RESUMEN
Superior repositioning of the maxilla during Le Fort I osteotomy (LFI) may narrow the inferior nasal passage. This retrospective study was performed to investigate morphological changes in the inferior nasal passage following LFI with/without additional procedures performed for nasal ventilation (horseshoe osteotomy or inferior turbinate partial resection). Three groups of patients were compared: those undergoing conventional LFI (Conv, 63 patients), LFI with horseshoe osteotomy (Hs, eight patients), and LFI with inferior turbinate partial resection (Turb, 21 patients). Coronal computed tomography images were used to evaluate the degree of stenosis of the inferior nasal passage. The soft tissue and bony tissue volumes in the inferior turbinate were also calculated three-dimensionally. The rate of obstruction of the inferior nasal passage postoperative was 65.9%, 50%, and 11.9% in the Conv, Hs, and Turb groups, respectively (Fisher's exact test, P < 0.001). Patients in the Turb group had significantly less nasal obstruction regardless of the pitch direction of the maxillary movement or volume of the bone in the inferior turbinate (all P < 0.001). In conclusion, for patients with high superior repositioning and well-developed bony tissue in the inferior turbinate, additional procedures are recommended to maintain the ventilation of the nasal passage postoperatively.
RESUMEN
In the bilateral sagittal split osteotomy, a short lingual cut is made on the medial side of the ramus; however, in some cases, a true fracture occurs on the buccal side of the ramus. The purpose of this study was to evaluate the relationship between the splitting pattern of the mandible and the form of the mandible, the surgical technique used, and the postoperative occurrence of relapse after 'unfavorable' splits. The investigation examined 143 patients in whom a short lingual cut was attempted. The rate of unfavorable split was 14.7% (42/286). A strong correlation was observed between the reach of the lateral bone cut to the inferior border of the mandible and an unfavorable split. According to multivariate regression, the factors leading to an insufficient lateral bone cut were the degree of inward curvature of the ramus (P=0.001) and the position of the lateral bone cut (P=0.002). There was no significant difference in relapse between cases of unfavorable and normal splits. An unfavorable split does not affect the prognosis of the occlusion, but it is important to confirm the inward curvature of the ramus and set the position of the lateral bone cut adequately to avoid unfavorable splits.
Asunto(s)
Mandíbula , Osteotomía Sagital de Rama Mandibular , Humanos , Mandíbula/cirugía , LenguaRESUMEN
BACKGROUND: A nomogram is progressively being used as a useful predictive tool for cancer prognosis. A nomogram to predict survival in nonresectable pancreatic cancer treated with chemotherapy has not been reported. METHODS: Using prospectively collected data on patients with nonresectable pancreatic cancer receiving gemcitabine-based chemotherapy at five Japanese hospitals, we derived a predictive nomogram and internally validated it using a concordance index and calibration plots. RESULTS: In total, 531 patients were included between June 2001 and February 2013. The American Joint Committee on Cancer (AJCC) TNM stages were III and IV in 204 and 327 patients, respectively. The median survival time of the total cohort was 11.3 months. A nomogram was generated to predict survival probabilities at 6, 12, and 18 months and median survival time, based on the following six variables: age; sex; performance status; tumour size; regional lymph node metastasis; and distant metastasis. The concordance index of the present nomogram was higher than that of the AJCC TNM staging system at 12 months (0.686 vs 0.612). The calibration plots demonstrated good fitness of the nomogram for survival prediction. CONCLUSIONS: The present nomogram can provide valuable information for tailored decision-making early after the diagnosis of nonresectable pancreatic cancer.
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Desoxicitidina/análogos & derivados , Nomogramas , Neoplasias Pancreáticas/tratamiento farmacológico , Pronóstico , Adulto , Anciano , Anciano de 80 o más Años , Desoxicitidina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Resultado del Tratamiento , GemcitabinaAsunto(s)
Remoción de Dispositivos/métodos , Cuerpos Extraños/cirugía , Gastroscopía/métodos , Páncreas/cirugía , Stents , Enfermedad Crónica , Falla de Equipo , Femenino , Migración de Cuerpo Extraño/cirugía , Gastroscopía/instrumentación , Humanos , Persona de Mediana Edad , Conductos Pancreáticos , Pancreatitis Crónica/terapiaAsunto(s)
Carcinoma Hepatocelular/complicaciones , Enfermedades del Conducto Colédoco/diagnóstico , Cálculos Biliares/diagnóstico , Neoplasias Hepáticas/complicaciones , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Enfermedades del Conducto Colédoco/etiología , Diagnóstico Diferencial , Aceite Etiodizado/administración & dosificación , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana EdadAsunto(s)
Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Biopsia con Aguja Fina/efectos adversos , Colangiocarcinoma/patología , Hemobilia/etiología , Ultrasonografía Intervencional/efectos adversos , Anciano , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Drenaje , Hemobilia/terapia , Humanos , MasculinoRESUMEN
We investigated the role of protein kinase C (PKC) in insulin-induced c-Jun N-terminal kinase (JNK) activation in rat 1 fibroblasts expressing human insulin receptors. Insulin treatment led to increased SAPK/ERK kinase 1 (SEK1) phosphorylation, and then stimulated JNK activity in a dose- and time-dependent manner, as measured either by a solid-phase kinase assay using glutathione S-transferase (GST)-c-Jun fusion protein as a substrate, or by quantitation of the levels of phosphorylated JNK by Western blotting using anti-phospho-JNK antibody. Insulin-induced JNK activation was potentiated by either preincubating cells with 2 nM GF109203X (PKC inhibitor) or down-regulation of PKC by overnight treatment with 100 nM tetradecanoyl phorbol acetate. In contrast, brief preincubation with 100 nM tetradecanoyl phorbol acetate inhibited the insulin- induced JNK activation. Furthermore, we found that 5 microM rottlerin, a PKCdelta inhibitor, enhanced insulin-induced JNK activation, but a PKCbeta inhibitor, LY333531, had no effect. Consistent with these findings, overexpression of PKCdelta led to decreased insulin-induced JNK activation, whereas overexpression of PKCbeta had no effect. Although overexpression of wild-type PKCdelta attenuated insulin-induced JNK activation, a kinase-dead PKCdelta mutant did not cause such attenuation. Finally, we found that the magnitude of insulin-induced JNK activation was inversely correlated with the expression level of PKCdelta among different cell lines. In conclusion, the expression of PKCdelta may negatively regulate insulin-induced JNK activation.
Asunto(s)
Proteínas de Ciclo Celular , Insulina/farmacología , Isoenzimas/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos , MAP Quinasa Quinasa 4 , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Fosfoproteínas Fosfatasas , Proteína Quinasa C/farmacología , Acetofenonas/farmacología , Animales , Benzopiranos/farmacología , Línea Celular , Fosfatasa 1 de Especificidad Dual , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Fibroblastos/enzimología , Expresión Génica , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Humanos , Proteínas Inmediatas-Precoces/metabolismo , Isoenzimas/antagonistas & inhibidores , Isoenzimas/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Fosforilación , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/genética , Proteína Fosfatasa 1 , Proteínas Tirosina Fosfatasas/metabolismo , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Proto-Oncogénicas c-jun/metabolismo , Ratas , Receptor de Insulina/genética , Proteínas Recombinantes de Fusión/metabolismo , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
Fibroblastic proliferation accompanies many angiogenesis-related retinal and systemic diseases. Since connective tissue growth factor (CTGF) is a potent mitogen for fibrosis, extracellular matrix production, and angiogenesis, we have studied the effects and mechanism by which vascular endothelial growth factor (VEGF) regulates CTGF gene expression in retinal capillary cells. In our study, VEGF increased CTGF mRNA levels in a time- and concentration-dependent manner in bovine retinal endothelial cells and pericytes, without the need of new protein synthesis and without altering mRNA stability. VEGF activated the tyrosine receptor phosphorylation of KDR and Flt1 and increased the binding of phosphatidylinositol 3-kinase (PI3-kinase) p85 subunit to KDR and Flt1, both of which could mediate CTGF gene induction. VEGF-induced CTGF expression was mediated primarily by PI3-kinase activation, whereas PKC and ERK pathways made only minimal contributions. Furthermore, overexpression of constitutive active Akt was sufficient to induce CTGF gene expression, and inhibition of Akt activation by overexpressing dominant negative mutant of Akt abolished the VEGF-induced CTGF expression. These data suggest that VEGF can increase CTGF gene expression in bovine retinal capillary cells via KDR or Flt receptors and the activation of PI3-kinase-Akt pathway independently of PKC or Ras-ERK pathway, possibly inducing the fibrosis observed in retinal neovascular diseases.
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Factores de Crecimiento Endotelial/farmacología , Endotelio Vascular/metabolismo , Sustancias de Crecimiento/biosíntesis , Proteínas Inmediatas-Precoces/biosíntesis , Péptidos y Proteínas de Señalización Intercelular , Linfocinas/farmacología , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas/fisiología , Proteínas Tirosina Quinasas Receptoras/fisiología , Receptores de Factores de Crecimiento/fisiología , Retina/metabolismo , Animales , Bovinos , Células Cultivadas , Factor de Crecimiento del Tejido Conjuntivo , Cicloheximida/farmacología , Sustancias de Crecimiento/genética , Proteínas Inmediatas-Precoces/genética , Isoenzimas/fisiología , Fosforilación , Proteína Quinasa C/fisiología , Proteínas Proto-Oncogénicas c-akt , ARN Mensajero/análisis , Receptores de Factores de Crecimiento Endotelial Vascular , Factor A de Crecimiento Endotelial Vascular , Receptor 1 de Factores de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.
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Endotelina-1/genética , Endotelio Vascular/fisiología , Glucosa/farmacología , Proteína Quinasa C/metabolismo , Vasos Retinianos , Transcripción Genética/efectos de los fármacos , Animales , Capilares , Bovinos , Células Cultivadas , Endotelio Vascular/efectos de los fármacos , Activación Enzimática , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Indoles/farmacología , Isoenzimas/metabolismo , Maleimidas/farmacología , Pericitos/efectos de los fármacos , Pericitos/fisiología , Proteína Quinasa C beta , Proteína Quinasa C-alfa , Proteína Quinasa C-delta , ARN Mensajero/genéticaRESUMEN
PURPOSE: Hepatocyte growth factor (HGF), also called scatter factor, stimulates growth and motility in nonocular endothelial cells and smooth muscle cells through its receptor c-Met. Recent reports suggest that HGF is increased in the serum and vitreous of patients with proliferative diabetic retinopathy and that smooth muscle cells and retinal pigment epithelial cells secrete HGF in the eye. However, little is known about HGF's action in the retina. In this study, the activity, expression, and signaling pathways of HGF were investigated in bovine retinal microvascular endothelial cells (BRECs). METHODS: Mitogenic and motogeneic effects of HGF on BRECs were examined using cell counts, thymidine uptake, and migration assays. MAP kinase (MAPK) phosphorylation was examined by Western blot analysis. Protein kinase C (PKC), MAPK, and PI3 kinase involvement were evaluated using selective inhibitors and activity assays. Expression of HGF and c-Met was evaluated by reverse transcription-polymerase chain reaction. RESULTS: HGF and c-Met were both expressed in BRECs. HGF stimulated BREC growth in a time- and dose-dependent manner, observed at HGF concentrations of 5 ng/ml or more and maximal (410%) at 100 ng/ml (P < 0.001). HGF increased BREC migration in a dose-dependent manner with a maximal 3.4-fold increase at 50 ng/ml after 5 hours. HGF induced time- and dose-dependent MAPK phosphorylation, initially evident at 5 minutes (P < 0.001) or 5 ng/ml (P < 0.050) and maximal after 15 minutes (>80-fold, P < 0.001) or 50 ng/ml (>20-fold, P < 0.001), respectively. MAPK phosphorylation was maintained for more than 2 hours. This response was inhibited 31% by 0.1 microm wortmannin and 76% by 30 microm LY294002, another PI3 kinase inhibitor. The non-isoform-selective PKC inhibitor GFX inhibited HGF-induced MAPK phosphorylation by only 15% at 5 microm. Combined PKC and PI3 kinase inhibition was additive (P < 0.05). Cell migration was inhibited 30% by wortmannin (P < 0.01) and 32% by GFX (P < 0.05), and again the effect was additive (P < 0.001). HGF-induced BREC growth was suppressed by PI3 kinase, PKC, or MAPK inhibition (all P < 0.01). HGF (50 ng/ml) stimulated PI3 kinase activity 347% (P < 0.001) and PKC activity 37% (P < 0.05). HGF-induced MAPK phosphorylation and mitogenesis were not inhibited by vascular endothelial growth factor (VEGF)-neutralizing antibody. CONCLUSIONS: HGF and its receptor are expressed in BREC, and HGF stimulates both BREC growth and migration at concentrations observed in the human eye with diabetic retinopathy. HGF signaling appears to involve activation of both PKC and PI3 kinase, inducing MAPK phosphorylation that is critical for migration and growth. However, VEGF does not appear to mediate these initial HGF effects. These results indicate that HGF could have a significant role in mediating retinal endothelial cell proliferation and migration in diabetic retinopathy, and they begin to elucidate the signal transduction pathway by which this action may occur.
Asunto(s)
División Celular/fisiología , Movimiento Celular/fisiología , Endotelio Vascular/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Vasos Retinianos/metabolismo , Transducción de Señal/fisiología , Animales , Western Blotting , Bovinos , Recuento de Células , Células Cultivadas , Relación Dosis-Respuesta a Droga , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/farmacología , Sistema de Señalización de MAP Quinasas/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteína Quinasa C/metabolismo , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , ARN Mensajero/metabolismo , Vasos Retinianos/citología , Vasos Retinianos/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Previously, we have reported that the lipoprotein fraction containing intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) isolated from diabetics stimulates an atherogenic cytokine in cultured endothelial cells. To study which lipoprotein fraction isolated from diabetics can modulate the gene expression in endothelial cells, we isolated IDL and LDL fractions from 14 type 2 diabetics and seven age- and BMI- adjusted non-diabetics. We measured the effects of the lipoproteins on mRNA expression of atherogenic molecules in cultured endothelial cells. We found that the IDL fraction stimulated monocyte chemoattractant protein-1 (MCP-1) mRNA expression in endothelial cells as time- and dose-dependent fashions, while the LDL fraction was not effective. IDL isolated from diabetics also increased not only platelet-derived growth factor B-chain, but also intercellular adhesion molecule-1 mRNA contents. Furthermore, the HbA(1c) levels in diabetics were significantly correlated with their abilities of IDL to increase MCP-1 mRNA content in the cells and the increment coincided with the increase in MCP-1 protein release into culture media. These results indicate that qualitative as well as quantitative changes in IDL fraction in diabetes are atherogenic through stimulating gene expression of atherogenic molecules in endothelial cells.
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Quimiocina CCL2/genética , Diabetes Mellitus Tipo 2/sangre , Endotelio Vascular/metabolismo , Regulación de la Expresión Génica/fisiología , Molécula 1 de Adhesión Intercelular/genética , Lipoproteínas/sangre , Lipoproteínas/farmacología , Factor de Crecimiento Derivado de Plaquetas/genética , Transcripción Genética , Arteriosclerosis , Células Cultivadas , Colesterol/sangre , Femenino , Humanos , Lipoproteínas/aislamiento & purificación , Lipoproteínas IDL , Lipoproteínas LDL/sangre , Lipoproteínas LDL/aislamiento & purificación , Lipoproteínas LDL/farmacología , Masculino , Persona de Mediana Edad , ARN Mensajero , Valores de Referencia , Triglicéridos/sangre , Venas UmbilicalesRESUMEN
BACKGROUND: The vasodilatory effect of insulin can be acute or increase with time from 1 to 7 hours, suggesting that insulin may enhance the expression of endothelial nitric oxide synthase (eNOS) in endothelial cells. The objective of the present study was to characterize the extent and signaling pathways by which insulin regulates the expression of eNOS in endothelial cells and vascular tissues. METHODS AND RESULTS: Physiological concentrations of insulin (10(-10) to 10(-7) mmol/L) increased the levels of eNOS mRNA, protein, and activity by 2-fold after 2 to 8 hours of incubation in cultured bovine aortic endothelial cells. Insulin enhanced eNOS gene expression in microvessels isolated from Zucker lean rats but not from insulin-resistant Zucker fatty rats. Inhibitors of phosphatidylinositol-3 kinase (PI-3 kinase) decreased the effect of insulin on eNOS gene expression, but a general protein kinase C (PKC) inhibitor, GF109203X or PKCbeta isoform inhibitor, LY333531 enhanced eNOS expression. In contrast, PKC activators inhibited both the activation by insulin of PI-3 kinase and eNOS mRNA levels. Overexpression of PKCbeta isoform in endothelial cells inhibited the stimulation by insulin of eNOS expression and PI-3 kinase activities in parallel. CONCLUSIONS: Insulin can regulate the expression of eNOS gene, mediated by the activation of PI-3 kinase, in endothelial cells and microvessels. Thus, insulin may chronically modulate vascular tone. The activation of PKC in the vascular tissues as in insulin resistance and diabetes may inhibit PI-3 kinase activity and eNOS expression and may lead to endothelial dysfunctions in these pathological states.
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Endotelio Vascular/enzimología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hipoglucemiantes/farmacología , Insulina/farmacología , Óxido Nítrico Sintasa/biosíntesis , Animales , Bovinos , Células Cultivadas , Diabetes Mellitus/enzimología , Inhibidores Enzimáticos/farmacología , Indoles/farmacología , Maleimidas/farmacología , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo III , Fosfatidilinositol 3-Quinasas/metabolismo , Proteína Quinasa C/metabolismo , Ratas , Ratas Zucker , Transducción de Señal/efectos de los fármacosRESUMEN
Elevated levels of glycocojugates, commonly observed in the myocardium of diabetic animals and patients, are postulated to contribute to the myocardial dysfunction in diabetes. Previously, we reported that UDP-GlcNAc: Galbeta1-3GalNAcalphaRbeta1-6-N-acetylglucosaminyltransferas e (core 2 GlcNAc-T), a developmentally regulated enzyme of O-linked glycans biosynthesis pathway, is specifically increased in the heart of diabetic animals and is regulated by hyperglycemia and insulin. In this study, transgenic mice overexpressing core 2 GlcNAc-T with severe increase in cardiac core 2 GlcNAc-T activities were normal at birth but showed progressive and significant cardiac hypertrophy at 6 months of age. The heart of transgenic mice showed elevation of sialylated O-glycan and increases of c-fos gene expression and AP-1 activity, which are characteristics of cardiac stress. Furthermore, transfection of PC12 cells with core 2 GlcNAc-T also induced c-fos promoter activation, mitogen activated-protein kinase (MAPK) phosphorylation, Trk receptor glycosylation, and cell differentiation. These results suggested a novel role for core 2 GlcNAc-T in the development of diabetic cardiomyopathy and modulation of the MAP kinase pathway in the heart.-Koya, D., Dennis, J. W., Warren, C. E., Takahara, N., Schoen, F. J., Nishio, Y., Nakajima, T., Lipes, M. A., King, G. L. Overexpression of core 2 N-acetylglycosaminyltransferase enhances cytokine actions and induces hypertrophic myocardium in transgenic mice.
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Cardiomegalia/etiología , Citocinas/fisiología , Miocardio/metabolismo , N-Acetilglucosaminiltransferasas/fisiología , Animales , Cardiomegalia/enzimología , Cardiomegalia/metabolismo , Glicosilación , Ratones , Ratones Transgénicos , Miocardio/enzimología , N-Acetilglucosaminiltransferasas/biosíntesis , Células PC12 , Polisacáridos/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Receptor trkA/metabolismo , Transducción de Señal , Factor de Transcripción AP-1/metabolismo , TransfecciónRESUMEN
Hyperglycemia can cause vascular dysfunctions by multiple factors including hyperosmolarity, oxidant formation, and protein kinase C (PKC) activation. We have characterized the effect of hyperglycemia on p38 mitogen-activated protein (p38) kinase activation, which can be induced by oxidants, hyperosmolarity, and proinflammatory cytokines, leading to apoptosis, cell growth, and gene regulation. Glucose at 16.5 mM increased p38 kinase activity in a time-dependent manner compared with 5.5 mM in rat aortic smooth muscle cells (SMC). Mannitol activated p38 kinase only at or greater than 22 mM. High glucose levels and a PKC agonist activated p38 kinase, and a PKC inhibitor, GF109203X, prevented its activation. However, p38 kinase activation by mannitol or tumor necrosis factor-alpha was not inhibited by GF109203X. Changes in PKC isoform distribution after exposure to 16.5 mM glucose in SMC suggested that both PKC-beta2 and PKC-delta isoforms were increased. Activities of p38 kinase in PKC-delta- but not PKC-beta1-overexpressed SMC were increased compared with control cells. Activation of p38 kinase was also observed and characterized in various vascular cells in culture and aorta from diabetic rats. Thus, moderate hyperglycemia can activate p38 kinase by a PKC-delta isoform-dependent pathway, but glucose at extremely elevated levels can also activate p38 kinase by hyperosmolarity via a PKC-independent pathway.
Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Activación Enzimática/efectos de los fármacos , Glucosa/farmacología , Proteínas Quinasas Activadas por Mitógenos , Músculo Liso Vascular/enzimología , Adenoviridae/genética , Animales , Células Cultivadas , Humanos , Hiperglucemia/fisiopatología , Imidazoles/farmacología , Indoles/farmacología , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Masculino , Maleimidas/farmacología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Concentración Osmolar , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , Proteína Quinasa C beta , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/farmacología , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
This paper describes a rare case of biliary atresia (BA) in which massive postoperative bleeding developed due to portal hypertensive enteropathy. A 15-year-old boy had been doing well after Kasai's operation for BA. At around the age of 6 years he developed recurrent episodes of esophageal variceal bleeding and underwent esophageal transection, splenectomy, sclerotherapy, and embolization of the left gastric vein. At the age of 15 years he suddenly developed abdominal pain, hematemesis, and massive tarry stools. His hemoglobin level was 6.3 g/dl. Endoscopy showed several small, polypoid lesions in the jejunum beyond Treitz' ligament. The source of the bleeding was one of these lesions located in the proximal jejunojejunostomy of the Roux-en-Y loop. Because he had repeated episodes of melena, he underwent partial resection of the jejunum under endoscopic guidance. He has since been free of gastrointestinal (GI) bleeding. From this experience, we conclude that the polypoid lesions of an enteropathy may be a cause of massive GI bleeding in the postoperative portal hypertension of BA.
Asunto(s)
Atresia Biliar/cirugía , Hemorragia Gastrointestinal/etiología , Hipertensión Portal/complicaciones , Hemorragia Posoperatoria/etiología , Adolescente , Atresia Biliar/complicaciones , Hemorragia Gastrointestinal/cirugía , Humanos , Masculino , Hemorragia Posoperatoria/cirugíaRESUMEN
BACKGROUND: In order to characterize the diversity of Helicobacter pylori (H. pylori) in infected individuals, 10 colonies of H. pylori were isolated from the gastric juice of 25 patients with gastroduodenal diseases (total 250 isolates). METHODS: Protein profiles of isolates were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Results were confirmed by Western blotting (immunoblotting) test using rabbit antisera against three different strains of H. pylori. RESULTS: The protein profiles of 18 of 25 cases (72%) showed a single type of H. pylori with the same polypeptide pattern. In contrast, heterogeneity in the protein profiles was seen in isolates from seven cases (28%). Two differing H. pylori types with two very different polypeptide patterns were found in 10 isolates from one case. In six patients, the protein profiles of isolates were found to have variations in their polypeptides between molecular weights of 30,000 (30K) and 14K, which are thought to be associated with bacterial membrane protein. In some isolates, a polypeptide band of the 16K was missing. Each of three different antisera confirmed differences among the distinct isolates from individual patients. CONCLUSIONS: These findings suggest that more than one antigenically different strain of H. pylori may exist in same infected individuals.