise Renal , Inquéritos e Questionários
16.
Transplant Proc ; 40(8): 2568-70, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18929803

RESUMO

We performed 6 islet transplantations in 4 type 1 diabetes mellitus patients. From September 2003 to April 2007, 23 islet isolations were performed from pancreata of non-heart-beating donors. The pancreata preserved using a 2-layer method or simple cold storage in University of Wisconsin solution were transferred to our cell processing center. The islet isolation was performed according to the Edmonton protocol with some modifications. The immunosuppressive protocol was achieved using sirolimus, tacrolimus, and anti-CD25 antibody (basiliximab). Islet yield was 400 to 491,040 IEQ and purity was 1% to 70%. Stimulation indices upon static incubation were 1.38 to 11.69. All patients who underwent islet transplantation showed positive serum C-peptide levels immediately after transplantation. Although insulin independence was not achieved, they displayed stabilized blood glucose levels, reduced insulin doses, and disappearance of hypoglycemic unawareness. Although stomatitis and diarrhea due to the side effects of sirolimus were observed in 2 patients, there were no severe complications. In patient 1, serum C-peptide levels decreased gradually from 1 year after transplantation. In conclusion, successful islet transplantation was possible using islets isolated from the pancreata of non-heart-beating donors. Further improvements are needed to achieve prolonged graft survival.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Transplante das Ilhotas Pancreáticas/métodos , Glicemia/metabolismo , Cadáver , Separação Celular , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Quimioterapia Combinada , Humanos , Imunossupressores/uso terapêutico , Ilhotas Pancreáticas/citologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Doadores de Tecidos
17.
Transplant Proc ; 40(7): 2289-91, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18790214

RESUMO

ABO-incompatible kidney transplantation has become a popular alternative to kidney transplantation in Japan because of the severe shortage of cadaveric donors. In our institution, 21 cases of ABO-incompatible kidney transplantation were performed from April 2004, to October 2007. Recipient age was 42.8 +/- 14.5 years old; there were 9 men and 12 women. Duration of hemodialysis was 1,914 +/- 2,343 days. Donor operation was performed using a complete laparoscopic procedure. Recipient's splenectomy was performed using a hand-assisted laparoscopic procedure and kidney transplantation was performed with a standard method using an extraperitoneal approach. Pretransplant immunosuppressive protocol includes an administration of mycophenolate mofetil, tacrolimus, predonisolone, splenectomy, double filtration plasmapheresis (DFPP), and plasma exchange (PE). All patients showed an immediate graft function and their serum creatinine levels promptly decreased to 1.48 +/- 0.99 mg/dL on day 7 and 1.21 +/- 0.72 mg/dL on day 30. Both immunoglobulin (Ig)M and IgG titers were maintained at much lower levels for 7 days after transplantation in all patients. Cytomegalovirus antigenemia was observed in 11 patients (52.4%). One patient (4.8%) developed a Pneumocystis Carinii pneumonia and the formation of lymphocele was observed in one patient (4.8%). Total patient survival at 3 years was 95.2%, and graft survival at 3 years was 90.5%, which were almost equal to those in the patients who underwent ABO-matched, compatible kidney transplantation.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos , Sobrevivência de Enxerto/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim/imunologia , Cadáver , Humanos , Isoanticorpos/sangue , Transplante de Rim/mortalidade , Doadores Vivos , Estudos Retrospectivos , Análise de Sobrevida , Doadores de Tecidos , Resultado do Tratamento
18.
Transplant Proc ; 40(7): 2416-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18790253

RESUMO

Reversible posterior leukoencephalopathy syndrome (RPLS) is one of the important side effects of calcineurin inhibitors (CNIs). Magnetic resonance imaging (MRI) of the brain is useful for the diagnosis of RPLS, showing the edema primarily in the cortex and subcortical white matter of the posterior brain regions. Interruption of CNIs is essential for the treatment of patients with RPLS. Herein we have described 2 cases (1.7%) of RPLS induced by CNIs after kidney transplantation. The first case was a 56-year-old man with chronic renal failure due to diabetic nephropathy who received a living-related kidney transplantation in 2006. Initial immunosuppressive therapy consisted of cyclosporine, mycophenolate mofetil (MMF), prednisolone, and basiliximab. Four months after transplantation, he developed unconsciousness and paralysis. The second case was a 24-year-old woman with end-stage renal disease due to Alport syndrome who received an ABO-incompatible living-related kidney transplantation. Initial immunosuppressive therapy consisted of tacrolimus, MMF, prednisolone, and basiliximab. On postoperative day 3, she developed convulsions and unconsciousness. In both patients, RPLS was diagnosed with neurological symptoms and MRI findings at early stage of the disease, and they recovered rapidly from the disease by the interruption of CNIs. Our data demonstrated that early diagnosis and immediate interruption of CNIs were essential for the treatment of RPLS after kidney transplantation.


Assuntos
Inibidores de Calcineurina , Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Ácido Micofenólico/análogos & derivados , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Adulto , Encéfalo/patologia , Feminino , Humanos , Falência Renal Crônica/cirurgia , Doadores Vivos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Nefrite Hereditária/cirurgia , Síndrome da Leucoencefalopatia Posterior/patologia
19.
Food Chem Toxicol ; 46(6): 2190-200, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18381228

RESUMO

The beneficial effects of tea catechins are well documented. We evaluated the genotoxic potential of a green tea catechin preparation using established genotoxicity assays, including a bacterial reverse mutation assay (Ames test), a chromosomal aberration assay in cultured Chinese hamster lung cells (CHL/IU), a mouse lymphoma L5178Y/tk assay, and a bone marrow micronucleus (MN) assay in ICR CD mice and SD rats. No significant increases in the number of revertant colonies were observed in the Ames test, but positive responses were observed in two in vitro assays: the chromosomal aberration assay and mouse lymphoma L5178/tk assay. However, the in vivo study demonstrated no significant increase in micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of both ICR CD mice and SD rats administered a high dose of the green tea catechin preparation up to 2000mg/kg. Combined with favorable epidemiological information suggesting a chemopreventive effect of tea catechins on carcinogenesis, we conclude that green tea catechin presents no significant genotoxic concern under the anticipated conditions of use. These results are consistent with other genotoxicity studies of tea catechins, which show minimal, if any, genotoxic potential.


Assuntos
Catequina/toxicidade , Mutagênicos , Chá/química , Animais , Células da Medula Óssea/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Aberrações Cromossômicas/efeitos dos fármacos , Cricetinae , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos ICR , Testes para Micronúcleos , Testes de Mutagenicidade , Ratos , Ratos Sprague-Dawley , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Timidina Quinase/genética
20.
Cancer Gene Ther ; 15(3): 140-53, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18157144

RESUMO

Persistent infection by high-risk types of human papillomaviruses (HPV) is a necessary cause of cervical cancer, with HPV16 the most prevalent, accounting for more than 50% of reported cases. The virus encodes the E6 and E7 oncoproteins, whose expression is essential for maintenance of the malignant phenotype. To select efficacious siRNAs applicable to RNAi therapy for patients with HPV16+ cervical cancer, E6 and E7 siRNAs were designed using siDirect computer software, after which 10 compatible with all HPV16 variants were selected, and then extensively examined for RNAi activity and specificity using HPV16+ and HPV16-cells. Three siRNAs with the highest RNAi activities toward E6 and E7 expression, as well as specific and potent growth suppression of HPV16+ cancer cells as low as 1 nM were chosen. Growth suppression was accompanied by accumulation of p53 and p21(WAF1/CIP1), as well as morphological and cytochemical changes characteristic of cellular senescence. Antitumor activity of one of the selected siRNAs was confirmed by retarded tumor growth of HPV16+ cells in NOD/SCID mice when locally injected in a complex with atelocollagen. Our results demonstrate that these E6 and E7 siRNAs are promising therapeutic agents for treatment of virus-related cancer.


Assuntos
Papillomavirus Humano 16/genética , Proteínas Oncogênicas Virais/genética , RNA Interferente Pequeno/genética , Proteínas Repressoras/genética , Neoplasias do Colo do Útero/terapia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Senescência Celular/genética , Senescência Celular/fisiologia , Feminino , Terapia Genética/métodos , Células HeLa , Papillomavirus Humano 16/crescimento & desenvolvimento , Humanos , Immunoblotting , Luciferases/genética , Luciferases/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas E7 de Papillomavirus , RNA Interferente Pequeno/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Transfecção , Carga Tumoral , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Ensaios Antitumorais Modelo de Xenoenxerto
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