RESUMEN
BACKGROUND: The extent of endoscopic sinus surgery (ESS) required for optimal outcomes in chronic rhinosinusitis (CRS) is undefined. We evaluated whether concordance between the extent of surgery and degree of radiographic disease influences postoperative outcomes. METHODS: 247 CRS patients who underwent ESS were retrospectively assigned a concordance score reflecting the similarity between the extent of surgery and degree of radiographic disease. 0 points were assigned when sinusotomy was performed on a diseased sinus, or no sinusotomy was performed on a nondiseased sinus; plus 1 for sinusotomy on a nondiseased sinus; and -1 for a diseased sinus left unopened. The total possible score ranged from minus 10 to plus 10. Patients were divided into 5 subgroups according to variance from complete concordance. SNOT-22 scores and revision rates were compared at 6 and 24 months. RESULTS: All five subgroups had similar preoperative SNOT-22 scores and improved at 6 months postoperatively. At 6 months postoperatively, the most conservatively operated and most extensively operated subgroups each achieved equivalent improvements in SNOT-22 as the completely concordant subgroup. At 24 months, the most extensively operated subgroup had a 12.5-point smaller improvement in SNOT-22 scores compared to the completely concordant subgroup. Multivariate analysis showed no association between concordance score and revision rate. CONCLUSIONS: Symptom improvement and revision rates after ESS do not appear to correlate with the degree of concordance between extent of surgery and radiographic disease. More extensive surgery than indicated by CT confers neither greater symptomatic improvement nor long-term detriment.
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Endoscopía , Procedimientos Quírurgicos Nasales , Senos Paranasales/cirugía , Rinitis/cirugía , Sinusitis/cirugía , Enfermedad Crónica , Humanos , Radiografía , Estudios Retrospectivos , Rinitis/diagnóstico por imagen , Sinusitis/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.
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Adulto , Femenino , Humanos , Masculino , Asma/inducido químicamente , Genes MHC Clase I/genética , Genes MHC Clase II/genética , Isocianatos/toxicidad , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Asma/genética , Variación Genética , Genotipo , Enfermedades Profesionales/genética , Polimorfismo de Nucleótido Simple , RiesgoRESUMEN
Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.
Asunto(s)
Apoptosis/efectos de los fármacos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , PPAR gamma/metabolismo , Neoplasias Gástricas/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , PPAR gamma/genética , Transducción de Señal , Neoplasias Gástricas/metabolismo , Activación Transcripcional , Regulación hacia ArribaRESUMEN
OBJECTIVES: The aim of this study was to elucidate the role of 6-6 bieckol (EB1) and pholorofucofuroeckol-A (EB5) from brown seaweed marine algae (Eisenia bicyclis) on lipopolysaccharide (LPS)-induced inflammation in human dental pulp cells (HDPCs). METHODS: The cytotoxicity of EB1 and EB5 was examined by MTT assay on LPS-induced human dental pulp cells. Their role on expression of inflammatory, odontogenic, and osteogenic molecules was determined by Western blot analysis. The dentin mineralization was checked by alkaline phosphatase activity. RESULTS: The five compounds from E. bicyclis have different structure with non-cytotoxic in HDPCs. EB1 and EB5 showed anti-inflammatory properties and inhibited phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) and phosphorylated-c-jun N-terminal kinases (p-JNK) without any cytotoxicity. In particular, EB1 inhibited cyclooxygenase-2 (COX-2) and p-ERK1/2 signaling, and EB5 inhibited only p-ERK1/2 signaling but not COX-2. Both compounds inhibited nuclear factor kappa-B (NF-κB) translocation. Furthermore, EB1 and EB5 increased dentinogenic and osteogenic molecules, and dentin mineralized via alkaline phosphatase activity (ALP) in LPS-induced HDPCs. CONCLUSIONS: This study elucidates that EB1 and EB5 have different types of anti-inflammatory property and help in dentin formation. Therefore, these compounds derived from marine algae of E. bicyclis may be used as selective therapeutic strategies for pulpitis and oral diseases.
Asunto(s)
Pulpa Dental/patología , Inflamación/patología , Sistema de Señalización de MAP Quinasas , Células Cultivadas , Inhibidores de la Ciclooxigenasa 2/farmacología , Pulpa Dental/enzimología , Humanos , Inflamación/enzimología , Algas MarinasRESUMEN
OBJECTIVES: Heme oxygenase-1 (HO-1) is contributed to odontoblast differentiation in human dental pulp cells (HDPCs). In this study, pachymic acid from mushroom Formitopsis niagra is examined to determine whether it affects pulpal inflammation and promotes odontogenesis via HO-1 gene expression. MATERIALS AND METHODS: The HDPCs were given H2O2 for inflammation. The anti-inflammatory character and odontoblast differentiation by pachymic acid were analyzed by Western blotting, alkaline phosphatase activity, and alizarin red S staining. To understand the mechanism of pachymic acid via HO-1 induction, the cells were treated with zinc protoporphyrin IX (ZnPP: HO-1 inhibitor). RESULTS: H2O2 induced pulp inflammation and disturbed odontoblast differentiation. However, the HDPCs treated with pachymic acid affected anti-inflammatory effect and induction of odontoblast differentiation through increasing HO-1 expression. In addition, pachymic acid has potent cytoprotection and mineralization under H2O2 treatment. Furthermore, pachymic acid significantly suppressed nuclear factor-kappa B (NF-κB) translocation into nucleus and induced NE-E2-related factor-2 (Nrf2) translocation into nucleus. Overall, NF-κB and Nrf2 translocation were regulated by the HO-1 pathway. CONCLUSIONS: The pachymic acid showed anti-inflammatory function and odontoblast differentiation via HO-1 pathway. These results suggested that pachymic acid may be applicable for prevention of oral inflammation or to improve dentin mineralization against several stresses.
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Antiinflamatorios/farmacología , Diferenciación Celular/efectos de los fármacos , Pulpa Dental/citología , Hemo-Oxigenasa 1/fisiología , Odontoblastos/citología , Triterpenos/farmacología , Células Cultivadas , HumanosRESUMEN
We describe the development of an aerosol system for topical gene delivery to the lungs of C57BL/6 mice. This system is based on the combination of the commercial cationic lipid Lipofectin with a novel amphiphilic triblock copolymer, poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol) (PPDO/PLLA-b-PEG, and abbreviated in the text as polymeric micelles). After optimizing conditions for DNA delivery to the lungs of mice using the combination of polymeric micelles with Lipofectin and LacZ DNA, we used the Lipofectin/polymeric micelle system to deliver the tumor suppressor gene PTEN to the lungs of C57BL/6 mice bearing the B16-F10 melanoma. Lipofectin/PTEN/polymeric micelles significantly improved gene expression of PTEN in the lungs of mice with no evidence of cell toxicity or acute inflammation. Importantly, lung metastasis, as measured by lung weight, was significantly reduced (P<0.001), as were total tumor foci in the lungs (P<0.001) and size of individual tumor nodules in animals treated with Lipofectin/PTEN/polymeric micelles compared with control animals. Survival time was also extended. These results suggest that the Lipofectin/polymeric micelle system is appropriate for enhancing gene delivery in vivo and that it can be applied as a non-invasive gene therapy for lung cancer.
Asunto(s)
Terapia Genética/métodos , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Melanoma Experimental/terapia , Fosfohidrolasa PTEN/genética , Poliésteres , Polietilenglicoles , Aerosoles , Animales , Femenino , Expresión Génica , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Melanoma Experimental/metabolismo , Melanoma Experimental/secundario , Ratones , Ratones Endogámicos C57BL , Micelas , Fosfohidrolasa PTEN/análisis , Fosfohidrolasa PTEN/metabolismo , Fosfatidiletanolaminas , Transfección/métodos , TransgenesRESUMEN
AIM: The effects of cold exposure on gene and protein expression of vascular endothelial growth factor (VEGF), in heart and skeletal muscles, were studied in male adult Wistar rats. METHODS: Cold immersion was accomplished by submerging the rats in shoulder-deep water maintained at approximately 18 degrees C, either acutely (1 h) or chronically (1 h day(-1), 5 days week(-1) for 20 weeks). The expressions of VEGF mRNA and protein in heart, gastrocnemius, and soleus muscles were examined by Northern and Western blotting and competitive-polymerase chain reaction techniques. RESULTS: The expressions of VEGF mRNA and protein were markedly increased in cardiac muscle of the cold-immersed group, particularly in the 1-hour exposure group, whereas VEGF mRNA and protein in gastrocnemius were decreased significantly after an acute exposure. Although the protein level in gastrocnemius remained low in the chronically exposed group, the expression of mRNA of VEGF(165) with chronic exposure in this group returned to the control level and that of VEGF(206) was 15% greater than that in controls. The expression of mRNA for VEGF(165) in soleus was also lowered by acute cold exposure, although that for VEGF(206) was stable. However, VEGF protein was increased by 50%. After 20 weeks, all of these parameters were increased over the levels found in the controls. CONCLUSION: These results suggest that the VEGF gene may be a major regulatory factor in cardiac and skeletal muscle adaptation to the cold environment stimulating angiogenesis and thermogenesis.
Asunto(s)
Frío , Corazón/fisiopatología , Inmersión/fisiopatología , Músculo Esquelético/fisiopatología , ARN Mensajero/genética , Factor A de Crecimiento Endotelial Vascular/análisis , Actinas/análisis , Animales , Regulación de la Expresión Génica/genética , Masculino , Proteínas Musculares/análisis , Proteínas Musculares/genética , Miocardio/química , Ratas , Ratas Wistar , Factor A de Crecimiento Endotelial Vascular/genética , AguaRESUMEN
To determine incidence of invasive Haemophilus influenzae type b (Hib) disease in a defined population of Jeonbuk Province, Korea, children <5 years were evaluated in prospective, population-based surveillance of invasive bacterial diseases using standardized methods for patient referral, clinical evaluation and laboratory testing (optimized culture, latex agglutination, polymerase chain reaction). Vaccine utilization was assessed with vaccination histories of patients in surveillance, monthly data on Hib vaccine distribution and a coverage survey of clinic patients in study population. From September 1999 to December 2001, 2176 children were evaluated for possible meningitis, 1541 had no cerebrospinal fluid (CSF) findings of meningitis, 605 had CSF abnormalities (suspected bacterial meningitis) but no pathogen identified; six patients had probable Hib meningitis and eight had confirmed Hib meningitis. The annual suspected bacterial meningitis incidence was 258.4/100,000 <5 years and the probable/confirmed Hib meningitis incidence was 6.0/100,000 <5 years. Pneumococcal meningitis incidence was 2.1/100,000 <5 years and Group B streptococcal meningitis incidence was 0.17/1000 live births. A total of 69,589 Hib vaccine doses were distributed during the study. Hib vaccine coverage was negligible initially but increased to 16% (complete Hib immunization) and 27% (partial immunization) in final months of study. Suspected bacterial meningitis incidence was high but proven invasive Hib meningitis incidence was low. Hib was leading cause of bacterial meningitis yet bacterial pathogens were identified in only 4% of abnormal CSF. These findings may reflect truly low incidence, presumptive antibiotic treatment, partial Hib immunization, or incomplete clinical evaluations. Given the apparent Hib meningitis burden in Jeonbuk Province, additional studies to describe other invasive Hib syndromes, Hib-associated mortality and disability, and economic impact of Hib disease will be useful to guide public health decisions regarding routine Hib vaccine introduction.
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Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/prevención & control , Haemophilus influenzae tipo b , Meningitis Bacterianas/epidemiología , Meningitis por Haemophilus/epidemiología , Adolescente , Adulto , Líquido Cefalorraquídeo/microbiología , Niño , Preescolar , Femenino , Infecciones por Haemophilus/microbiología , Vacunas contra Haemophilus , Haemophilus influenzae tipo b/aislamiento & purificación , Humanos , Incidencia , Lactante , Recién Nacido , Corea (Geográfico)/epidemiología , Masculino , Meningitis Bacterianas/microbiología , Meningitis Bacterianas/prevención & control , Meningitis por Haemophilus/microbiología , Persona de Mediana Edad , Estudios Prospectivos , Streptococcus agalactiae/aislamiento & purificación , Streptococcus pneumoniae/aislamiento & purificación , Vacunas ConjugadasRESUMEN
Insulin-like growth factor (IGF)-I and -II are potent mitogens and postulated to exert autocrine, and paracrine effects on growth regulation in human gastric cancer. Their mitogenic effects are tightly regulated by the IGF binding proteins (IGFBPs). In this study, we evaluated the mRNA expression of IGF-I, IGF-II and the IGFBPs in a panel of human gastric cancer cell lines, and normal and tumour tissue specimens from patients with gastric cancer by reverse transcriptase-polymerase chain reaction (RT-PCR) and competitive PCR. Conditioned media (CM) of the gastric cancer cell lines were studied for the secretion of the IGFBPs by western ligand blot (WLB) and western immunoblot (WIB). IGF-I and IGF-II were expressed in all of the gastric cancer cell lines, and the normal and tumour tissue specimens. Overexpression of the IGFs, in particular, IGF-II, was observed in the tumour tissues. The expression pattern of IGFBPs was heterogeneous among the gastric cancer cell lines. IGFBP-2 was expressed in all of the gastric cancer cell lines, whereas IGFBP-1 was not detected in any cell lines. IGFBP-4 was expressed in the most of cell lines. IGFBP-3, IGFBP-5 and IGFBP-6 were expressed in approximately 50% of cell lines. In addition, exogenous IGF-I and IGF-II stimulated the proliferation of gastric cancer cells, suggesting the existence of a functional IGF system in gastric cancer. Taken together, our data-suggest that the IGF-IGFBP system may play an important role in the initiation, progression and metastasis of gastric cancer. Further studies are needed to understand the exact role of IGFs and IGFBPs in gastric neoplasia.
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Adenocarcinoma/metabolismo , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Somatomedinas/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/patología , Western Blotting , División Celular/efectos de los fármacos , Expresión Génica , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/farmacología , Proteínas de Neoplasias/metabolismo , ARN Mensajero/genética , ARN Neoplásico/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/patología , Células Tumorales CultivadasRESUMEN
PTEN/MMAC1/TEP1 (PTEN) is a tumor suppressor gene that is mutated in a variety of advanced and metastatic cancers, strongly suggests that PTEN alteration is possibly involved in the tumor progression and formation of metastases. However, the roles of PTEN in tumor growth and metastasis and its functional mechanisms are not fully understood. We evaluated the tumor suppressor function of PTEN gene on tumor growth and metastasis in vitro and in vivo. Our results of in vitro soft agar assay and in vivo PTEN-expressing tumor cell growth showed that PTEN inhibited the tumorigenicity of B16F10 melanoma cells. Anti-metastatic function of PTEN was also revealed by experimental pulmonary metastatic animal model. For the further insight into the mechanisms underlying the PTEN-mediated inhibition of tumor metastasis, we have examined the role of PTEN on the secretion of matrix metalloproteinases (MMPs), insulin-like growth factors (IGFs) and the expression of secretory and cellular vascular endothelial growth factor (VEGF) proteins that have been described to contribute to the metastasis of tumor. PTEN significantly lowered MMPs and IGFs secretion and also expression of secretory and cellular VEGF proteins. These results suggest that PTEN tumor suppressor protein inhibits tumorigenicity and metastasis through regulation of MMP, IGFs, and VEGF expression.
Asunto(s)
Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/fisiología , Proteínas Supresoras de Tumor , Animales , Northern Blotting , Western Blotting , División Celular , ADN Complementario/metabolismo , Electroforesis en Gel de Poliacrilamida , Factores de Crecimiento Endotelial/biosíntesis , Femenino , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Factor II del Crecimiento Similar a la Insulina/biosíntesis , Linfocinas/biosíntesis , Metaloproteinasas de la Matriz/metabolismo , Melanoma Experimental , Ratones , Ratones Endogámicos C57BL , Mutación , Metástasis de la Neoplasia , Fosfohidrolasa PTEN , Monoéster Fosfórico Hidrolasas/biosíntesis , Radioinmunoensayo , Factores de Tiempo , Transfección , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
Despite innovations in surgical treatment of frontal sinus disease, medical therapy continues to be important. Preoperative, perioperative, and postoperative considerations are discussed. Diagnostic criteria, microbiology, and complications associated with frontal rhinosinusitis are also reviewed.
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Sinusitis Frontal/terapia , Enfermedad Aguda , Administración Intranasal , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Enfermedad Crónica , Sinusitis Frontal/diagnóstico , Sinusitis Frontal/cirugía , Humanos , Monitoreo Intraoperatorio , Postura , EsteroidesRESUMEN
Endoscopic trans-septal frontal sinusotomy (TSFS) represents a unique surgical approach to the floor of the frontal sinus. Although the final result can have similarities to the modified Lothrop procedure in that the intersinus septum may be drilled out, endoscopic TSFS represents a novel approach that can be valuable in patients with certain anatomic configurations. Endoscopic TSFS represents an alternate approach to the frontal sinus that may be used by the experienced endoscopist to augment treatment of refractory frontal sinus disease. This procedure is best considered for patients with favorable anatomy who have significant frontal sinus disease and cannot be managed adequately through an endoscopic frontal sinusotomy.
Asunto(s)
Seno Frontal/cirugía , Tabique Nasal/cirugía , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Seno Frontal/diagnóstico por imagen , Humanos , Tabique Nasal/diagnóstico por imagen , Enfermedades de los Senos Paranasales/diagnóstico , Enfermedades de los Senos Paranasales/cirugía , Cuidados Posoperatorios , Cuidados Preoperatorios , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Wegener's granulomatosis is a systemic vasculitis that can affect any organ system, but primarily involves the upper and lower respiratory tracts and the kidneys. Chronic sinusitis is a well-known clinical feature of the disease. Mucosal abnormalities of the nose and paranasal sinuses have been well-characterized and range from granulomatous lesions to diffuse mucosal thickening. In contrast, abnormalities of the underlying bone of the paranasal sinuses in this disease have not been well-described, and reports have been limited. To characterize bony abnormalities of the nose and paranasal sinuses in patients with Wegener's granulomatosis, we performed a retrospective review of all patients with Wegener's granulomatosis who underwent a sinus CT scan at our institution between 1989 and 1999. Nine patients were identified. A total of 22 distinct bony abnormalities were identified in 5 patients. Specific bony findings included bony erosion and destruction of the septum and turbinates; erosion of the ethmoid sinuses; neo-osteogenesis of the maxillary, frontal, and sphenoid sinuses; and complete bony obliteration of the maxillary, frontal, and sphenoid sinuses. Although these findings are suggestive of Wegener's granulomatosis, they are not pathognomonic. Bony changes on sinus CT scan may provide radiologic evidence of underlying Wegener's granulomatosis when clinical suspicion is high.
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Huesos Faciales/diagnóstico por imagen , Granulomatosis con Poliangitis/diagnóstico por imagen , Senos Paranasales/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Senos Etmoidales/diagnóstico por imagen , Senos Etmoidales/patología , Huesos Faciales/patología , Femenino , Humanos , Masculino , Osteogénesis , Estudios RetrospectivosRESUMEN
Receptors for the constant region of IgG, Fc gamma receptors, are expressed on the surface of hematopoietic cells, where they mediate signaling events, such as phagocytosis, essential for host defense. Fc gamma receptors also play a role in the pathophysiology of autoimmune diseases. We have demonstrated that members of each of the three classes of human Fc gamma receptors, Fc gamma RI, Fc gamma RII, and Fc gamma RIII, mediate phagocytosis, but that important differences exist in their requirements for phagocytic signaling. For example, the Fc gamma receptors Fc gamma RI and Fc gamma RIIIA induce signaling largely by association with a gamma subunit containing a conserved cytoplasmic motif (ITAM) whose tyrosines are phosphorylated following receptor stimulation. Fc gamma RIIA contains a similar motif in its own cytoplasmic domain and does not require the gamma chain for phagocytic signaling. The tyrosine kinase Syk associates with the cytoplasmic domain of both the Fc gamma receptor gamma chain and Fc gamma RIIA and is required for phagocytosis by both Fc gamma receptor systems. To elucidate the differences in phagocytic signaling by the gamma chain and Fc gamma RIIA, we investigated the requirements for Fc gamma receptor/Syk co-immunoprecipitation, tyrosine phosphorylation, and phagocytosis. Both Fc gamma RIIA and the human gamma chain contain a tyrosine seven amino acids upstream of the ITAM motif. We observed that the upstream tyrosine plays a role in Fc gamma RIIA phagocytic signaling but is not involved in phagocytic signaling by the human gamma chain. Our data also indicate that the two ITAM tyrosines of the human gamma chain and Fc gamma RIIA do not contribute equally to Fc gamma receptor association with Syk kinase and phagocytic signaling. The data indicate that the carboxy-terminal tyrosine of the receptor cytoplasmic domain is especially important both for the interaction with Syk kinase and for phagocytosis. Elucidating such differences in gamma chain and Fc gamma RIIA signaling may be valuable in designing strategies for therapeutic intervention in hematopoietic and immunological disorders.
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Precursores Enzimáticos/fisiología , Fagocitosis/efectos de los fármacos , Proteínas Tirosina Quinasas/fisiología , Receptores de IgG/química , Animales , Células COS , Humanos , Cadenas gamma de Inmunoglobulina/inmunología , Péptidos y Proteínas de Señalización Intracelular , Pruebas de Precipitina , Transducción de Señal , Quinasa SykRESUMEN
Syk protein tyrosine kinase (PTK) is involved in signaling in leukocytes. In macrophages, Fcgamma-receptor cross-linking induces Syk PTK phosphorylation and activation, resulting in Syk-dependent events required for phagocytosis and mediator release. We hypothesized that Syk antisense oligodeoxynucleotides (ASO) delivered by aerosol to rat lungs in vivo would depress Syk PTK expression, mediator release from alveolar macrophages, and Syk-dependent pulmonary inflammation. RT-PCR and RT-in situ PCR demonstrated that aerosolized Syk ASO administration reduced Syk mRNA expression from alveolar macrophages compared with cells isolated from sham-treated rats. Western blot analysis confirmed that Syk PTK expression was reduced after Syk ASO treatment. Compared with sham-treated rats (scrambled oligodeoxynucleotide), Syk ASO treatment suppressed Fcgamma-receptor-mediated nitric oxide (86.0 +/- 8.3%) and TNF (73.1 +/- 3.1%) production by alveolar macrophages stimulated with IgG-anti-IgG complexes. In contrast, Fcgamma-receptor-induced IL-1beta release was unaffected by Syk ASO treatment. Additionally, Syk ASO suppressed Ag-induced pulmonary inflammation, suggesting that Syk ASO may prove useful as an anti-inflammatory therapy in disorders such as asthma.
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Precursores Enzimáticos/antagonistas & inhibidores , Precursores Enzimáticos/biosíntesis , Inmunosupresores/administración & dosificación , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Pulmón/patología , Macrófagos Alveolares/metabolismo , Oligonucleótidos Antisentido/administración & dosificación , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/biosíntesis , Aerosoles , Animales , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Recuento de Células/efectos de los fármacos , Precursores Enzimáticos/genética , Interleucina-1/antagonistas & inhibidores , Interleucina-1/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Pulmón/efectos de los fármacos , Pulmón/enzimología , Pulmón/inmunología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/enzimología , Macrófagos Alveolares/inmunología , Masculino , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Proteínas Tirosina Quinasas/genética , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptores de IgG/fisiología , Quinasa Syk , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/enzimología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The clinical significance of positive bacterial cultures in chronic sinusitis is often difficult to assess. Contaminants from surface colonization of the sinus mucosa may be difficult to distinguish from true intramucosal or bone involvement. Furthermore, tissue Gram stains are frequently unable to demonstrate the presence of bacteria in tissue despite endoscopic evidence of active sinusitis. In situ hybridization (ISH) techniques using bacterial rRNA probes were applied to evaluate the presence of intramucosal and intraosseous bacteria in chronic sinusitis surgical specimens. A total of 22 specimens of chronically inflamed human ethmoid bone were evaluated by ISH and by Gram stain. In three specimens, ISH identified bacterial rRNA within sinus mucosa and mucin. Notably, in these three ISH-positive specimens, Gram stain was negative in two. No specimen showed evidence of bacterial rRNA within bone. These preliminary results suggest that in situ hybridization may be a useful adjunct to current methods of detecting microorganisms within chronically infected sinus tissue.
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Hibridación in Situ/métodos , Sinusitis/diagnóstico , Adulto , Enfermedad Crónica , Humanos , Proyectos Piloto , Estudios Prospectivos , ARN Bacteriano/análisis , ARN Ribosómico/análisis , Sinusitis/microbiología , Sinusitis/cirugía , Coloración y Etiquetado/métodosRESUMEN
PURPOSE: To evaluate the effectiveness and therapeutic role of preoperative transarterial chemoembolization (TACE) of hepatoblastoma. MATERIALS AND METHODS: Four patients (one boy, three girls) with unresectable hepatoblastoma were treated twice with preoperative TACE in an effort to improve the surgical and clinical outcome. The patients ranged in age from 8 to 27 months (mean, 15 months). The first TACE was performed superselectively in tumor feeding arteries. The second TACE was performed 3 weeks later. Surgical hepatic resection was performed 1 month after the second TACE. Contrast-enhanced computed tomography (CT) was used to evaluate changes in size, volume, internal texture, and margin of the masses. The toxicity of the chemotherapeutic drugs was evaluated by blood chemistry analysis (AST/ALT, alpha-FP) performed before and after TACE, and after surgery. RESULTS: TACE allowed subsequent surgical resection in all four patients, who remained disease free 16-52 months after operation. There were no major problems related to TACE. There was no chemotherapeutic agent toxicity from TACE. The average largest diameters and volumes of the tumors decreased by 31% (8.3 to 5.6 cm) and 69% (317 to 93 cm2), respectively. CONCLUSION: TACE provided subsequent successful surgical resection and good long-term results in all four patients. The hepatoblastomas were initially considered inoperable because of extensive hepatic involvement and indistinct margins.
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Quimioembolización Terapéutica , Hepatoblastoma/terapia , Neoplasias Hepáticas/terapia , Antineoplásicos/administración & dosificación , Preescolar , Cisplatino/administración & dosificación , Medios de Contraste , Doxorrubicina/administración & dosificación , Femenino , Esponja de Gelatina Absorbible , Hepatoblastoma/diagnóstico por imagen , Hepatoblastoma/cirugía , Humanos , Lactante , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Masculino , Cuidados Preoperatorios , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Endoscopic transseptal frontal sinusotomy (TSFS) represents an alternate approach to surgical treatment of chronic frontal sinus disease that is refractory to traditional modes of medical and surgical therapy. We retrospectively reviewed our experience with endoscopic TSFS from 1995-1997. Twenty-one procedures were performed through a transseptal approach. One patient was excluded for failure to follow-up, for a total of 20 procedures. Patients were followed with serial endoscopic examinations and a telephone questionnaire with a mean follow-up of 12 months (Range 1-24 months) and 16 months (range 5-31), respectively. The primary indication for surgery was frontal recess stenosis after previous endoscopic frontal sinusotomy in 17/20 (85%). Three patients were considered poor candidates for a primary endoscopic frontal sinusotomy. Patency was maintained in all patients during the follow-up period. A diameter of greater than 3 mm was confirmed by passage of a curved suction in 19/20 (95%). Of the 19 patients that were evaluated via a telephone questionnaire, 17 patients (89.5%) reported some degree of improvement in their nasal/sinus symptoms, and 12/18 patients (67%) felt the frequency of medication requirements was less than that before undergoing endoscopic TSFS. We conclude that endoscopic TSFS represents an alternate approach to the frontal sinus that may be used by the experienced endoscopist, to augment treatment of refractory frontal sinus disease. This procedure seems especially suited for revision surgery in those patients with acquired frontal sinus stenosis. In revision operations with distorted anatomical landmarks, localization of the frontal sinus may be improved with the aid of 3-dimensional computer assisted localization systems. Unlike traditional frontal sinus obliteration, endoscopic TSFS does not preclude radiographic assessment postoperatively, and allows for endoscopic evaluation of the frontal sinus in the office setting.
Asunto(s)
Endoscopía/métodos , Seno Frontal/cirugía , Sinusitis Frontal/cirugía , Adulto , Enfermedad Crónica , Constricción Patológica/cirugía , Femenino , Estudios de Seguimiento , Seno Frontal/diagnóstico por imagen , Seno Frontal/patología , Sinusitis Frontal/diagnóstico por imagen , Sinusitis Frontal/tratamiento farmacológico , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Mucocele/cirugía , Tabique Nasal/cirugía , Enfermedades de los Senos Paranasales/cirugía , Satisfacción del Paciente , Complicaciones Posoperatorias/cirugía , Recurrencia , Reoperación , Estudios Retrospectivos , Succión/instrumentación , Terapia Asistida por Computador , Tomografía Computarizada por Rayos XRESUMEN
Endoscopic septoplasty is an attractive alternative to traditional "headlight" approaches to septoplasty. The primary advantage of the technique is the ability to reduce morbidity and postoperative swelling in isolated septal deviations by limiting the dissection to the area of the deviation. This ability to markedly reduce the extent of subperichondrial dissection is particularly valuable in patients who have undergone prior septal cartilage resection. Other advantages include improved visualization, particularly in posterior septal deformities; improved surgical transition between septoplasty and sinus surgery; and its use as an effective teaching tool. We present our experience with endoscopic septoplasty in a series of 111 patients. Surgical indications, technique, and complications are discussed.