RESUMO
BACKGROUND: Synchronous occurrence of intraductal papillary mucinous neoplasm (IPMN) and ductal carcinoma of the pancreas has been reported. Branch duct IPMNs with lower likelihood of malignancy are not submitted to resection but are followed-up, so ductal carcinoma may develop during the follow-up. The development of ductal carcinoma of the pancreas during follow-up of branch duct IPMNs was investigated. METHODS: 60 patients with branch duct IPMN who had an intraductal tumour of <10 mm on imaging examinations and a negative result for malignancy on cytological examination of the pancreatic juice were investigated. They were followed-up mainly by ultrasonography (US), and additionally by endoscopic ultrasonography (EUS), CT, magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) with cytological examination of the pancreatic juice for an average period of 87 months. RESULTS: Ductal carcinoma of the pancreas distinct from IPMN developed in 5 of 60 (8%) branch duct IPMNs during follow-up. The 5-year rate of development of ductal carcinoma was 6.9% (95% CI 0.4% to 13.4%), the incidence of ductal carcinoma was 1.1% (95% CI 0.1% to 2.2%) per year and the standardised incidence ratio of development of ductal carcinoma was 26 (95% CI 3 to 48). Patients >70 years old developed ductal carcinoma significantly more frequently than those under 69. Four of five ductal carcinomas identified during follow-up were resectable. Cancer developed in IPMN in 2 of 60 (3%) branch duct IPMNs during follow-up. CONCLUSIONS: During follow-up of branch duct IPMNs, ductal carcinoma of the pancreas not infrequently developed distinct from IPMN. In the follow-up of IPMN, special attention should be paid to the development of ductal carcinoma of the pancreas.
Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Papilar/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Papilar/diagnóstico , Idoso , Carcinoma Ductal Pancreático/diagnóstico , Progressão da Doença , Endossonografia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Fatores de TempoRESUMO
OBJECTIVE: To elucidate the role of macrophages in the pathogenesis of inflammatory bowel disease, proinflammatory characteristics of macrophages were estimated in a murine model of spontaneous intestinal inflammation. MATERIALS AND METHODS: Peritoneal macrophages from IL-10deficient mice were stimulated with lipopolysaccharide (LPS) or an anti-CD40 monoclonal antibody (mAb). Cytokine release was assessed by enzyme-linked immunosorbent assay. CD40 expression was examined by two-color flow cytometric analysis. Induction of suppressor of cytokine signaling 3 (SOCS3) mRNA was evaluated by real-time quantitative RT-PCR. RESULTS: In the presence of LPS or anti-CD40 mAb, TNF-alpha and IL-12p70 release from macrophages of mutant mice was significantly higher than that from macrophages of wild-type mice. This may be due to the difference in IL-10 production by macrophages, since activated macrophages of wild-type mice produced IL-10 in amounts sufficient to suppress an increased release of cytokines from activated macrophages of mutant mice. LPS and CD40 stimulation induced significantly high level of SOCS3 expression in macrophages of mutant mice in comparison to those of wild-type mice. CONCLUSIONS: Macrophages from a murine model of inflammatory bowel disease demonstrated enhanced responsiveness to immunological and bacterial stimuli. This suggests significant roles of macrophages in the pathogenesis of inflammatory bowel disease.
Assuntos
Antígenos CD40/imunologia , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Interleucina-10/deficiência , Lipopolissacarídeos/imunologia , Macrófagos Peritoneais/imunologia , Proteínas Repressoras , Fatores de Transcrição , Animais , Antígenos CD40/metabolismo , Citocinas/biossíntese , Regulação da Expressão Gênica , Inflamação/imunologia , Interleucina-10/biossíntese , Interleucina-10/genética , Interleucina-10/metabolismo , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de CitocinaRESUMO
Peroxisome proliferator-activated receptor gamma (PPARgamma) inhibits the growth of several types of cancer cells. However, the mechanisms by which this occurs are poorly understood. The goal of the present study was to investigate the effects of PPARgamma on mutated ras-induced cell growth, activation of transcription factors and expression of genes associated with cellular transformation in rat intestinal epithelial cells. A human PPARgamma cDNA was introduced to the activated H-ras-transfected IEC-6 cells (IECras) and 1 clone (IECrasPR82) that stably expresses both activated ras and PPARgamma was obtained. Thiazolidinedione derivatives such as troglitazone and rosiglitazone, selective ligands for PPARgamma, inhibited the cellular growth of IECrasPR82 cells in a time-dependent manner and induced G1 cell cycle arrest. Treatment with troglitazone (20 microM) decreased the expression of cyclin D1, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and amphiregulin and suppressed the promoter activities of cyclin D1 and HB-EGF. Furthermore, a luciferase assay and an electrophoretic mobility shift assay showed that thiazolidinedione derivatives suppressed the transcriptional activities of AP-1 and Ets, both of which play crucial roles in the expression of cyclin D1 and HB-EGF. These findings suggest that reduction of EGF-like growth factors and cyclin D1 through the suppression of AP-1 and Ets may be 1 mechanism whereby PPARgamma inhibits their growth.
Assuntos
Ciclina D1/biossíntese , Fator de Crescimento Epidérmico/biossíntese , Receptores Citoplasmáticos e Nucleares/agonistas , Tiazolidinedionas , Fatores de Transcrição/agonistas , Proteínas ras/metabolismo , Animais , Northern Blotting , Western Blotting , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Transformada , Núcleo Celular/metabolismo , Cromanos/farmacologia , Ciclina D1/antagonistas & inibidores , Ciclina D1/metabolismo , DNA Complementar/metabolismo , Relação Dose-Resposta a Droga , Fator de Crescimento Epidérmico/antagonistas & inibidores , Células Epiteliais/metabolismo , Citometria de Fluxo , Humanos , Hipoglicemiantes/farmacologia , Intestinos/citologia , Ligantes , Luciferases/metabolismo , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Ratos , Rosiglitazona , Tiazóis/farmacologia , Fatores de Tempo , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica , Ativação Transcricional , Transfecção , TroglitazonaRESUMO
To assess the developmental potential of nuclear transfer embryos in cattle using mammary gland epithelial (MGE) cells derived from the colostrum, we compared the effectiveness of cloning using those cells and fibroblast cells derived from the ear. The fusion rate of the enucleated oocytes with fibroblast cells (75 +/- 4%) was significantly higher than that with MGE cells (56 +/- 7%, P<0.05). There were no significant differences in the cleavage rate (85 +/- 3% vs. 91+/- 2%) or in the developmental rate to the blastocyst stage (35 +/- 6% vs. 35 +/- 5%) using MGE cells vs. fibroblast cells as donor nuclei (P>0.05). After transfer of blastocysts derived from nuclear transfer embryos produced using MGE cells and fibroblast cells, 13% (4/31) and 16% (6/37) of recipient heifers were pregnant on Day 42 as assessed by ultrasonography, respectively. Two of the 4 and 4 of the 6 recipients of embryos with MGE cell- and fibroblast cell-derived nuclei, respectively, aborted within 150 days of pregnancy. Four live female calves were obtained from MGE cells or fibroblast cells. However, one died from internal hemorrhage of the arteria umbilicalis. The other three calves were normal and healthy. There were no differences in the pregnancy rate or calving rate when using MGE cells vs. fibroblast cells. Microsatellite DNA analyses confirmed that the cloned calves were genetically identical to the donor cows and different from the recipient heifers. We conclude that colostrum-derived MGE cells have the developmental potential to term by nuclear transfer, and the efficiency of development of those cloned embryos was the same as that of embryos obtained using fibroblast cells as donor nuclei, although there was a significant difference in the fusion rate. This method using MGE cells derived from colostrum, which is obtained easily and safely from live adult cows, is more advantageous for cloning with somatic cells.
Assuntos
Bovinos/fisiologia , Clonagem de Organismos/veterinária , Colostro/fisiologia , Glândulas Mamárias Animais/fisiologia , Oócitos/fisiologia , Animais , Benzimidazóis/química , Bovinos/genética , Técnicas de Cultura de Células , Clonagem de Organismos/métodos , Corantes/química , Colostro/citologia , DNA/química , DNA/isolamento & purificação , Orelha Externa/citologia , Orelha Externa/fisiologia , Transferência Embrionária/veterinária , Células Epiteliais/fisiologia , Feminino , Fibroblastos/fisiologia , Imuno-Histoquímica , Queratinas/análise , Glândulas Mamárias Animais/citologia , Repetições de Microssatélites/genética , Microscopia de Fluorescência/veterinária , GravidezRESUMO
The effects of carbohydrates on meiotic maturation and ATP content of bovine oocytes under low oxygen tension (5%) were investigated. Furthermore, the developmental competence or intracellular H(2)O(2) contents of the oocytes matured under 5% or 20% O(2) was assessed. In vitro maturation of bovine cumulus-oocyte complexes was performed in synthetic oviduct fluid (SOF) containing 20 amino acids and hormones (SOFaa). The proportion of the oocytes that matured to the metaphase II stage in SOFaa containing 1.5 mM glucose, 0.33 mM pyruvate, and 3.3 mM lactate under 5% O(2) was dramatically lower than that of oocytes matured under 20% O(2) (P < 0.01). Similarly, the ATP content of the oocytes that matured under 5% O(2) was much lower than that of oocytes matured under 20% O(2) (P < 0.05). Under 5% O(2) the proportion of metaphase II oocytes increased with increasing glucose concentration (0-20 mM) in SOFaa without pyruvate or lactate. In addition, the ATP content of oocytes cultured in 20 mM glucose was higher (P < 0.05) than that of oocytes cultured in 1. 5 mM glucose. Two glucose metabolites (pyruvate and lactate) and a nonmetabolizable glucose analog (2-deoxy-glucose), however, had no noticeable effects on meiotic maturation under 5% O(2). These results suggest that ATP production under 5% O(2) is not dependent on the TCA cycle. Addition of iodoacetate, a glycolytic inhibitor, to SOFaa containing 20 mM glucose significantly reduced (P < 0.01) the proportion of metaphase II and ATP content. Moreover, the proportion of the development to the blastocyst stage of oocytes matured under 5% O(2) was higher (P < 0.05) than that of oocytes matured under 20% O(2). H(2)O(2) contents of oocytes matured under 5% O(2) was lower (P < 0.05) than that of oocytes matured under 20% O(2). The results of the present study demonstrate that glucose plays important roles in supporting the completion of meiotic maturation in bovine cumulus-oocyte complexes under low oxygen tension and that low oxygen tension during in vitro maturation is beneficial for supporting the subsequent development of bovine oocytes.
Assuntos
Meiose/fisiologia , Oócitos/fisiologia , Folículo Ovariano/fisiologia , Oxigênio/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Blastocisto/metabolismo , Dióxido de Carbono/metabolismo , Bovinos , Feminino , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Nitrogênio/metabolismoRESUMO
Intermittent intestinal bleeding persisted in a 77-year-old male, who had undergone grafting for abdominal aortic aneurysm. Each attack lasted for a few weeks and spontaneously resolved. Only a minute abnormality was found in the third portion of the duodenum; barium studies showed a segmental narrowing, but endoscopy disclosed only a small erosion in that portion. Massive and fatal gastrointestinal hemorrhage broke out 6 months after the onset of bleeding. Autopsy revealed an adhesion area with a small fistula formation between the duodenum and aorta. Even slight endoscopic findings should be considered suggestive of aortoenteric fistula in patients after aortic surgery.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Doenças da Aorta/etiologia , Duodenopatias/etiologia , Hemorragia Gastrointestinal/etiologia , Fístula Intestinal/etiologia , Complicações Pós-Operatórias/etiologia , Fístula Vascular/etiologia , Idoso , Doenças da Aorta/diagnóstico , Implante de Prótese Vascular/efeitos adversos , Duodenopatias/diagnóstico , Duodenoscopia , Evolução Fatal , Humanos , Fístula Intestinal/diagnóstico , Masculino , Complicações Pós-Operatórias/diagnóstico , Fístula Vascular/diagnósticoRESUMO
If leukocyte- and platelet-poor red cells have been processed and stored in closed bags, their delivery, especially on holidays, will be easy. The modified warm-centrifuge method was applied to a quadruple bag prepared for such purpose. Red cells were processed in the first bag by the centrifugation of whole blood. The supernatant plasma was transferred to the second bag. A phosphate buffer in the third bag was introduced into red cells and diluted red cells were then incubated at 37 degrees C for 1 h in an inverted position. After centrifugation, the red cell phase below the buffy coat layer was isolated using a Biotest separation apparatus and stored in the fourth bag (containing a preservative with adenine, phosphate, glucose and 0.9% NaCl solution) for 28 days at 4 degrees C. Ninety-eight percent of the leukocyte and 97% of platelets in whole blood unit were removed with a red cell recovery of 86%. Biochemical changes in stored red cells were similar to those of conventional buffy coat-removed red cells suspended in the same preservative, except for rapid decreases in 2,3-diphosphoglycerate levels. Since processing buffy coat-removed red cells containing few leukocytes and platelets with the present method was simple and these units might be stored for over 14 days with minimum cell damage, we suggest that the present method is useful way of processing leukocyte- and platelet-poor red cells in blood centers.