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1.
J Nippon Med Sch ; 91(1): 10-19, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38233127

RESUMO

Laparoscopic surgery is performed worldwide and has clear economic and social benefits in terms of patient recovery time. It is used for most gastrointestinal surgical procedures, but laparoscopic surgery for more complex procedures in the esophageal, hepatobiliary, and pancreatic regions remains challenging. Minimally invasive surgery that results in accurate tumor dissection is vital in surgical oncology, and development of surgical systems and instruments plays a key role in assisting surgeons to achieve this. A notable advance in the latter half of the 1990s was the da Vinci Surgical System, which involves master-slave surgical support robots. Featuring high-resolution three-dimensional (3D) imaging with magnification capabilities and forceps with multi-joint function, anti-shake function, and motion scaling, the system compensates for the drawbacks of conventional laparoscopic surgery. It is expected to be particularly useful in the field of hepato-biliary-pancreatic surgery, which requires delicate reconstruction involving complex liver anatomy with diverse vascular and biliary systems and anastomosis of the biliary tract, pancreas, and intestines. The learning curve is said to be short, and it is hoped that robotic surgery will be standardized in the near future. There is also a need for a standardized robotic surgery training system for young surgeons that can later be adapted to a wider range of surgeries. This systematic review describes trends and future prospects for robotic surgery in the hepatobiliary-pancreatic region.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/tendências , Laparoscopia/métodos , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Pâncreas/cirurgia , Fígado/cirurgia , Imageamento Tridimensional/métodos , Curva de Aprendizado , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/tendências
2.
Clin J Gastroenterol ; 17(2): 205-210, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38281289

RESUMO

The incidence of esophagogastric junction cancer has been increasing, leading to growing interest in surgical treatment. Leriche syndrome, characterized by occlusion limited to the infrarenal aorta, has not been reported to be associated with ischemic enteritis, and there are no previous reports on the surgical approaches for esophagogastric junction cancer in this disease.We describe the case of a male patient in his fifties with lower abdominal pain and melena who was diagnosed with esophagogastric junction cancer, Leriche syndrome, and ischemic enteritis. Contrast-enhanced computed tomography (CT) showed a hemorrhage from the cancer, occlusion of the abdominal aorta beyond the renal artery branches, and rectal contrast deficiency. Three-dimensional (3D)-CT angiography revealed occlusion from the lumbar artery bifurcation to the distal portions of both common iliac arteries plus numerous collateral pathways, indicating a precarious rectal blood supply. Based on 3D-CT angiography, minimally invasive surgery (MIS) using laparoscopy and thoracoscopy for esophagogastric junction cancer was performed after whole-body control. The patient was discharged without any postoperative complications.Esophagogastric junction cancer with Leriche syndrome can be complicated by ischemic enteritis due to tumor bleeding and fragile collateral pathways. MIS using laparoscopy and thoracoscopy guided by 3D-CT angiography can be safely performed for this disease.


Assuntos
Enterite , Síndrome de Leriche , Neoplasias , Humanos , Masculino , Síndrome de Leriche/complicações , Síndrome de Leriche/cirurgia , Reto , Junção Esofagogástrica/cirurgia , Isquemia , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias/complicações
3.
J Nippon Med Sch ; 90(4): 308-315, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37690822

RESUMO

Development of surgical support robots began in the 1980s as a navigation and auxiliary device for endoscopic surgery. For remote surgery on the battlefield, a master-slave-type surgical support robot was developed, in which a console surgeon operates the robot at will. The da Vinci surgical system, which currently dominates the global robotic surgery market, received United States Food and Drug Administration and regulatory approval in Japan in 2000 and 2009 respectively. The latest, fourth generation, da Vinci Xi has a good field of view via a three-dimensional monitor, highly operable forceps, a motion scale function, and a tremor-filtered articulated function. Gastroenterological tract robotic surgery is safe and minimally invasive when accessing and operating on the esophagus, stomach, colon, and rectum. The learning curve is said to be short, and robotic surgery will likely be standardized soon. Therefore, robotic surgery training should be systematized for young surgeons so that it can be further standardized and later adapted to a wider range of surgeries. This article reviews current trends and potential developments in robotic surgery.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Robóticos , Robótica , Estados Unidos , Humanos , Estômago , Reto
4.
Dis Esophagus ; 36(9)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607133

RESUMO

Esophageal cancer patients require enteral nutritional support after esophagectomy. Conventional feeding enterostomy to the jejunum (FJ) is occasionally associated with small bowel obstruction because the jejunum is fixed to the abdominal wall. Feeding through an enteral feeding tube inserted through the reconstructed gastric tube (FG) or the duodenum (FD) using the round ligament of the liver have been suggested as alternatives. This meta-analysis aimed to compare short-term outcomes between FG/FD and FJ. Studies published prior to May 2022 that compared FG or FD with FJ in cancer patients who underwent esophagectomy were identified via electronic literature search. Meta-analysis was performed using the Mantel-Haenszel random-effects model to calculate Odds Ratios (ORs) with 95% confidence intervals (CIs). Five studies met inclusion criteria to yield a total of 1687 patients. Compared with the FJ group, the odds of small bowel obstruction (OR 0.09; 95% CI, 0.02-0.33), catheter site infection (OR 0.18; 95% CI, 0.06-0.51) and anastomotic leakage (OR 0.53; 95% CI, 0.32-0.89) were lower for the FG/FD group. Odds of pneumonia, recurrent laryngeal nerve palsy, chylothorax and hospital mortality did not significantly differ between the groups. The length of hospital stay was shorter for the FG/FD group (median difference, -10.83; 95% CI, -18.55 to -3.11). FG and FD using the round ligament of the liver were associated with lower odds of small bowel obstruction, catheter site infection and anastomotic leakage than FJ in esophageal cancer patients who underwent esophagectomy.


Assuntos
Neoplasias Esofágicas , Ligamentos Redondos , Feminino , Humanos , Nutrição Enteral , Gastrostomia , Jejunostomia/efeitos adversos , Esofagectomia/efeitos adversos , Fístula Anastomótica/cirurgia , Duodenostomia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fígado/cirurgia , Ligamentos Redondos/cirurgia , Neoplasias Esofágicas/cirurgia
5.
Gan To Kagaku Ryoho ; 46(8): 1315-1317, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501378

RESUMO

We report synchronous resection of gallbladder hyperplasia polyps with pancreaticobiliary maljunction without dilation of the bile duct and sigmoid colon carcinoma. The patient was a 60-year-old woman diagnosed with sigmoid colon cancer. Gallbladder polyps were detected incidentally during a preoperative examination for sigmoid colon cancer that was discovered because of anemia. Detailed examination revealed a suspected gallbladder carcinoma along with pancreaticobiliary maljunction without dilation of the bile duct. The patient underwent synchronous open colectomy and cholecystectomy. Histopathological diagnosis excluded gallbladder carcinoma, so we did not perform bile duct resection or lymph node resection around the bile duct. The final diagnosis was gallbladder hyperplasia polyps, chronic cholecystitis, and sigmoid colon cancer (pT3N2M0, stage Ⅲb). Therefore, physicians should pay attention to the possibility of pancreaticobiliary maljunction if gallbladder polyps are detected incidentally during preoperative examination for other diseases. In the present case, we could treat the patient with minimally invasive techniques by adding the treatment to that performed for the other disease.


Assuntos
Neoplasias da Vesícula Biliar , Neoplasias do Colo Sigmoide , Ductos Biliares , Colo Sigmoide , Dilatação , Feminino , Humanos , Hiperplasia , Pessoa de Meia-Idade , Ductos Pancreáticos
6.
Jpn J Radiol ; 37(8): 605-611, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31256316

RESUMO

PURPOSE: A transomental hernia (TOH) is a rare type of internal hernia and is associated with a high strangulation rate and high mortality rate. Displacement of the transverse colon on computed tomography (CT) may be specific to a TOH and may facilitate an early diagnosis. The aim of this study was to verify the effectiveness of a novel approach assessing displacement of the transverse colon for the preoperative diagnosis of a TOH. MATERIALS AND METHODS: We retrospectively reviewed the CT and operative data of 113 patients who underwent surgery for small bowel obstruction (SBO) between 2011 and 2018. The proportion of transverse colon loops posterior to dilated intestinal loops (PTPI) was calculated. RESULTS: The patients were divided into a TOH group (n = 7) and other SBO group (n = 106). The median PTPI was significantly higher in the TOH group than in the other SBO group (67% [0-97%] vs. 0% [0-100%], Wilcoxon's test, p = 0.03). A receiver operating characteristic curve showed that when the PTPI was ≥ 57%, its sensitivity and specificity for a TOH were 71% and 94%, respectively. CONCLUSION: The PTPI is a reliable quantitative measure to distinguish a TOH from other types of SBOs.


Assuntos
Colo Transverso/diagnóstico por imagem , Hérnia Abdominal/complicações , Hérnia Abdominal/diagnóstico por imagem , Obstrução Intestinal/diagnóstico por imagem , Cuidados Intraoperatórios/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
7.
Case Rep Surg ; 2018: 6145903, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29682388

RESUMO

Granulomatosis with polyangiitis (GPA) is known as anti-neutrophil cytoplasmic antibody- (ANCA-) associated small vessel vasculitis and typically manifests as pulmonary-renal syndrome, but the disease is not limited to pulmonary or renal systems. The inflammation can involve whole body organs. In addition, the ANCA titer does not always become positive. Here, we describe the case of a 91-year-old man who presented with umbilical pain and fever of unknown origin. Only the increased computed tomography value of the greater omentum suggested intra-abdominal inflammation; however, serological examinations, including the ANCA level, could not reveal the focus or cause of symptoms. Finally, the histopathological examination of specimens surgically excised from the greater omentum demonstrated GPA limited to the greater omentum. This report reminds physicians to consider GPA in the differential diagnosis of acute abdominal pain or fever of unknown origin.

8.
Case Rep Med ; 2018: 3258141, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29560005

RESUMO

INTRODUCTION: Annular pancreas is a rare congenital abnormality characterized by a ring of pancreatic tissue surrounding the descending portion of the duodenum. Annular pancreas coexisting with replaced common hepatic artery which is also a rare anatomical variation has not been reported previously. CASE PRESENTATION: A 53-year-old man visited our hospital complaining of epigastric pain. Based on radiological examinations, he was diagnosed as having pancreatitis, annular pancreas, and hepatomesenteric trunk. One month later, obstructive jaundice developed. Endoscopic examination revealed ampullary region carcinoma. We performed pancreaticoduodenectomy using the "artery-first" approach. DISCUSSION: Both annular pancreas and common hepatic artery anomaly are rare. High-quality preoperative imaging and awareness of such rare conditions are necessary for operative safety. Although the embryological relationship between these anomalies is uncertain, the present case may suggest some relevance between the two. CONCLUSION: The "artery-first" approach may be a useful method for pancreaticoduodenectomy in patients who have an anatomical abnormality.

9.
Surg Case Rep ; 4(1): 11, 2018 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-29368097

RESUMO

BACKGROUND: Adult-onset type II citurullinemia is an autosomal recessive disorder characterized by recurrent encephalopathy with hyperammonemia resulting from high plasma citrulline and ammonium levels. This report describes a rare case of adult-onset type II citurullinemia that occurred in a patient who only had the heterozygote mutation, and had never presented with any symptoms before surgery. CASE PRESENTATION: A 56-year-old man underwent a total gastrectomy for stomach cancer. On postoperative Day 13, he suddenly developed presyncope, and blood tests showed hyperammonemia and high levels of serum citrulline. He was diagnosed with hepatic encephalopathy. DNA analysis revealed a heterozygote mutation in Solute Carrier Family 25. Although the patient received a conservative treatment, episodes of loss of consciousness and abnormality of behavior repeatedly occurred. CONCLUSION: Abdominal surgery involving the reconstruction of digestive tract alters the mechanisms of absorption and/or metabolism such that the symptoms of adult-onset type II citurullinemia may arise. Liver transplantation should be performed if all conservative treatments are unsuccessful.

10.
Case Rep Med ; 2015: 342148, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26167180

RESUMO

A 76-year-old Japanese man was referred to our hospital with chief complaint of right hypochondoralgia. Abdominal ultrasound showed a retroperitoneal tumor in the suprarenal region of the right kidney. Computed tomography revealed an enhanced lobular tumor with irregular, circumscribed, and indistinct border. Ultrasound-guided biopsy was performed. The tumor consisted of spindle-shaped cells with a giant nucleus and multinuclear cells. The diagnosis was leiomyosarcoma by immunohistochemical staining. The patient underwent surgery accessed by a right eighth intercostal thoracoabdominal incision. The tumor was completely resected, accompanied by removal of the posterosuperior segment of the right hepatic lobe, right adrenal gland, and a portion of the inferior vena cava (IVC). The histopathologic diagnosis was leiomyosarcoma arising from the IVC. We present a rare case of a successfully managed leiomyosarcoma of the IVC. This case suggests the importance of curative surgical resection of the tumor due to low efficacy of adjuvant chemotherapy for leiomyosarcoma.

11.
Case Rep Med ; 2015: 986971, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25688271

RESUMO

A 66-year-old Japanese man was referred to our hospital because of suspected duodenal cancer. Upper gastric endoscopy revealed a giant polypoid-type tumor that extended from the duodenum bulb to the pyloric ring. A computed tomography scan revealed a slightly enhanced lobular tumor protruding into the duodenum bulb. Positron emission tomography showed an accumulation of (18)F-fluorodeoxyglucose in the area extending from the antrum of the stomach to the duodenum bulb. Since an endoscopic ultrasound test suggested that the tumor might invade the muscular tunic, indications of endoscopic mucosal resection were not favored, and the tumor was curatively removed via distal gastrectomy. The histopathologic diagnosis was papillary adenocarcinoma, and the invasion depth was the mucosal layer without vascular invasion, which was different from the preoperative diagnosis. Our case suggests the difficulties in precise diagnosis of the invasion depth of the giant polypoid cancer.

12.
Dig Surg ; 31(4-5): 269-75, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25322745

RESUMO

AIMS: This study assessed the validity of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) score in maintenance hemodialysis patients undergoing elective abdominal surgery. METHODS: We retrospectively reviewed the medical records of 73 hemodialysis patients who underwent elective gastrointestinal surgery. The main outcomes analyzed were the E-PASS score and postoperative course, which were defined by mortality and morbidity. The discriminative capability of the E-PASS score was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The overall mortality rate observed was 2.7% (2 patients) and the morbidity rate was 36.9%. There were no significant differences in the comprehensive risk score, preoperative score or surgical stress score for patients with or without complications (p = 0.556, 0.639 and 0.168, respectively). Subsequent ROC curve analysis demonstrated poor predictive accuracy for morbidity. When the results in our study population were compared with those in Haga's study population, our population exhibited a highly significant rightward shift (p < 0.001). CONCLUSION: The E-PASS score was a poor predictor of complications because maintenance hemodialysis patients already have relatively high risk factors. This scoring system should not be applied in such a special group with high risk factors.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/psicologia , Procedimentos Cirúrgicos Eletivos/psicologia , Mortalidade Hospitalar , Diálise Renal/métodos , Estresse Fisiológico , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Estudos de Coortes , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/mortalidade , Feminino , Humanos , Japão , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Modelos Logísticos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Prognóstico , Testes Psicológicos , Curva ROC , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida , Resultado do Tratamento
13.
Gan To Kagaku Ryoho ; 40(5): 601-4, 2013 May.
Artigo em Japonês | MEDLINE | ID: mdl-23863581

RESUMO

The efficacy and safety of bevacizumab(BV), combined with infusional 5-fluorouracil/leucovorin(5-FU/LV)plus irinotecan(FOLFIRI)as the second-line treatment for metastatic colorectal cancer(mCRC)after resection of the primary lesion, have not been fully clarified. We examined clinical results of 35 patients on BV plus FOLFIRI at our hospital, and investigated the efficacy of BV plus FOLFIRI in mCRC patients who failed oxaliplatin-containing regimens(26 patients were treated with BV at a dose of 5mg/kg, 3 patients with BV 10mg/kg, and 6 patients had BV increased from 5mg/kg to 10mg/kg). The average frequency of BV plus FOLFIRI treatment was 13. 9 times, and the average length of treatment was 10. 0 months. The overall response rate was 17. 1%(CR 1 patient, PR 5 patients, SD 21 patients, PD 8 patients). The median PFS was 11. 0 months for FOLFIRI plus BV after first-line chemotherapy, and the median OS was 23. 0 months. The adverse events were 77. 1%(>Grade 3, 55. 5%)and the BV-associated adverse event was grade 3 hypertension(2 patients). The FOLFIRI plus BV regimen is an active and well-tolerated second-line chemotherapy treatment for patients with mCRC after resection of the primary lesion.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
14.
Surg Today ; 41(2): 297-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21264773

RESUMO

Management of patients undergoing dialysis after inguinal hernia surgery has not been standardized. This report presents the results of 9 patients with inguinal hernias (11 hernias) who were undergoing continuous ambulatory peritoneal dialysis (CAPD). All patients treated in this hospital since 2007 have returned to CAPD within 3 days after surgery without switching to hemodialysis (HD). The mean durations for resuming CAPD after surgery were 7.6 days from 1998 through 2007 and 2.3 days since 2008. The surgical procedure was performed with a polypropylene mesh in all cases. Local anesthesia was utilized for one patient with low cardiac function. All patients recovered rapidly, with no uremia or dialysis-related complications. No leakage or hernia recurrence was observed over the subsequent observation period (56.2 months). This experience suggests the possibility that interim HD can therefore be skipped in patients undergoing CAPD if the hernia sacs are closed tightly. Local anesthesia seems to be safe for high-risk hernia patients undergoing CAPD.


Assuntos
Hérnia Inguinal/cirurgia , Assistência Perioperatória/métodos , Diálise Peritoneal Ambulatorial Contínua , Adulto , Idoso , Anestesia Local , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polipropilenos , Telas Cirúrgicas , Fatores de Tempo
15.
Transplantation ; 85(6): 893-902, 2008 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-18360273

RESUMO

BACKGROUND: A regimen consisting of polyclonal anti-T-cell antibody, sirolimus (SRL), and donor bone marrow (DBM) infusion induces robust transplantation tolerance to skin allografts in mice. We investigated the effect of a similar regimen in a nonhuman primate (NHP) model. METHODS: Cynomolgus macaques (Macaca fascicularis) were transplanted with mismatched kidney allografts. Recipients were treated with 7 doses of antithymocyte globulin (Thymoglobulin, day 1 to 9), sirolimus, and DBM infusion (day 14). Anti-CD20 antibody, rituximab, was given on days 0 and 5. RESULTS: A regimen of Thymoglobulin, 30 days of SRL, and DBM infusion induced significantly greater prolongation of graft survival with a mean survival time of 88 days compared with the control regimen (no DBM) with an mean survival time of 53 days (P=0.022). Unlike the murine skin allograft model, all grafts were rejected within 111 days. A combination of Thymoglobulin, continuous SRL, and rituximab caused graft and systemic SV40 infection and failed to achieve further extension of graft survival. C4d deposition was observed in 50% of recipients as early as 18 days, suggesting antidonor antibody production. A transient, low-to-moderate degrees of multilineage chimerism was observed after DBM infusion. Treatment with Thymoglobulin resulted in profound depletion of CD4+ and CD8+ T cells, whereas addition of rituximab achieved prolonged (up to 3 months) depletion of CD20+ B cells. CONCLUSION: The Thymoglobulin, SRL, and DBM protocol is simple and produces long-term kidney allograft survival in NHP although additional treatment modalities may be necessary for induction of long-term tolerance.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Transplante de Rim/imunologia , Infecções por Polyomavirus/induzido quimicamente , Infecções Tumorais por Vírus/induzido quimicamente , Animais , Anticorpos Monoclonais Murinos , Linfócitos B/imunologia , Transplante de Medula Óssea , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Complemento C4b/análise , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Transplante de Rim/patologia , Contagem de Linfócitos , Macaca fascicularis , Fragmentos de Peptídeos/análise , Infecções por Polyomavirus/patologia , Rituximab , Vírus 40 dos Símios , Doadores de Tecidos , Transplante Homólogo , Infecções Tumorais por Vírus/patologia
16.
J Immunol ; 179(8): 5584-91, 2007 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-17911646

RESUMO

T cell depletion is a widely used approach in clinical transplantation. However, not all T cells are equally sensitive to depletion therapies and a significant fraction of T cells persists even after aggressive treatment. The functional attributes of such T cells and the mechanisms responsible for their resistance to depletion are poorly studied. In the present study, we showed that CD4(+) T cells that are resistant to polyclonal anti-lymphocyte serum (ALS) mediated depletion exhibit phenotypic features of memory cells and uniformly express OX40 on the cell surface. Studies using the foxp3gfp knockin mice revealed that the remaining CD4(+)OX40(+) cells consist of Foxp3(+) Tregs and Foxp3(-) T effector/memory cells. The ALS-resistant CD4(+)OX40(+) cells failed to mediate skin allograft rejection upon adoptive transferring into congenic Rag(-/-) mice, but removal of Foxp3(+) Tregs from the OX40(+) cells resulted in prompt skin allograft rejection. Importantly, OX40 is critical to survival of both Foxp3(+) Tregs and T effector/memory cells. However, OX40 exhibits opposing effects on the functional status of Foxp3(+) Tregs and T effector/memory cells, as stimulation of OX40 on T effector cells induced amplified cell proliferation but stimulation of OX40 on the Foxp3(+) Tregs impaired their suppressor functions. Our study demonstrates that OX40 is a critical molecule in regulating survival and functions of depletion-resistant T cells; and these findings may have important clinical implications.


Assuntos
Imunidade Inata , Depleção Linfocítica , Receptores OX40/fisiologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Animais , Soro Antilinfocitário/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/genética , Genes Reporter , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Imunidade Inata/genética , Imunofenotipagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Camundongos Transgênicos , Receptores OX40/biossíntese , Receptores OX40/deficiência , Receptores OX40/genética , Transplante de Pele/imunologia , Subpopulações de Linfócitos T/citologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
17.
Circulation ; 114(1 Suppl): I186-92, 2006 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-16823956

RESUMO

BACKGROUND: Cardioplegia and cardiopulmonary bypass (CP/CPB) leads to an increase in circulating progenitor cells. The role of stromal-derived factor-1alpha (SDF-1alpha), a key regulator of progenitor cell mobilization, and other cytokines in this process is not clear. METHODS AND RESULTS: Peripheral blood (n=24), atrial and skeletal tissue (n=6) samples were taken from patients undergoing CP/CPB before (pre-CP/CPB), 4 hours (post-CP/CPB), and 4 days (POD4) after CP/CPB. The number of circulating CD34+CXCR4+ cells increased post-CP/CPB (442+/-53 versus 286+/-27; P=0.04 versus pre-CP/CPB), but not at POD4 (382+/-50; P=0.28 versus pre-CP/CPB). Plasma levels of SDF-1alpha increased post-CP/CPB as compared with pre-CP/CPB (3325+/-325 versus 2911+/-165 pg/mL; P=0.046) but returned to baseline at POD4 (2838+/-224 pg/mL; P=0.90). Plasma levels of vascular endothelial growth factor were similar post-CP/CPB (P=0.90 versus pre-CP/CPB) but increased at POD4 (220+/-40 pg/mL versus 134+/-26 pg/mL; P=0.04 versus pre-CP/CPB). Serum levels of granulocyte-colony stimulating factor (G-CSF) increased early after CP/CPB as compared with pre-CP/CPB (265.0+/-41.7 versus 11.1+/-1.1 pg/mL; P<0.001) and returned to baseline at POD4 (P=0.84 versus pre-CP/CPB). The circulating CD34+CXCR4+ cells were positively correlated with plasma levels of SDF-1alpha early after CP/CPB (r=0.56, P<0.01), but not at other times. Protein expression of SDF-1alpha was elevated in the atrial myocardium after CP/CPB (9.4-fold; P=0.03). CONCLUSIONS: Exposure to CP/CPB leads to an increase in circulating CD34+CXCR4+ progenitor cells, which is associated with increased myocardial SDF-1alpha expression. The numbers of CD34+CXCR4+ progenitor cells positively correlate with the plasma levels of SDF-1alpha post-CP/CPB, suggesting an important role of SDF-1alpha in progenitor cell mobilization.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar/efeitos adversos , Quimiocinas CXC/fisiologia , Parada Cardíaca Induzida/efeitos adversos , Células-Tronco Hematopoéticas/fisiologia , Inflamação/fisiopatologia , Idoso , Antígenos CD34/análise , Quimiocina CXCL12 , Quimiocinas CXC/biossíntese , Quimiocinas CXC/sangue , Quimiocinas CXC/genética , Feminino , Regulação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos/sangue , Átrios do Coração/metabolismo , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Receptores CXCR4/análise , Fator A de Crescimento do Endotélio Vascular/sangue
18.
J Autoimmun ; 26(4): 225-31, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16713179

RESUMO

Treatment of overtly diabetic NOD mice with antilymphocyte serum (ALS), a polyclonal anti-T cell antibody, leads to cure of diabetes. Here, we investigated whether ALS-treatment of NOD mice after development of extensive insulitis prevents onset of diabetes. Female NOD mice were treated with two doses of ALS at 14, 19 or 23 weeks of age. No further treatment was given. In untreated female NOD mice, diabetes developed starting at 13 weeks and reached 68% by 37 weeks. ALS-treatment at 14, 19 or 23 weeks when histology showed progressive insulitis completely prevented onset of overt diabetes in 9/12, 11/12 or 12/12 mice, respectively. Intraperitoneal glucose tolerance tests in 43 week-old ALS-treated, diabetes-free mice showed a normal pattern. Co-adoptive transfer of lymphoid cells prepared from ALS-treated diabetes-free mice together with splenocytes from overtly diabetic NOD mice resulted in marked delay in diabetes onset in NOD.SCID mice, suggesting the presence of autoimmune regulatory cells in ALS-treated mice. Autoimmune regulatory cells were CD4(+)CD25(+), but not CD4(+)CD25(-), T cells. Thus, treatment of euglycemic individuals who already show signs of autoimmune diabetes with a short course of polyclonal anti-T cell antibody may effectively prevent onset of type 1 diabetes mellitus.


Assuntos
Soro Antilinfocitário/farmacologia , Diabetes Mellitus Tipo 1/prevenção & controle , Ilhotas Pancreáticas/patologia , Animais , Soro Antilinfocitário/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Teste de Tolerância a Glucose , Ilhotas Pancreáticas/imunologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Endogâmicos NOD , Camundongos SCID , Coelhos , Linfócitos T/imunologia
19.
J Immunol ; 176(7): 4125-32, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16547248

RESUMO

Broad T cell depletion has been used as an integral part of treatment in transplantation and autoimmune diseases. Following depletion, residual T cells undergo homeostatic proliferation and convert to memory-like T cells. In this study, we investigated the effect of T cell depletion by antilymphocyte serum (ALS), a polyclonal anti-T cell Ab, on CD4(+) regulatory T cells. After ALS treatment, CD4(+)CD25(+) T cells underwent proliferation and expressed a memory T cell marker, CD44. One week after ALS treatment, both CD25(+) and CD25(-) T cells exhibited increased suppression of alloresponses in vitro, which waned thereafter to the levels mediated by naive CD25(+) and CD25(-) T cells. By real-time PCR analyses, ALS treatment of CD4-deficient mice adoptively transferred with Thy1.2(+)CD4(+)CD25(+)Foxp3(+) and Thy1.1(+)CD4(+)CD25(-)Foxp3(-) T cells resulted in the appearance of Thy1.2(+)CD4(+)CD25(-)Foxp3(+) and Thy1.1(+)CD4(+)CD25(+)Foxp3(+) T cells, suggesting the conversion between CD25(+) and CD25(-) T cells. Naive CD25(+) T cells expressed a higher level of intracellular Bcl-x(L) than CD25(-) T cells. Up-regulation of the Bcl-x(L) molecule during ALS-induced homeostatic expansion further promoted survival of CD25(+) and, to a lessor degree, CD25(-) cells. These results indicate that CD25(+) T cells are spared from ALS-mediated deletion, with some CD25(+) T cells converting to CD25(-) T cells, and continue to exhibit regulatory activity. The concomitant presence of T cell deletion and continuous regulatory T cell activity may underlie the therapeutic effect of ALS, particularly in treatment of autoimmune diseases.


Assuntos
Anticorpos/imunologia , Soro Antilinfocitário/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Animais , Biomarcadores , Linfócitos T CD4-Positivos/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica/imunologia , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Receptores de Interleucina-2/metabolismo , Proteína bcl-X/metabolismo
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