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Cladosporium cladosporioides is one of the most ubiquitous dematiaceous fungi that seldomly occur human infection. Here, we demonstrate a rare case of pulmonary phaeohyphomycosis with a distinctive pulmonary lesion during the nadir period of outpatient chemotherapy against endometrial cancer. In addition to severe neutropenia, excessive exposure to C. cladosporioides at patient's residence was considered as dominant causative factor. More caution is considered necessary for pulmonary phaeohyphomycosis in patients who receive outpatient chemotherapy and are homebound during neutropenic status.
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Absceso Pulmonar , Feohifomicosis , Humanos , Feohifomicosis/tratamiento farmacológico , Pacientes Ambulatorios , CladosporiumRESUMEN
BACKGROUND: Robot-assisted laparoscopic surgery has several advantages over conventional laparoscopy. However, population-based comparative studies for low anterior resection are limited. This article aimed to compare peri-operative results of robot-assisted low anterior resection (RALAR) and laparoscopy. METHODS: This retrospective cohort study used data from patients treated with RALAR or conventional laparoscopic low anterior resection (CLLAR) between October 2018 and December 2019, as recorded in the Japanese National Clinical Database, a data set registering clinical information, perioperative outcomes, and mortality. Of note, the registry does not include information on the tumour location (centimetres from the anal verge) and diverting stoma creation. Perioperative outcomes, including rate of conversion to open surgery, were compared between RALAR and CLLAR groups. Confounding factors were adjusted for using propensity score matching. RESULTS: Of 21 415 patients treated during the study interval, 20 220 were reviewed. Two homogeneous groups of 2843 patients were created by propensity score matching. The conversion rate to open surgery was significantly lower in the RALAR group than in the CLLAR group (0.7 versus 2.0 per cent; P < 0.001). The RALAR group had a longer operating time (median: 352 versus 283 min; P < 0.001), less intraoperative blood loss (15 versus 20 ml; P < 0.001), a lower in-hospital mortality rate (0.1 versus 0.5 per cent; P = 0.007), and a shorter postoperative hospital stay (median: 13 versus 14 days; P < 0.001) compared with the CLLAR group. The CLLAR group had a lower rate of readmission within 30 days (2.4 versus 3.3 per cent; P = 0.045). CONCLUSION: These data highlight the reduced conversion rate, in-hospital mortality rate, intraoperative blood loss, and length of postoperative hospital stay for rectal cancer surgery in patients treated using robot-assisted laparoscopic surgery compared with laparoscopic low anterior resection.
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Laparoscopía , Neoplasias del Recto , Robótica , Humanos , Japón/epidemiología , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: This study aimed to analyse the perioperative results from a national dataset of rectal cancer resections in elderly patients. METHODS: The clinical records of patients undergoing rectal cancer surgery between 2012 and 2014 were retrieved from the Japanese National Clinical Database and analysed retrospectively. Patients were categorized according to age and those 80 years or older were defined as elderly. Subgroups were also defined according to the surgical approach (laparoscopy versus open surgery). The short-term outcomes, including mortality, anastomotic leak, surgical site infections and medical complications were compared between subgroups. RESULTS: Of 56 175 patients undergoing rectal cancer surgery, some 6717 patients were elderly and laparoscopy was performed in 46.8 per cent of the sample. When comparing laparoscopy and open surgery in elderly patients, the operative mortality rate (1.5 versus 2.8 per cent; P < 0.001), the incidence of anastomotic leakage (5.2 versus 6.5 per cent; P = 0.026), surgical site infections (6.0 versus 8.0 per cent; P = 0.001), pneumonia (1.4 versus 2.5 per cent; P = 0.001), renal failure (0.7 versus 1.3 per cent; P = 0.016) and cardiac events (0.3 versus 0.8 per cent; P = 0.008) were lower for laparoscopy than for open surgery. The overall complication rate in elderly patients (19.5 per cent) was comparable to that in the younger group (P = 0.07). However, incidence of systemic complications was significantly higher in elderly than in younger patients (all P < 0.001). CONCLUSION: Laparoscopy was safe and feasible in elderly patients compared with open surgery. However, the rates of systemic complications were significantly higher than in younger patients.
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Laparoscopía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Neoplasias del Recto/cirugía , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/epidemiología , Bases de Datos Factuales , Estudios de Factibilidad , Femenino , Humanos , Japón/epidemiología , Laparoscopía/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neumonía/epidemiología , Neoplasias del Recto/mortalidad , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Resultado del TratamientoRESUMEN
AIM: To assess the pancreatic groove fat plane in the normal population and compare this with the fat plane in patients with groove pancreatitis or carcinoma using multidetector computed tomography (CT). MATERIAL AND METHODS: The pancreatic groove fat plane was evaluated retrospectively in 460 normal subjects (normal group), and in 25 patients with groove pancreatitis or carcinoma (pathology group) using 5 mm- and 1 mm-thick slices of unenhanced axial multidetector CT images. Two investigators independently assessed the degree of pancreatic groove fat plane visualisation using a four-point scale (grade 1: visualisation of 0-25%, grade 2: 26-50%, grade 3: 51-75%, grade 4: 76-100%). Pancreatic parenchymal condition, age, sex, body mass index, diabetes mellitus, and dyslipidaemia were also evaluated. RESULTS: The interobserver agreement for the visualisation grades was almost perfect (k-value = 0.95). In the normal group, grade 4 visualisation of the pancreatic groove fat plane was more common in those aged >80 years (78.6%) compared with younger age groups. Pancreatic atrophy and fatty infiltration significantly improved fat plane visualisation. In the pathology group, grade 4 visualisation of the pancreatic groove fat plane was not seen in either groove carcinoma or pancreatitis. A cut-off point of ≤50% visualisation of the pancreatic groove fat plane showed 95% sensitivity and 82% specificity for detecting possible abnormalities in older patients (>60 years). The clinical factors investigated were not significantly related to pancreatic groove fat plane visualisation. CONCLUSION: Pancreatic groove fat plane visualisation could be a good predictor for detecting groove abnormalities.
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Neoplasias Pancreáticas/diagnóstico por imagen , Pancreatitis Crónica/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Variaciones Dependientes del Observador , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Total extraperitoneal preperitoneal (TEP) repair is widely used for inguinal, femoral, or obturator hernia treatment. However, mesh repair is not often used for strangulated hernia treatment if intestinal resection is required because of the risk of postoperative mesh infection. Complete mesh repair is required for hernia treatment to prevent postoperative recurrence, particularly in patients with femoral or obturator hernia. CASES: We treated four patients with inguinocrural and obturator hernias (a 72-year-old male with a right indirect inguinal hernia; an 83-year-old female with a right obturator hernia; and 86- and 82-year-old females with femoral hernias) via a two-stage laparoscopic surgery. All patients were diagnosed with intestinal obstruction due to strangulated hernia. First, the incarcerated small intestine was released and then laparoscopically resected. Further, 8-24 days after the first surgery, bilateral TEP repairs were performed in all patients; the postoperative course was uneventful in all patients, and they were discharged 5-10 days after TEP repair. At present, no hernia recurrence has been reported in any patient. CONCLUSION: The two-stage laparoscopic treatment is safe for treatment of strangulated inguinal, femoral, and obturator hernias, and complete mesh repair via the TEP method can be performed in elderly patients to minimize the occurrence of mesh infection.
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Hernia Femoral/cirugía , Hernia Inguinal/cirugía , Hernia Obturadora/cirugía , Herniorrafia/métodos , Obstrucción Intestinal/cirugía , Laparoscopía/métodos , Anciano , Anciano de 80 o más Años , Femenino , Hernia Femoral/diagnóstico por imagen , Hernia Inguinal/diagnóstico por imagen , Hernia Obturadora/diagnóstico por imagen , Humanos , Obstrucción Intestinal/diagnóstico por imagen , Intestinos/irrigación sanguínea , Intestinos/diagnóstico por imagen , Intestinos/cirugía , Masculino , Mallas Quirúrgicas , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Apheresis platelets (APs) have gained favour over whole blood-derived platelets on the presumption that they are less likely to provoke alloimmunization to red-blood-cell antigens. CASE REPORTS: Non-D Rh antibodies appeared in three patients after apheresis platelet transfusion. Anti-C and anti-E arose in two female patients with previous antigen exposure. Both anti-c and anti-E arose in a male recipient with no prior transfusion history. MATERIALS AND METHODS: Fifty APs were analysed for residual RBCs and RBC-derived microparticles, using samples obtained from a local blood centre. Cells and microparticles were quantified with a flow cytometry gating scheme, using PE-labelled anti-CD235a (glycophorin A) and FITC-labelled anti-CD41a (platelet gp IIb/IIIa) to distinguish lineage. RESULTS: Apheresis platelets were found to contain a mean of 7·5×10(6) (95% C.I. [6·3-8·5×10(6) ]) RBCs on one manufacturer's device and 5·2×10(6) (95% C.I. [4·0-6·3×10(6) ]) RBCs on another's. RBC-derived microparticles averaged 210·7×10(6) (95% C.I. [166·2-254·2×10(6) ]) on one manufacturer's device and 232·3×10(6) (95% C.I. [194·3-272·9×10(6) ]) on another's. These counts all correspond to volumes of <1 µl. CONCLUSION: Despite RBC contamination of APs below commonly accepted thresholds for Rh immunogenicity, AP transfusion can provoke non-D Rh antibody formation. RBC-derived microparticles, smaller but more numerous than RBCs, are volumetrically comparable and may be a hitherto underappreciated antibody stimulus. Further microparticle research will guide considerations of extended phenotypic matching of platelet components.
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Incompatibilidad de Grupos Sanguíneos/sangre , Incompatibilidad de Grupos Sanguíneos/inmunología , Micropartículas Derivadas de Células/inmunología , Membrana Eritrocítica/inmunología , Isoanticuerpos , Transfusión de Plaquetas , Sistema del Grupo Sanguíneo Rh-Hr , Anciano , Eliminación de Componentes Sanguíneos , Incompatibilidad de Grupos Sanguíneos/etiología , Femenino , Humanos , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Safe peritoneal access and gastric closure are the most important concerns in clinical applications of NOTES. Our past study demonstrated usefulness of the submucosal tunnel technique for safe peritoneal access and closure with endoclips. However, such closure is sometimes difficult and time-consuming. This study investigated the feasibility of fibrin glue for submucosal tunnel closure in a NOTES porcine model. METHODS: In 10 female pigs each weighing 40 kg, transgastric peritoneoscopy was performed through a 60 mm-long submucosal tunnel created using the endoscopic submucosal dissection technique. After transgastric peritoneoscopy for 30 min, the submucosal tunnel was closed with endoclips in five pigs and fibrin glue in five pigs. After a 7 d follow-up period, the pigs were euthanized for post-mortem examination. Outcome measures included (a) technical feasibility of closure with endoclips versus fibrin glue, (b) clinical monitoring for 7 d, (c) follow-up necropsy at 7 d, and (d) histopathologic examination of the peritoneal access site. RESULTS: Transgastric peritoneoscopy with submucosal tunnel technique was successful in all pigs. Mean time required to close the mucosal incision site with fibrin glue was 1.6 ± 0.5 versus 19 ± 18.7 min with endoclips. All pigs survived well without complications. Necropsy revealed no peritonitis. There were no differences in transgastric peritoneal access sites between endoclips and fibrin glue. Histopathologic examination of the submucosal tunnel demonstrated wound healing with transmural fibrosis. No adverse effects from fibrin glue were noted. CONCLUSION: Compared with endoclips, the application of fibrin glue is easy and simple in the closure of transgastric peritoneal access in NOTES.
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Técnicas de Cierre de Herida Abdominal/instrumentación , Adhesivo de Tejido de Fibrina , Cirugía Endoscópica por Orificios Naturales/instrumentación , Peritoneo/cirugía , Estómago/cirugía , Adhesivos Tisulares , Técnicas de Cierre de Herida Abdominal/mortalidad , Animales , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Cirugía Endoscópica por Orificios Naturales/métodos , Cirugía Endoscópica por Orificios Naturales/mortalidad , Tasa de Supervivencia , Sus scrofaRESUMEN
The antimicrobial peptide LL-37 is known to have a potent LPS-neutralizing activity in monocytes and macrophages. Recently, LL-37 in gingival crevicular fluids is suggested to be the major protective factor preventing infection of periodontogenic pathogens. In this study, we tried to address the effect of LL-37 on proinflammatory responses of human gingival fibroblasts (HGFs) stimulated with Toll-like receptor (TLR)-stimulant microbial compounds. LL-37 potently suppressed LPS-induced gene expression of IL6, IL8 and CXCL10 and intracellular signaling events, degradation of IRAK-1 and IkappaBalpha and phosphorylation of p38 MAPK and IRF3, indicating that the LPS-neutralizing activity is also exerted in HGFs. LL-37 also suppressed the expression of IL6, IL8 and CXCL10 induced by the TLR3 ligand poly(I:C). LL-37 modestly attenuated the expression of IL6 and IL8 induced by the TLR2/TLR1 ligand Pam(3)CSK(4), but did not affect the expression induced by the TLR2/TLR6 ligand MALP-2. Interestingly, LL-37 rather upregulated the expression of IL6, IL8 and CXCL10 induced by another TLR2/TLR6 ligand FSL-1. Thus, the regulatory effect of LL-37 is differently exerted towards proinflammatory responses of HGFs induced by different microbial stimuli, which may lead to unbalanced proinflammatory responses of the gingival tissue to infection of oral microbes.
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Péptidos Catiónicos Antimicrobianos/farmacología , Quimiocina CXCL10/biosíntesis , Fibroblastos/efectos de los fármacos , Interleucina-6/biosíntesis , Interleucina-8/biosíntesis , Infecciones Bacterianas/inmunología , Células Cultivadas , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Fibroblastos/inmunología , Fibroblastos/metabolismo , Fibroblastos/patología , Regulación de la Expresión Génica , Encía/patología , Humanos , Inmunidad Innata , Quinasas Asociadas a Receptores de Interleucina-1/antagonistas & inhibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Ligandos , Enfermedades Periodontales/inmunología , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 2/inmunología , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 3/inmunología , Receptor Toll-Like 3/metabolismo , Receptor Toll-Like 4/inmunología , Receptor Toll-Like 4/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , CatelicidinasRESUMEN
We report the observation of extremely efficient energy transfer (greater than 99%) in an organic-inorganic hybrid quantum-well structure consisting of perovskite-type lead bromide well layers and naphthalene-linked ammonium barrier layers. Time-resolved photoluminescence measurements confirm that the transfer is triplet-triplet Dexter-type energy transfer from Wannier excitons in the inorganic well to the triplet state of naphthalene molecules in the organic barrier. Using measurements in the 10-300 K temperature range, we also investigated the temperature dependence of the energy transfer.
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BACKGROUND: Laparoscopy-assisted distal gastrectomy (LAG) is gaining acceptance for treating early gastric cancer. However, the long-term quality of life after LAG for gastric cancer is unknown. This study compared the long-term quality of life after LAG versus open distal gastrectomy (ODG) for early gastric cancer. METHOD: This study included 53 patients who underwent LAG and 37 patients who underwent ODG for treatment of early gastric cancer. Quality of life was evaluated on the basis of a 22-item questionnaire that addressed food tolerance and mental and physical conditions, scored on a scale of 1-3. RESULTS: The mean follow-up periods after LAG and ODG were 99.3 and 97.0 months, respectively. Although the majority of patients who had undergone LAG were consuming a normal diet and had weight loss of less than 5 kg, all 22 items and the total score of the LAG group were comparable to those of the ODG group. However, the incidence of postoperative intestinal obstruction was significantly lower in the LAG group than in the ODG group (1% vs. 13%, p < 0.05). CONCLUSIONS: LAG is equivalent to ODG with respect to long-term quality of life and is associated with a reduced incidence of postoperative intestinal obstruction.
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Gastrectomía/métodos , Laparoscopía , Calidad de Vida , Neoplasias Gástricas/cirugía , Anciano , Dieta , Femenino , Estudios de Seguimiento , Gastrectomía/efectos adversos , Humanos , Incidencia , Obstrucción Intestinal/epidemiología , Obstrucción Intestinal/etiología , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Pérdida de PesoRESUMEN
Chronic periodontitis is correlated with Porphyromonas gingivalis infection. In this study, we found that the expression of secretory leucocyte protease inhibitor (SLPI), an endogenous inhibitor for neutrophil-derived proteases, was reduced in gingival tissues with chronic periodontitis associated with P. gingivalis infection. The addition of vesicles of P. gingivalis decreased the amount of SLPI in the media of primary human gingival keratinocytes compared to untreated cultures. We therefore investigated how arginine-specific gingipains (Rgps) affect the functions of SLPI, because Rgps are the major virulence factors in the vesicles and cleave a wide range of in-host proteins. We found that Rgps digest SLPI in vitro, suppressing the release of SLPI. Rgps proteolysis of SLPI disrupted SLPI functions, which normally suppresses neutrophil elastase and neutralizes pro-inflammatory effects of bacterial cell wall compounds in cultured human gingival fibroblasts. The protease inhibitory action of SLPI was not exerted towards Rgps. These results suggest that Rgps reduce the protective effects of SLPI on neutrophil proteases and bacterial proinflammatory compounds, by which disease in gingival tissue may be accelerated at the sites with P. gingivalis infection.
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Adhesinas Bacterianas/farmacología , Cisteína Endopeptidasas/farmacología , Encía/metabolismo , Líquido del Surco Gingival/metabolismo , Periodontitis/metabolismo , Porphyromonas gingivalis/fisiología , Proteínas/metabolismo , Adhesinas Bacterianas/análisis , Células Cultivadas , Enfermedad Crónica , Cisteína Endopeptidasas/análisis , Progresión de la Enfermedad , Electroforesis en Gel de Poliacrilamida , Cisteína-Endopeptidasas Gingipaínas , Encía/inmunología , Encía/microbiología , Líquido del Surco Gingival/microbiología , Humanos , Immunoblotting , Interleucina-8/análisis , Persona de Mediana Edad , Periodontitis/inmunología , Periodontitis/microbiología , Proteínas Inhibidoras de Proteinasas Secretoras , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Inhibidor Secretorio de Peptidasas Leucocitarias , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Conventional open gastrectomy has been reported to result in increased morbidity in obese patients. To date, there has been no study evaluating laparoscopic gastrectomy in such patients; therefore, we assessed the short-term results of this procedure in a group of obese patients. METHODS: The study included 99 consecutive patients who underwent laparoscopy-assisted distal gastrectomy (LDG) for the cure of early gastric cancer. The patients were divided into two groups: obese (body mass index [BMI] > or =25.0, n = 16) and nonobese (BMI <25.0, n = 83). Patient characteristics, operative details, and postoperative outcomes were compared and analyzed. RESULTS: Patient characteristics, including age, sex, American Society of Anesthesiologists (ASA) status, and disease stage, were not different between obese and nonobese patients. Operating time was significantly longer in obese patients than in nonobese patients (271 vs 239 min, p < 0.05). However, there was no significant difference between obese and nonobese patients in time to first flatus (3.7 vs 3.3 days), time to solid diet (6.3 vs 5.2 days), length of postoperative hospital stay (18.7 vs 17.9 days), or frequency of major (25% vs 16%) and minor (19% vs 12%) postoperative complications. There were no conversions to conventional open surgery and no perioperative deaths. CONCLUSION: The only difference between our two study groups was that LDG required a longer operating time in obese patients; morbidity and length of hospital stay were not increased. Thus, we believe that LDG is likely to become the treatment of choice for obese patients with early gastric cancer.
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Gastrectomía/métodos , Laparoscopía/métodos , Obesidad/complicaciones , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Open gastrectomy is associated with increased morbidity and a longer hospital stay than laparoscopically assisted gastrectomy. The aim of this study was to clarify the value of laparoscopically assisted distal gastrectomy (LDG) in the elderly, in whom co-morbid disease is generally more common. METHODS: Forty-five elderly patients (aged 70 years or more) and 57 younger patients who underwent LDG, and 28 elderly patients who underwent open distal gastrectomy (ODG) for early gastric cancer between January 1994 and April 2003 were studied. Demographics and postoperative outcomes were compared. RESULTS: : Co-morbidity was more common in elderly patients than in younger patients who underwent LDG (25 of 45 versus 16 of 57; P = 0.004). The postoperative complication rate, time to solid diet and postoperative hospital stay were similar in these two groups. Elderly patients who underwent LDG had a significantly reduced medical complication rate (two of 45 versus six of 28; P = 0.023), time to first flatus (3.7 versus 4.2 days; P = 0.042), time to solid diet (4.6 versus 5.5 days; P = 0.011) and postoperative hospital stay (16.3 versus 23.9 days; P = 0.011) than elderly patients who had ODG. CONCLUSION: LDG offers particular advantages to elderly patients with early gastric cancer, including rapid return of gastrointestinal function, fewer complications and a shorter hospital stay.
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Gastrectomía/métodos , Laparoscopía/métodos , Neoplasias Gástricas/cirugía , Anciano , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Complicaciones Intraoperatorias/etiología , Masculino , Metástasis de la Neoplasia , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: The effect of carbon dioxide (CO(2)) pneumoperitoneum on the liberation of cancer cells from the primary tumor is not clear. This study investigated the influence of laparotomy versus CO(2) pneumoperitoneum on the progression of colon cancer with serosal invasion in a mouse model. METHODS: Pieces of human colon adenocarcinoma (HT29) tumor were implanted in the cecal wall of 45 BALB/c nude mice. Each mouse underwent one of three procedures: laparotomy, CO(2) pneumoperitoneum, or anesthesia (control). Three weeks later, the size and weight of cecal tumors, the number of nodules, and the tumor volume score of peritoneal dissemination were examined. Another 45 mice were treated in the same way. The cecal tumor was resected on days 1, 3, or 5 after treatment. Total RNA was isolated from the resected tumors. The expression of E-cadherin and beta-1 integrin messenger RNA (mRNA) was examined by semiquantitative real-time reverse transcriptase-polymerase chain reaction assay. RESULTS: Significantly more nodules of peritoneal dissemination were found in the laparotomy group than in the control group (p < 0.05). The tumor volume score of peritoneal dissemination in the laparotomy group was significantly higher than in the other two groups (p < 0.05). The expression of E-cadherin mRNA at day 5 in the laparotomy group was significantly less than in the other two groups (p < 0.05). There were no differences in beta-1 integrin among three groups. CONCLUSIONS: Peritoneal dissemination was more extensive after laparotomy than after CO(2) pneumoperitoneum in a mouse model of cecal cancer with serosal invasion. Decreased expression of E-cadherin mRNA in tumors after laparotomy, but not after CO(2) pneumoperitoneum, may be associated with the increase in peritoneal dissemination.
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Adenocarcinoma/secundario , Dióxido de Carbono/efectos adversos , Neoplasias del Ciego/patología , Modelos Animales de Enfermedad , Laparotomía/efectos adversos , Siembra Neoplásica , Neoplasias Peritoneales/secundario , Neumoperitoneo Artificial/efectos adversos , Animales , Masculino , Ratones , Ratones Endogámicos BALB C , Invasividad NeoplásicaRESUMEN
The molecular mechanism that causes non-adhesive, discoid platelets to transform into sticky dendritic bodies that form blood clumps is a complex series of events. Recently it has become clear that lipid microdomains--also known as rafts--play a crucial role in this process. We have used a non-cytolytic derivative of perfringolysin-O, a cholesterol binding cytolysin, that binds selectively to cholesterol-rich membrane domains, combined with confocal- and immunoelectron microscopy to visualize cholesterol-raft dynamics during platelet adhesion. In resting platelets cholesterol was uniformly distributed on the cell surface and confined to distinct intracellular compartments (i.e. multivesicular bodies, dense granules, and the internal membranes of alpha-granules). Upon interaction with fibrinogen, cholesterol accumulated at the tips of filopodia and at the leading edge of spreading cells. Stimulation with thrombin receptor activating peptide (TRAP) resulted in a similar redistribution of cholesterol towards filopodia. The adhesion-dependent raft aggregation was accompanied by concentration of the tyrosine kinase c-Src and the tetraspanin CD63 in these domains, whereas glycoprotein Ib (GPIb) was not selectively targeted to the raft clusters. c-Src, the tetraspanin CD63, and GPIb were recovered in biochemically isolated low-density membrane fractions. Disruption of rafts by depleting membrane cholesterol had no effect on platelet shape change but inhibited platelet spreading on fibrinogen and TRAP-induced aggregation. Our results demonstrate that cholesterol rafts in platelets are dynamic entities in the membrane that co-cluster with the tyrosine kinase c-Src and the costimulatory molecule CD63 in specialized domains at the cell surface, thereby providing a possible mechanism in functioning as signaling centres.
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Antígenos CD/metabolismo , Plaquetas/ultraestructura , Microdominios de Membrana/fisiología , Fosfotransferasas/metabolismo , Glicoproteínas de Membrana Plaquetaria/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Seudópodos/química , beta-Ciclodextrinas , Plaquetas/química , Plaquetas/fisiología , Proteína Tirosina Quinasa CSK , Tamaño de la Célula , Colesterol/metabolismo , Colesterol/fisiología , Ciclodextrinas/farmacología , Fibrinógeno , Humanos , Inmunohistoquímica , Microdominios de Membrana/química , Fosforilación , Activación Plaquetaria , Transporte de Proteínas , Proteínas Tirosina Quinasas , Receptores de Trombina , Tetraspanina 30 , Familia-src QuinasasRESUMEN
The sensitivity to heat and chemical modification of human retinoblastoma cells obtained from patients with primary retinoblastoma was studied in vitro by the human tumour colony assay established by Hamburger and Salmon in 1977. Retinoblastoma cells showed moderate sensitivity to 1 h of hyperthermia at 42 degrees C; the median T/C% (ratio of the colony number in treated vs. control dishes, x 100) under hyperthermia was 47.0% for 46 tumours studied. When tumours were treated with melphalan, cis-diamminedichloroplatinum (II), adriamycin, etoposide and teniposide at 37 degrees C and 42 degrees C, the median T/C% for each chemical agent was decreased significantly by concomitant hyperthermia. One-hour exposure of 38 tumours to melphalan, cis-diamminedichloroplatinum (II) (30 tumours), adriamycin (27 tumours), teniposide (22 tumours) and etoposide (20 tumours) at 37 degrees C gave median T/C%s of 9.5, 33.5, 16.0, 3.8 and 38.0%, respectively, while exposure at 42 degrees C gave values of 2.4, 8.2, 5.6, 1.0 and 6.6%, respectively. Combination of heat and chemical treatment with melphalan, cis-diamminedichloroplatinum (II) and etoposide appeared to be synergistic with median T/C%s that were significantly lower than the median T/C%s expected from a simple sum of their individual effects. These in vitro results suggest that combining the treatment modalities of hyperthermia and chemotherapy for primary retinoblastoma would be advantageous.
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Hipertermia Inducida , Neoplasias de la Retina , Retinoblastoma , Antineoplásicos/farmacología , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Fitogénicos/farmacología , Supervivencia Celular/efectos de los fármacos , Preescolar , Cisplatino/farmacología , Doxorrubicina/farmacología , Etopósido/farmacología , Enucleación del Ojo , Femenino , Calor , Humanos , Técnicas In Vitro , Lactante , Masculino , Melfalán/farmacología , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
BACKGROUND AND AIM: Current evidence suggests a possible relationship between DNA ploidy status and Ki-ras gene mutations in human cancers. However, the conventional method does not enable accurate determination of DNA ploidy status of a tumor cell. The present study attempts to clarify whether Ki-ras gene mutations are associated with DNA ploidy status in sporadic colorectal carcinomas using a crypt isolation technique coupled with DNA cytometric sorting. METHODS: Polymerase chain reaction and single-strand conformation polymorphism and direct sequencing were used to analyze Ki-ras gene mutations in 82 sporadic colorectal carcinomas: 21 diploid, 12 aneuploid, and 49 multiploid. In addition, microsatellite instability (MSI) was assessed using seven microsatellite markers to study the relationship to Ki-ras mutations. RESULTS: Ki-ras mutations were found in 12 of 21 diploid carcinomas and in 8 of 12 aneuploid carcinomas. In contrast, Ki-ras gene mutations were detected infrequently in the 34 multiploid carcinomas examined, 8 of which were seen in diploid populations and 10 in aneuploid populations. On the other hand, Ki-ras gene mutations were inversely correlated with MSI, which was found in diploid carcinomas only. CONCLUSIONS: The low frequency of Ki-ras gene mutations that we observed in multiclonal colorectal carcinomas suggests that development of multiclonal colorectal carcinoma may involve a mechanism different from that involved in the development of diploid or aneuploid colorectal carcinomas.
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Neoplasias Colorrectales/genética , ADN de Neoplasias/análisis , Genes ras , Adulto , Anciano , Anciano de 80 o más Años , Aneuploidia , Neoplasias Colorrectales/ultraestructura , ADN de Neoplasias/clasificación , Diploidia , Femenino , Citometría de Flujo , Humanos , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Mutación , PoliploidíaRESUMEN
Pre-operative evaluation of esophageal infiltration is sometimes difficult in patients with advanced thyroid cancer even with recent imaging modalities. We evaluated the accuracy of endoscopic ultrasonography (EUS) in diagnosing esophageal infiltration of thyroid cancer. Twenty-nine patients with advanced thyroid cancer underwent EUS and other imaging examinations before surgery. The diagnostic accuracy of EUS was compared with that of magnetic resonance imaging (MRI) and esophagography based on pathologic findings in 27 of the 29 cases. EUS clearly demonstrated the 5-layer structure of the esophageal wall. EUS detected cancer invasion into the muscularis propria of the esophagus correctly in 8 of 10 patients diagnosed pathologically with muscular infiltration. EUS was significantly more accurate than MRI and esophagography (88.9% vs 63.0% and 66.7%, respectively). The specificity of EUS was also significantly better than the specificities of MRI or esophagography (94.1% vs 58.8% and 64.7%, respectively). The sensitivity, positive predictive value and negative predictive value of EUS tended to be better than those of MRI and esophagography. EUS is useful in evaluating the esophageal infiltration of thyroid cancer. This method has the further advantage of detecting the exact depth of cancer invasion into the esophageal wall.