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1.
Gan To Kagaku Ryoho ; 50(13): 1683-1684, 2023 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-38303172

RESUMO

We present a case of oligo lymph node metastasis in a 70s man who had previously undergone subtotal gastrectomy for advanced gastric cancer in the prepylorus. Postoperatively, adjuvant chemotherapy was administered for a duration of 1 year. During the third postoperative year, elevated tumor markers and lymph node enlargement prompted a diagnosis of lymph node metastasis. Subsequent chemoradiotherapy resulted in a complete response(CR), which has been sustained for 2 years without any recurrence. The outcomes of this case indicate that chemoradiotherapy stands as a viable treatment option for oligo lymphatic recurrence in gastric cancer.


Assuntos
Linfadenopatia , Neoplasias Gástricas , Humanos , Masculino , Quimiorradioterapia , Quimioterapia Adjuvante , Gastrectomia , Excisão de Linfonodo , Linfonodos/cirurgia , Linfonodos/patologia , Metástase Linfática , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Idoso
2.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34548395

RESUMO

Extracellular adenosine triphosphate (ATP) released by mucosal immune cells and by microbiota in the intestinal lumen elicits diverse immune responses that mediate the intestinal homeostasis via P2 purinergic receptors, while overactivation of ATP signaling leads to mucosal immune system disruption, which leads to pathogenesis of intestinal inflammation. In the small intestine, hydrolysis of luminal ATP by ectonucleoside triphosphate diphosphohydrolase (E-NTPD)7 in epithelial cells is essential for control of the number of T helper 17 (Th17) cells. However, the molecular mechanism by which microbiota-derived ATP in the colon is regulated remains poorly understood. Here, we show that E-NTPD8 is highly expressed in large-intestinal epithelial cells and hydrolyzes microbiota-derived luminal ATP. Compared with wild-type mice, Entpd8-/- mice develop more severe dextran sodium sulfate-induced colitis, which can be ameliorated by either the depletion of neutrophils and monocytes by injecting with anti-Gr-1 antibody or the introduction of P2rx4 deficiency into hematopoietic cells. An increased level of luminal ATP in the colon of Entpd8-/- mice promotes glycolysis in neutrophils through P2x4 receptor-dependent Ca2+ influx, which is linked to prolonged survival and elevated reactive oxygen species production in these cells. Thus, E-NTPD8 limits intestinal inflammation by controlling metabolic alteration toward glycolysis via the P2X4 receptor in myeloid cells.


Assuntos
Adenosina Trifosfatases/fisiologia , Trifosfato de Adenosina/metabolismo , Colite/prevenção & controle , Glicólise , Células Mieloides/metabolismo , Receptores Purinérgicos P2X4/metabolismo , Células Th17/imunologia , Animais , Células Cultivadas , Colite/etiologia , Colite/metabolismo , Colite/patologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides/imunologia , Células Mieloides/patologia , Receptores Purinérgicos P2X4/genética , Transdução de Sinais
3.
Surg Laparosc Endosc Percutan Tech ; 29(3): 200-202, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30640819

RESUMO

AIM: To evaluate the efficacy of single-incision laparoscopic surgery for totally extraperitoneal repair in overweight or obese patients. MATERIALS AND METHODS: For outcome analyses, patients were subdivided by body mass index (BMI) as normal-weight (18.5≤BMI<25 kg/m), overweight (25≤BMI<30 kg/m) or obese (≥30 kg/m) and compared. RESULTS: In total, 201 patients were divided into a normal-weight group (n=152) and an overweight/obese group (n=49). Median operative time for unilateral hernia was 72 minutes in the normal-weight group and 95 minutes in the overweight/obese group (P<0.05). No significant differences in operative time for bilateral hernia, bleeding volume, peritoneal injury, conversion to a different procedure, postoperative hospital stay, follow-up duration, complications, or recurrence were identified. CONCLUSIONS: Single-incision laparoscopic surgery for totally extraperitoneal repair, which offers good cosmetic outcomes, seems feasible and safe for overweight or obese patients, although the operation takes longer.


Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Laparoscopia/métodos , Sobrepeso/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Duração da Cirurgia , Peritônio/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
4.
Asian J Endosc Surg ; 12(3): 301-305, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30133152

RESUMO

INTRODUCTION: The learning curve for totally extraperitoneal repair (TEP) is longer and steeper than that for transabdominal preperitoneal repair (TAPP) due to the preperitoneal view to which the surgeon is not accustomed and the limited working space. The aim of this study was to clarify the learning curve for SILS-TEP. METHODS: A retrospective analysis of 80 consecutive patients with unilateral inguinal hernia was performed. All patients underwent elective SILS-TEP performed by a single learning surgeon with a teaching assistant between July 2016 and March 2018 at Kinki Central Hospital. RESULTS: The operative time decreased gradually after 20 cases and stabilized after 40 cases. The first 40 cases were categorized as the learning period group, and the remaining 40 cases were categorized as the experienced period group. More patients received antithrombotic therapy in the experienced period than in the learning period (P < 0.05). The median operative time was 107 and 60 min in the learning period and the experienced period, respectively (P < 0.05). There were no significant differences in blood loss peritoneal injury, conversion to a different procedure, postoperative hospital stay, complications, and recurrence between the two groups. No major complications or hernia recurrence were noted during follow-up. CONCLUSIONS: The learning curve for SILS-TEP might take 40 cases to reduce the operative time. SILS-TEP can be performed safely by a learning surgeon with a teaching assistant.


Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/educação , Laparoscopia/educação , Curva de Aprendizado , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Herniorrafia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
5.
Gan To Kagaku Ryoho ; 46(13): 2231-2233, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-32156888

RESUMO

The patient was a 60-year-old man who underwent distal gastrectomy for gastric cancer. The pathological diagnosis was Stage ⅡB. He received adjuvant chemotherapy(capecitabine plus oxaliplatin: CapeOX)for 6months and the postoperative course was uneventful. One year and 3 months after surgery, he visited the outpatient department for acute lower back pain. Blood tests showed elevated ALP(3,752 U/L), LDH(308 U/L), and CA19-9(69.4 U/mL)levels. Bone scintigraphy showed multiple bone metastases to the femora, ischium, iliac bone, vertebrae, sternum, costae, and scapulae in a super bone scan. The onset of disseminated intravascular coagulation(DIC)was observed later. The patient was diagnosed with disseminated carcinomatosis of the bone marrow. Radiation therapy was performed and anti-RANKL monoclonal antibody was administered for the bone metastases. Recombinant human soluble thrombomodulin was administered for DIC. He received chemotherapy( TS-1 plus cisplatin: SP)but died 4 months after the diagnosis. The prognosis of disseminated carcinomatosis of the bone marrow is extremely poor. We report this case along with a literature review.


Assuntos
Neoplasias da Medula Óssea , Coagulação Intravascular Disseminada , Neoplasias Peritoneais , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica , Medula Óssea , Neoplasias da Medula Óssea/secundário , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgia
6.
Ann Med Surg (Lond) ; 34: 54-57, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30224949

RESUMO

INTRODUCTION: Repair of supra-pubic incisional hernia is still challenging because of the highest pressure at the lower abdominal wall in the erect position. Recently, laparoscopic preperitoneal mesh repair has been gradually reported. CASE PRESENTATION: A 77-year-old woman underwent single-incision laparoscopic preperitoneal mesh repair under a diagnosis of a supra-pubic incisional hernia, measuring 7 × 4 cm. A single, 2.5-cm, intraumbilical incision was made, followed by creation of the preperitoneal space. Then, the posterior rectus sheath and peritoneum were opened, and laparoscopic exploration was performed. After dissection of the supra-pubic hernia content, the tube for degassing the abdominal cavity was inserted into the abdominal cavity, and the peritoneum and the posterior sheath were closed. The preperitoneal space was dissected gradually, and circular dissection of the hernia sac was performed. The proximal sac (peritoneum) was sutured continuously. A 15 × 10 cm mesh was placed in the preperitoneal space and fixed securely with absorbable tacks at the pubic bone, Cooper's ligament, and the rectus abdominis muscle, respectively. After degassing the preperitoneal space, a second laparoscopic exploration was performed to confirm the secure suture of the peritoneum and no injury of the abdominal organs. At 4-month follow-up, the patient remained well with no signs of recurrence. DISCUSSION: Single-incision laparoscopic preperitoneal mesh repair could minimize the recurrence of supra-umbilical incisional hernia and perioperative complications. CONCLUSION: Single-incision laparoscopic preperitoneal mesh repair, offering good cosmetic results, might be useful for repair of supra-pubic incisional hernia.

7.
Thorac Cancer ; 9(4): 466-471, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29473311

RESUMO

BACKGROUND: Activating EGFR mutations, HER2, and HER3 are implicated in lung cancer; however, with the exception of EGFR gene amplification in lung adenocarcinoma harboring EGFR mutations, their involvement in disease progression during the early stages is poorly understood. In this paper, we focused on which receptor is correlated with lung adenocarcinoma progression in the presence or absence of EGFR mutation from stage 0 to IA1. METHODS: HER2 and HER3 expression and activating EGFR mutations in surgically resected lung adenocarcinoma exhibiting ground glass nodules on chest computed tomography and re-classified to stage 0 and IA1 were examined by immunohistochemistry and peptide nucleic acid-locked nucleic acid PCR clamp method, respectively. RESULTS: HER2 and HER3 expression was detected in 22.2% and 86.1% of samples, respectively. The frequency of EGFR mutation was 45.7% and was not significantly different between stage 0 and IA1 (40.0% and 48.0%, respectively), suggesting that EGFR mutation does not correlate with cancer progression from stage 0 to IA1. HER2 expression also did not correlate to progression. However, not only the frequency, but also the intensity of HER3 expression was increased in stage IA1 lung adenocarcinoma, particularly in lung adenocarcinoma without EGFR mutation. CONCLUSION: HER3 tends to be intensively expressed during the progression of lung adenocarcinoma without EGFR mutation from carcinoma in situ to invasive carcinoma.


Assuntos
Adenocarcinoma de Pulmão/genética , Receptor ErbB-2/genética , Receptor ErbB-3/genética , Adenocarcinoma de Pulmão/classificação , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Progressão da Doença , Receptores ErbB/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X
8.
Surg Today ; 48(4): 380-387, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28993901

RESUMO

PURPOSE: We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. METHODS: Patients with resectable c-stage IB-IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. RESULTS: Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CONCLUSIONS: CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain.


Assuntos
Carboplatina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Colágeno , Meios de Cultura , Técnicas de Cultura/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Paclitaxel/farmacologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimioterapia Combinada , Feminino , Géis , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Medicina de Precisão , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Asian Cardiovasc Thorac Ann ; 25(1): 41-46, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27899430

RESUMO

Background To prevent postoperative middle lobe torsion after a right upper lobectomy, we introduced a novel technique of interlobar fixation using collagen fleece coated with fibrin. In this study, the prophylactic effects of this method on the incidence of postoperative pulmonary torsion were analyzed. Methods Between April 2001 and December 2015, 3786 pulmonary resection procedures (excluding total pneumonectomy) were performed in our institution, and prophylactic interlobar fixation was selectively applied when intraoperative examination indicated that the patient was at high risk of postoperative pulmonary lobe torsion. As a control group, 842 patients who underwent pulmonary resection procedures between January 1996 and April 2001 were reviewed. Results During the study period, 10 (0.3%) patients underwent prophylactic middle lobe fixation (to the lower lobe after a right upper lobectomy in 9, and to the upper lobe after a right lower lobectomy in one). Pulmonary lobar (middle lobe) torsion occurred in only one patient (after right upper lobectomy); thus the incidence of this complication was 0.1% among patients who underwent a right upper lobectomy and 0.03% among all pulmonary resection procedures. The rates during the study period were marginally significantly lower than those in the control period (1.3% and 0.24%, respectively; p = 0.071 and p = 0.087, respectively). Conclusion Prophylactic middle lobe fixation might be useful for preventing postoperative pulmonary middle lobe torsion.


Assuntos
Aprotinina/uso terapêutico , Fibrinogênio/uso terapêutico , Pneumopatias/prevenção & controle , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Trombina/uso terapêutico , Anormalidade Torcional/prevenção & controle , Idoso , Combinação de Medicamentos , Feminino , Humanos , Pneumopatias/diagnóstico , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Anormalidade Torcional/diagnóstico , Anormalidade Torcional/etiologia , Resultado do Tratamento
10.
Nature ; 532(7597): 117-21, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27027293

RESUMO

Colonic epithelial cells are covered by thick inner and outer mucus layers. The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis. In the small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified. Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8(-/-) mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8(-/-) mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.


Assuntos
Colo/microbiologia , Epitélio/microbiologia , Flagelos , Proteínas Ligadas por GPI/metabolismo , Bactérias Gram-Negativas/fisiologia , Mucosa Intestinal/microbiologia , Animais , Aderência Bacteriana , Células CACO-2 , Linhagem Celular , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Sulfato de Dextrana , Feminino , Proteínas Ligadas por GPI/deficiência , Proteínas Ligadas por GPI/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Negativas/patogenicidade , Homeostase , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/genética , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/metabolismo , Proteus mirabilis/patogenicidade , Simbiose
11.
Immunity ; 42(2): 279-293, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25692702

RESUMO

Crosslinking of the immunoglobulin receptor FcεRI activates basophils and mast cells to induce immediate and chronic allergic inflammation. However, it remains unclear how the chronic allergic inflammation is regulated. Here, we showed that ecto-nucleotide pyrophosphatase-phosphodiesterase 3 (E-NPP3), also known as CD203c, rapidly induced by FcεRI crosslinking, negatively regulated chronic allergic inflammation. Basophil and mast cell numbers increased in Enpp3(-/-) mice with augmented serum ATP concentrations. Enpp3(-/-) mice were highly sensitive to chronic allergic pathologies, which was reduced by ATP blockade. FcεRI crosslinking induced ATP secretion from basophils and mast cells, and ATP activated both cells. ATP clearance was impaired in Enpp3(-/-) cells. Enpp3(-/-)P2rx7(-/-) mice showed decreased responses to FcεRI crosslinking. Thus, ATP released by FcεRI crosslinking stimulates basophils and mast cells for further activation causing allergic inflammation. E-NPP3 decreases ATP concentration and suppresses basophil and mast cell activity.


Assuntos
Trifosfato de Adenosina/metabolismo , Asma/imunologia , Basófilos/imunologia , Mastócitos/imunologia , Diester Fosfórico Hidrolases/imunologia , Pirofosfatases/imunologia , Receptores de IgE/imunologia , Trifosfato de Adenosina/farmacologia , Animais , Basófilos/citologia , Dermatite de Contato/imunologia , Diarreia/imunologia , Diarreia/patologia , Imunoglobulina E/imunologia , Mastócitos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Anafilaxia Cutânea Passiva/imunologia , Diester Fosfórico Hidrolases/genética , Pirofosfatases/genética , Interferência de RNA , RNA Interferente Pequeno , Receptores Purinérgicos P2X7/genética , Receptores Purinérgicos P2X7/imunologia , Trinitrobenzenos/imunologia
12.
J Immunol ; 190(2): 774-83, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23241884

RESUMO

Extracellular ATP is released from live cells in controlled conditions, as well as dying cells in inflammatory conditions, and, thereby, regulates T cell responses, including Th17 cell induction. The level of extracellular ATP is closely regulated by ATP hydrolyzing enzymes, such as ecto-nucleoside triphosphate diphosphohydrolases (ENTPDases). ENTPDase1/CD39, which is expressed in immune cells, was shown to regulate immune responses by downregulating the ATP level. In this study, we analyzed the immunomodulatory function of ENTPDase7, which is preferentially expressed in epithelial cells in the small intestine. The targeted deletion of Entpd7 encoding ENTPDase7 in mice resulted in increased ATP levels in the small intestinal lumen. The number of Th17 cells was selectively increased in the small intestinal lamina propria in Entpd7(-/-) mice. Th17 cells were decreased by oral administration of antibiotics or the ATP antagonist in Entpd7(-/-) mice, indicating that commensal microbiota-dependent ATP release mediates the enhanced Th17 cell development in the small intestinal lamina propria of Entpd7(-/-) mice. In accordance with the increased number of small intestinal Th17 cells, Entpd7(-/-) mice were resistant to oral infection with Citrobacter rodentium. Entpd7(-/-) mice suffered from severe experimental autoimmune encephalomyelitis, which was associated with increased numbers of CD4(+) T cells producing both IL-17 and IFN-γ. Taken together, these findings demonstrate that ENTPDase7 controls the luminal ATP level and, thereby, regulates Th17 cell development in the small intestine.


Assuntos
Trifosfato de Adenosina/metabolismo , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Pirofosfatases/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Animais , Citrobacter rodentium/imunologia , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/imunologia , Feminino , Regulação da Expressão Gênica , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Intestino Delgado/microbiologia , Metagenoma , Camundongos , Camundongos Knockout , Pirofosfatases/genética
13.
J Immunol ; 189(6): 2869-78, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22869901

RESUMO

Dietary compounds as well as commensal microbiota contribute to the generation of a unique gut environment. In this study, we report that dietary folic acid (FA) is required for the maintenance of Foxp3+ regulatory T cells (Tregs) in the colon. Deficiency of FA in the diet resulted in marked reduction of Foxp3+ Tregs selectively in the colon. Blockade of folate receptor 4 and treatment with methotrexate, which inhibits folate metabolic pathways, decreased colonic Foxp3+ Tregs. Compared with splenic Tregs, colonic Tregs were more activated to proliferate vigorously and were highly sensitive to apoptosis. In colonic Tregs derived from mice fed with a FA-deficient diet, expression of anti-apoptotic molecules Bcl-2 and Bcl-xL was severely decreased. A general reduction of peripheral Tregs was induced by a neutralizing Ab against IL-2, but a further decrease by additional FA deficiency was observed exclusively in the colon. Mice fed with an FA-deficient diet exhibited higher susceptibility to intestinal inflammation. These findings reveal the previously unappreciated role of dietary FA in promotion of survival of Foxp3+ Tregs that are in a highly activated state in the colon.


Assuntos
Ração Animal , Colo/imunologia , Colo/metabolismo , Ácido Fólico/administração & dosagem , Ácido Fólico/fisiologia , Fatores de Transcrição Forkhead/biossíntese , Linfócitos T Reguladores/imunologia , Animais , Sobrevivência Celular/imunologia , Colo/citologia , Fatores de Transcrição Forkhead/fisiologia , Técnicas de Introdução de Genes , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/fisiologia
14.
PLoS Pathog ; 8(5): e1002714, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22693446

RESUMO

Specific intestinal microbiota has been shown to induce Foxp3(+) regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103(+) dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103(+) DCs from Il10(-/-), Tlr2(-/-), and Myd88(-/-) mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103(+) DCs failed to induce IL-10 production from co-cultured Il27ra(-/-) T cells. B. breve treatment of Tlr2(-/-) mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103(+) DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4(+) T cells from wild-type mice, but not Il10(-/-) mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.


Assuntos
Bifidobacterium/imunologia , Colo/microbiologia , Interleucina-10/metabolismo , Lacticaseibacillus casei/imunologia , Probióticos/administração & dosagem , Linfócitos T Reguladores/citologia , Transferência Adotiva , Animais , Infecções por Bifidobacteriales/imunologia , Infecções por Bifidobacteriales/microbiologia , Infecções por Bifidobacteriales/terapia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/transplante , Diferenciação Celular , Técnicas de Cocultura , Colite/imunologia , Colite/microbiologia , Colite/terapia , Colo/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Interações Hospedeiro-Patógeno , Hospedeiro Imunocomprometido , Interleucina-10/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
15.
Gen Thorac Cardiovasc Surg ; 60(7): 452-5, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22544422

RESUMO

A 44-year-old woman, who had been diagnosed as having null type alpha-1 antitrypsin (AAT) deficiency, was admitted with right recurrent pneumothorax. She had undergone right visceral pleural strengthening and pleural adhesion-preventing surgery, the total pleural covering technique (TPC), with oxidized regenerative cellulose (ORC). Three years after the operation, she developed left recurrent pneumothorax and underwent left TPC. AAT deficiency is a rare inherited disease in Japan that causes early-onset emphysema and secondary pneumothorax. In addition, null/null phenotype has the highest risk of emphysema and may require lung transplantation. For future lung transplantation, pleural adhesion should be prevented. However, pleurodesis and surgery for pneumothorax generally cause adhesion. TPC with ORC is a surgical treatment for pneumothorax that is done to strengthen visceral pleura and prevent pleural adhesions. The patient has had no recurrence of pneumothorax 3.5 years after right TPC and 6 months after left TPC.


Assuntos
Pneumotórax/cirurgia , Cirurgia Torácica Vídeoassistida , Deficiência de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/genética , Adulto , Celulose Oxidada , Desenho de Equipamento , Feminino , Predisposição Genética para Doença , Humanos , Fenótipo , Doenças Pleurais/etiologia , Doenças Pleurais/prevenção & controle , Pneumotórax/diagnóstico , Pneumotórax/etiologia , Recidiva , Telas Cirúrgicas , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/instrumentação , Aderências Teciduais , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/diagnóstico
16.
Int Immunol ; 22(12): 953-62, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21051439

RESUMO

Several subsets of innate immune cells, all with unique properties, reside within the intestinal lamina propria. However, compared with intestinal dendritic cells (DCs), intestinal macrophages are less well characterized. In this study, we examined the properties of macrophages in the colonic lamina propria (LMφ). Colonic DCs (LDC) showed LPS-induced production of IL-12p40. In contrast, LMφ showed constitutive IL-10 production and unresponsiveness to LPS in terms of inflammatory cytokine production. Comparison of the gene expression profiles between LMφ and LDC revealed that LMφ preferentially expressed IL-10-related genes. LMφ obtained from mice lacking IL-10 or Stat3 showed hyperproduction of tumour necrosis factor (TNF)-α and IL-6 in response to LPS. IL-10 production in the large intestine was mainly induced by LMφ and regulatory T cells and was dependent on the presence of commensal microbiota. Accordingly, LMφ from germ-free mice showed less production of IL-10 and increased levels of LPS-induced TNF-α and IL-6 production. Taken together, these results demonstrate that the activity of LMφ to produce pro-inflammatory cytokines is negatively regulated through commensal microbiota-dependent IL-10 production in the large intestine.


Assuntos
Colo/imunologia , Interleucina-10/biossíntese , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Metagenoma/imunologia , Animais , Antígeno CD11b/biossíntese , Antígeno CD11c/genética , Colo/microbiologia , Células Dendríticas/imunologia , Deleção de Genes , Imunidade Inata , Interleucina-6/biossíntese , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucosa/imunologia , Mucosa/microbiologia , Fator de Necrose Tumoral alfa/biossíntese
17.
Surg Today ; 40(2): 102-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20107947

RESUMO

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies to the striated muscle tissue. It is often treated by thymectomy. We review recent studies to investigate the biological implications of thymectomy. In anti-acetylcholine receptor antibody (anti-AchR Ab)-positive patients without a thymoma, abnormal germinal center formation in the thymus seems to play an essential role in the pathogenesis of MG. Specific differentiation of B cells producing anti-AchR Ab takes place uniquely in the thymus, and thymectomy is thought to assist in terminating the provision of high-affinity anti-AchR antibody-producing cells to peripheral organs. Thymectomy is not indicated for anti-AchR Ab-negative MG patients who are antimuscle specific kinase antibody (anti-MuSK Ab)-positive, although some anti-MuSK Ab-negative patients may benefit from the procedure. A thymoma can be considered as an acquired thymus with insufficient function of negative selection. The resection of a thymoma is thought to terminate the production of self-reactive T cells. Thus, the biological implications of thymectomy for MG have been partially revealed. Nevertheless, additional studies are needed to elucidate the ontogeny of T cells that recognize AchR and the mechanism of the activation of anti-AchR antibodies producing B cells.


Assuntos
Miastenia Gravis/imunologia , Miastenia Gravis/cirurgia , Receptores Nicotínicos/imunologia , Linfócitos T/imunologia , Timectomia , Timoma/imunologia , Adulto , Fatores Etários , Autoanticorpos , Linfócitos B/imunologia , Ciclosporina/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Receptores Proteína Tirosina Quinases , Receptores Colinérgicos , Tacrolimo/uso terapêutico , Timoma/cirurgia , Timo/imunologia
18.
Asian Cardiovasc Thorac Ann ; 16(5): 387-91, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18812347

RESUMO

Controversy exists regarding the clinical characteristics, pathological findings, and prognosis of patients < 50 years of age with primary lung cancer. The medical records of 4,556 patients diagnosed with primary lung cancer between 1980 and 2004 were reviewed; of these, 305 were < 50 years old. Of 1,335 patients who were surgically treated, 122 were < 50 years old. Females were over-represented in the younger group. Younger patients had a significantly higher incidence of adenocarcinoma and large cell carcinoma, and a lower incidence of squamous cell carcinoma. The resectable rate in younger patients was significantly higher. Overall and among surgically treated patients, the survival rates of younger patients with stage 0-I disease were significantly better than those of older patients. Younger patients with early-stage primary lung cancer had a significantly better prognosis than older patients, although survival in the advanced stages was not significantly different.


Assuntos
Adenocarcinoma , Carcinoma de Células Grandes , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Pneumonectomia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Fatores Etários , Idoso , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
19.
Interact Cardiovasc Thorac Surg ; 6(4): 484-9, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17669912

RESUMO

We reviewed the records of 12 patients with primary tracheobronchial tumors and various clinical characteristics treated at our institution to investigate our overall management experience with disease. Over a 21-year period, we treated 1405 cases of primary pulmonary neoplasms, of which 12 (0.9%) patients had primary tracheobronchial tumors with eight different histological types, including three adenoid cystic carcinomas, two bronchial carcinoids, two papillomas, one squamous cell carcinoma, one mucous gland adenoma, one inflammatory pseudotumor, one schwannoma, and one mucoepidermoid carcinoma. Eleven of the patients had symptoms of airway obstruction and/or secondary infection or bleeding. A complete resection was performed in ten, which included a sleeve lobectomy in seven, sleeve pneumonectomy in one, tracheal resection in one, and left main stem resection without lung resection in one. Median survival following complete resection was 91 months. When possible, a complete resection provides the best potential benefits and symptomatic relief for patients with tracheo-endobronchial tumors. Further, various options related to tracheobronchoplasty including conservative resection can be applied for surgical intervention.


Assuntos
Neoplasias Brônquicas/cirurgia , Neoplasias Pulmonares/cirurgia , Neoplasias da Traqueia/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Brônquicas/diagnóstico , Neoplasias Brônquicas/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Traqueia/diagnóstico , Neoplasias da Traqueia/patologia
20.
Jpn J Thorac Cardiovasc Surg ; 54(5): 187-92, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16764306

RESUMO

OBJECTIVES: We conducted a retrospective study of the clinical impact of a concomitant diagnostic and therapeutic procedure for patients with histologically unproven pulmonary nodules. METHODS: Between January 2001 and December 2003, we performed 150 consecutive surgical biopsy procedures for histologically indeterminate pulmonary nodules. We compared the clinical impact of the concomitant diagnostic wedge resection followed by lobectomy (U group, n=50) with that of a scheduled standard lobectomy in those with preoperatively proven clinical stage I lung cancer during the same period (C group, n=60). RESULTS: There were no significant differences in dichotomous variables, whereas we found significant differences in tumor size, operative time and blood loss between the 2 groups. Complication developed in 9 in the U group and 3 in the C group (p=0.030). Hospital mortality was 2% in the U group and 0% in the C group (p=0.11). CONCLUSION: Morbidity and mortality following a concomitant diagnostic and therapeutic procedure in patients with preoperatively undiagnosed lung cancer was acceptable, however, staged operations should be indicated for patients with considerable co-morbidity.


Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Técnicas de Diagnóstico por Cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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