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1.
Clin Radiol ; 75(11): 879.e1-879.e6, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32727657

RESUMEN

AIM: To evaluate the technical feasibility and safety of percutaneous recanalisation of benign postoperative hepaticojejunostomy strictures using the reverse end of a microwire. MATERIALS AND METHODS: Twenty-one patients with benign postoperative hepaticojejunostomy strictures that had failed to recanalise following management with conventional percutaneous techniques from January 2012 to March 2019 were included in the study. The stricture was punctured by the reverse end of a microwire. Subsequently, serial balloon dilatation and covered stent placement was performed. Technical as well as clinical success, complications, and patency of the hepaticojejunostomy were evaluated. RESULTS: Technical success was achieved in 19 of 21 (90.5%) patients. The mean number of treatment sessions was 1.2 (range, 1-2). The obstructive symptoms were resolved within 3 days after the procedure in 19 patients (100%). There were no major complications. The 1-year and 3-year patency rates were 76.9% and 61.5%, respectively. CONCLUSION: Percutaneous recanalisation using the reverse end of a microwire is technically feasible and safe in the treatment of benign postoperative hepaticojejunostomy strictures. This technique is useful when the conventional percutaneous technique cannot be used to cross the stricture.


Asunto(s)
Constricción Patológica/etiología , Enfermedades del Yeyuno/etiología , Yeyuno/diagnóstico por imagen , Yeyuno/cirugía , Hepatopatías/etiología , Hígado/cirugía , Páncreas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/cirugía , Femenino , Humanos , Enfermedades del Yeyuno/diagnóstico por imagen , Enfermedades del Yeyuno/cirugía , Hígado/diagnóstico por imagen , Hepatopatías/diagnóstico por imagen , Hepatopatías/cirugía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
2.
Clin Radiol ; 73(4): 412.e9-412.e16, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29203094

RESUMEN

AIM: To compare the clinical effectiveness of percutaneous stent placement between T and criss-cross configuration techniques in patients with advanced malignant hilar biliary obstruction. MATERIALS AND METHODS: Between January 2009 and December 2014, 59 patients who underwent percutaneous stent placement for malignant hilar obstruction were included in this retrospective study. T-configured stent placement (T group) was performed in 33 patients and criss-cross configured stent placement (criss-cross group) in 26 patients. Technical and clinical success, complications, patient survival, and stent patency were compared between the two groups. RESULTS: Stent placement was technically successful in all patients of the two groups. Clinical success was achieved in 30 (90.9%) patients of T group and 25 (96.9%) of criss-cross group (p=0.62). Two patients in the T group (6.1%) required additional stent placement for internal drainage of undrained sector. There were no major complications. Median survival was not statistically different between the two groups (128 days in the T group versus 183 days in the criss-cross group; p=0.33). Stent occlusion occurred in 15 patients in the T group and seven patients in the criss-cross group. The stent patency of the criss-cross group (median 330 days) was longer than that of the T group (median 132 days; p=0.0007). CONCLUSIONS: Early clinical effectiveness is comparable between the two techniques; however, additional intervention is occasionally required for drainage of an undrained sector after T-configured stent placement. Stent placement with criss-cross configuration provides longer stent patency than T-configuration technique.


Asunto(s)
Neoplasias de los Conductos Biliares/complicaciones , Colestasis/etiología , Colestasis/terapia , Tumor de Klatskin/complicaciones , Cuidados Paliativos/métodos , Stents , Anciano , Conductos Biliares/diagnóstico por imagen , Pancreatocolangiografía por Resonancia Magnética , Colestasis/diagnóstico por imagen , Drenaje/métodos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
3.
Clin Radiol ; 70(9): 1009-15, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26126713

RESUMEN

AIM: To compare the therapeutic efficacy of fluoroscopy-guided radiofrequency ablation (F-RFA) and ultrasound-guided RFA (US-RFA) in treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between January 2006 and January 2012, 93 patients with small HCCs underwent percutaneous RFA. In 42 patients with 46 HCCs invisible on US, F-RFA was performed following intra-arterial iodised oil injection (group A). The remaining 51 patients with 58 HCCs received US-RFA (group B). Technical effectiveness, complications, local tumour progression, and patient survival were retrospectively compared between the two groups. RESULTS: Technical effectiveness was achieved in 45 HCCs of group A (97.8%) and 64 HCCs of group B (96.6%; p=0.65). There was no major complication in either group. The 1-, 3-, and 5-year local tumour progression rates were lower in group A than those of group B with marginal significance (0%, 3.7% and 3.7% in group A, and 13%, 13%, and 13% in group B; p=0.05). The 1-, 3-, and 5-year patient survival rates were 100%, 58.3%, and 51.2% (group A), and 82.4%, 54.9%, and 46.1% (group B; p=0.26). CONCLUSIONS: F-RFA is a feasible and safe treatment for small HCC invisible on US. Its therapeutic efficacy was comparable with that of US-RFA.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Radiografía Intervencional , Ultrasonografía Intervencional , Anciano , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/diagnóstico por imagen , Ablación por Catéter , Medios de Contraste/administración & dosificación , Progresión de la Enfermedad , Aceite Etiodizado/administración & dosificación , Femenino , Fluoroscopía , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia
4.
Phys Rev Lett ; 111(13): 132504, 2013 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-24116774

RESUMEN

A measurement of beam helicity asymmetries in the reaction 3He[over →](e[over →],e'n)pp is performed at the Mainz Microtron in quasielastic kinematics to determine the electric to magnetic form factor ratio of the neutron GEn/GMn at a four-momentum transfer Q2=1.58 GeV2. Longitudinally polarized electrons are scattered on a highly polarized 3He gas target. The scattered electrons are detected with a high-resolution magnetic spectrometer, and the ejected neutrons are detected with a dedicated neutron detector composed of scintillator bars. To reduce systematic errors, data are taken for four different target polarization orientations allowing the determination of GEn/GMn from a double ratio. We find µnGEn/GMn=0.250±0.058(stat)±0.017(syst).

5.
Phys Biol ; 8(1): 015008, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21301062

RESUMEN

Increased stiffness represents a hallmark of breast cancer that has been attributed to the altered physicochemical properties of the extracellular matrix (ECM). However, the role of fibronectin (Fn) in modulating the composition and mechanical properties of the tumor-associated ECM remains unclear. We have utilized a combination of biochemical and physical science tools to evaluate whether paracrine signaling between breast cancer cells and adipose progenitor cells regulates Fn matrix assembly and stiffness enhancement in the tumor stroma. In particular, we utilized fluorescence resonance energy transfer imaging to map the molecular conformation and stiffness of Fn that has been assembled by 3T3-L1 preadipocytes in response to conditioned media from MDA-MB231 breast cancer cells. Our results reveal that soluble factors secreted by tumor cells promote Fn expression, unfolding, and stiffening by adipose progenitor cells and that transforming growth factor-ß serves as a soluble cue underlying these changes. In vivo experiments using orthotopic co-transplantation of primary human adipose-derived stem cells and MDA-MB231 into SCID mice support the pathological relevance of our results. Insights gained by these studies advance our understanding of the role of Fn in mammary tumorigenesis and may ultimately lead to improved anti-cancer therapies.


Asunto(s)
Tejido Adiposo/citología , Neoplasias de la Mama/metabolismo , Fibronectinas/metabolismo , Transferencia Resonante de Energía de Fluorescencia/métodos , Células Madre/metabolismo , Células 3T3 , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Células Cultivadas , Femenino , Fibronectinas/ultraestructura , Humanos , Ratones , Ratones SCID , Células Madre/patología , Factor de Crecimiento Transformador beta/metabolismo
6.
Endoscopy ; 39(5): 448-54, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17516352

RESUMEN

BACKGROUND AND STUDY AIMS: It is known that metal stent placement is safe, easy, and effective for the treatment of malignant colorectal obstruction, but these stents are associated with delayed complications of tumor ingrowth and stent migration. The aim of this study was to prospectively investigate the technical feasibility, clinical effectiveness, and safety of a dual-design colorectal stent (consisting of an outer stent and an inner bare nitinol stent) in patients with malignant colorectal obstruction. PATIENTS AND METHODS: Placement of the dual stent using a 4.5-mm stent delivery system was attempted in 151 patients with malignant colorectal obstruction, either before surgery (n = 50) or for palliation (n = 101). Multivariate logistic regression analysis was used to identify risk factors associated with complications. RESULTS: Stent placement was technically successful in 145/151 patients (96%). Of the patients who had a technically successful placement, bowel obstruction resolved within 2 days after stent placement in 48/50 (96%) of the patients in the bridge-to-surgery group and in 87/95 (92%) of the patients in the palliative group. Perforation occurred in 16 patients, incomplete stent expansion in eight patients, stent migration in four patients, tumor overgrowth in five patients, severe rectal pain in five patients, and bleeding in eight patients. Complete obstruction was the only significant risk factor for perforation (odds ratio 6.88, 95% CI 2.04-23.17, P = 0.002). In the palliative group, the median survival was 152.0 days and the mean survival was 263.8 days. CONCLUSIONS: The dual stent with a 4.5-mm stent delivery system is easy to insert, safe, and reasonably effective for the palliative treatment of malignant colorectal obstruction. However, a great deal of care is needed in its deployment because of the high rate of perforation.


Asunto(s)
Neoplasias Colorrectales/complicaciones , Obstrucción Intestinal/terapia , Stents , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diseño de Equipo , Femenino , Estudios de Seguimiento , Migración de Cuerpo Extraño/etiología , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/mortalidad , Perforación Intestinal/etiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Dolor/etiología , Cuidados Paliativos , Estudios Prospectivos , Stents/efectos adversos , Tasa de Supervivencia
7.
Eur J Radiol ; 39(3): 163-7, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11566243

RESUMEN

A case of tuberculous dactylitis in an immunocompetent patient is presented and the radiographic findings and differential diagnosis discussed. MR image, although nonspecific, was helpful for differential diagnosis and evaluating the extent of the lesion. Although this is a rare condition, the diagnosis should be considered when dealing with an unusual destructive bony lesion.


Asunto(s)
Imagen por Resonancia Magnética , Tuberculosis Osteoarticular/diagnóstico , Adolescente , Diagnóstico Diferencial , Dedos , Humanos , Masculino
8.
Korean J Radiol ; 2(3): 145-50, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11752985

RESUMEN

OBJECTIVE: To investigate the effectiveness of the newly designed Niti-S stent in the management of iliac arterial stenoses and occlusions. MATERIALS AND METHODS: Stenoses (n=25) or occlusions (n=5) in the iliac arteries of 25 patients (30 limbs) were treated. The site of the lesions was the common (n=15) or external (n=11) iliac artery, or both (n=4). Eight limbs were treated for diffuse disease, six for highly eccentric lesion, five for occlusive lesion, and 11 for failed angioplasty. RESULTS: In all patients, technical success was achieved without major complications. One death, not procedure-related, occurred within 30 days. Ankle-brachial indexes improved from 0.63 +/- 0.30 to 0.99 +/- 0.21, and ischemic symptoms showed improvement in 22 patients (88%). Fontaine classifications before stenting, namely IIa(n=3), IIb(n=16), III(n=2), and IV(n=4) improved to I(n=17), IIa(n=5), and IV(n=3). Follow-up over a 27 (mean, 19.8 +/- 8)-month period showed that cumulative patency rates were 95.8% at 1 year and 86.2% at 2 and 3 years. No significant decrease in the mean ankle-brachial index was observed. CONCLUSION: The Niti-S stent appears to be a safe and effective device for the treatment of iliac stenoses and occlusions. These preliminary results require confirmation with a larger series.


Asunto(s)
Aleaciones , Arteriopatías Oclusivas/terapia , Arteria Ilíaca , Stents , Anciano , Diseño de Equipo , Femenino , Humanos , Masculino
9.
Int J Artif Organs ; 23(9): 624-8, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11059885

RESUMEN

BACKGROUND: A precondition for the successful formation of tissue-engineered heart valves is the generation of a proper matrix on biodegradable scaffolds over a limited period of time. The aim of this study was to find an effective method of seeding autologous cells on these scaffolds to create a new matrix for heart valves. METHODS: Myofibroblasts and endothelial cells were isolated and cultured from an ovine artery. A synthetic biodegradable scaffold consisting of polyglycolic and polylactic acids was seeded first with the myofibroblasts, then coated with endothelial cells. Three different methods of myofibroblast seeding were compared: I) daily seeding of myofibroblasts (1x10(6)) for ten days and culture for four days; II) seeding of myofibroblasts (1x10(7)) and culture for 14 days with the use of a simple medium; III) seeding of myofibroblasts (1x10(7)) with the use of a medium containing collagen and culture for 14 days. Light and electron microscopic analyses were performed. RESULTS: The group that used the medium containing collagen showed the best results in terms of seeding efficiency. CONCLUSION: Seeding autologous cells with a medium containing collagen onto the scaffold showed the largest cell population and might generate the best matrix on the scaffold.


Asunto(s)
Órganos Bioartificiales , Endotelio Vascular/citología , Prótesis Valvulares Cardíacas , Músculo Liso Vascular/citología , Implantes Absorbibles , Animales , Células Cultivadas , Arteria Femoral , Fibroblastos , Ácido Láctico , Ensayo de Materiales , Poliésteres , Ácido Poliglicólico , Polímeros , Diseño de Prótesis , Ovinos
10.
Rhinology ; 33(4): 189-93, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8919209

RESUMEN

Primary ciliary dyskinesia is a genetically determined disorder characterized by immotility or poor motility of the cilia in the airways and elsewhere. Certain specific defects in the ciliary axoneme can be found, which are pathognomonic of the syndrome. The defects include missing dynein arms, abnormally short dynein arms, spokes with no central sheath, missing central microtubules, and displacement of one of the nine peripheral doublets. We have reviewed 19 cases of primary ciliary dyskinesia diagnosed by transmission and scanning electron microscopy. The age distribution ranged from five to 15 years, and there were six males and 13 females. All 19 cases had abnormal cilia which consisted of Ia (three cases), Ib (three cases), isolated Id (three cases), isolated II (one case), isolated III (two cases), and Id + other types (seven cases), according to Sturgess' classification. The most pronounced clinical manifestations are chronic paranasal sinusitis (52%) and chronic bronchiectasis (52%), followed by bronchopneumonia (26%), chronic bronchitis (21%), and nasal polyps (15%).


Asunto(s)
Trastornos de la Motilidad Ciliar/patología , Mucosa Nasal/ultraestructura , Adolescente , Niño , Preescolar , Cilios/ultraestructura , Femenino , Humanos , Masculino , Microscopía Electrónica
11.
Int J Tuberc Lung Dis ; 11(7): 781-7, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17609054

RESUMEN

OBJECTIVE: To evaluate the factors that influence the outcome of bronchial arterial embolisation (BAE) in chronic tuberculosis (TB). In cases of chronic TB, non-bronchial systemic arteries (NBSA) provide a significant source of massive or recurrent haemoptysis. DESIGN: Medical records and radiological findings of 30 consecutive TB patients who underwent BAE were retrospectively analysed and compared with those of 19 bronchiectasis patients. RESULTS: Chronic TB patients had higher numbers of total feeding vessels (4.40 + or - 3.85 vs. 1.79 + or - 1.51, P = 0.007) and NBSA (1.57 + or - 1.63 vs. 0.42 + or - 0.61, P = 0.005) than the bronchiectasis patients. The number of embolisations required for obliterating feeding vessels (3.87 + or - 2.48 vs. 1.95 + or - 1.47, P = 0.004), and the incidence of incomplete embolisation (30% vs. 5.3%, P = 0.033) were also higher in the TB patients. Moreover, recurrence after BAE was more frequent in the TB patients (17/30, 56.7% vs. 5/19, 26.3%, P = 0.037). Male sex, past history of haemoptysis and incomplete embolisation during BAE were associated with higher recurrence of haemoptysis in chronic TB patients. The existence of a fungus ball or significant pleural thickening (> or =10 mm) was not found to influence the recurrence rate of haemoptysis. CONCLUSION: The haemoptysis recurrence rate was higher in chronic TB than in bronchiectasis; this was found to be related to incomplete feeding vessel embolisation.


Asunto(s)
Arterias Bronquiales , Bronquiectasia/complicaciones , Embolización Terapéutica/métodos , Hemoptisis/etiología , Hemoptisis/terapia , Tuberculosis Pulmonar/complicaciones , Adulto , Anciano , Angiografía , Bronquiectasia/diagnóstico , Enfermedad Crónica , Estudios de Cohortes , Intervalos de Confianza , Embolización Terapéutica/efectos adversos , Femenino , Estudios de Seguimiento , Hemoptisis/epidemiología , Hemoptisis/fisiopatología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Probabilidad , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Tuberculosis Pulmonar/diagnóstico
12.
Artif Organs ; 22(10): 892-7, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9790089

RESUMEN

Tubing wear and spallation have long been recognized as complications of roller pumps used in cardiopulmonary bypass (CPB) although the reported results of studies of polyvinylchloride (PVC) and silicone rubber tubing wear are still controversial. We conducted phase-contrast microscope (PCM) and scanning electron microscope (SEM) studies of roller pump induced tubing wear. A closed CPB circuit was constructed, and both PVC and silicone rubber tubing (1/2 inch internal diameter [ID]) were tested under normal and tight occlusions of a dual roller pump at a typical CPB flow rate (4,500 ml/min) for 1, 2, 4, and 6 h in quintet. After each pump run, the tubing was removed. It was first examined with PCM, and suspicious portions were then analyzed in detail using SEM. In silicone rubber tubing of longer running time, the external diameter often decreased. Wear was invariably found on the luminal surfaces at the junction of the inner and outer walls of both the PVC and silicone rubber tubing with no significant differences between normal and tight occlusion. The grooves in the PVC tubing were narrow and continuous with occasional deep cracks in the tubing after more than 3 h of pump run. The grooves in the silicone rubber tubing were wide and often interrupted with occasional V-shaped elevated areas. Craters of less than 50 microns occurred sporadically in both types of tubing. Neither PVC nor silicone rubber tubing offers advantages in terms of roller pump induced tubing wear and spallation.


Asunto(s)
Puente Cardiopulmonar/instrumentación , Intubación/instrumentación , Cloruro de Polivinilo , Elastómeros de Silicona , Humanos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Microscopía de Contraste de Fase , Cloruro de Polivinilo/química , Reología , Elastómeros de Silicona/química , Propiedades de Superficie , Factores de Tiempo
13.
Artif Organs ; 24(11): 874-8, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11119075

RESUMEN

The clinical value of arterial line filters is still a controversial issue. Proponents of arterial line filtration argue that filters remove particulate matter and undissolved gas from circulation while opponents argue the absence of conclusive clinical data. We conducted scanning electron microscope (SEM) studies of arterial line filters used clinically in the cardiopulmonary bypass circuits during adult cardiac surgery and analyzed the types and characteristics of materials entrapped in the arterial line filters. Twelve arterial line filters were obtained during routine hypothermic cardiopulmonary bypass in 12 adult cardiac patients. The arterial line filter was a screen type with a pore size of 40 microm (Baxter Health Care Corporation, Bentley Division, Irvine, CA, U.S.A. ). After opening the housing, the woven polyester strands were examined with SEM. All segments examined (120 segments, each 2.5 x 2. 5 cm) contained no embolic particles larger in their cross-sectional area than the pore size of the filter (40 microm). The origins of embolic particulates were mostly from environmental foreign bodies. This may suggest a possible need for more aggressive filtration of smaller particulates than is generally carried out at the present time.


Asunto(s)
Puente Cardiopulmonar/instrumentación , Cateterismo Periférico/instrumentación , Filtros Microporos , Adulto , Procedimientos Quirúrgicos Cardíacos , Polvo , Embolia/patología , Diseño de Equipo , Femenino , Filtración/instrumentación , Cuerpos Extraños/patología , Gossypium , Humanos , Hipotermia Inducida , Masculino , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Minerales , Poliésteres , Porosidad , Propiedades de Superficie
14.
J Comput Assist Tomogr ; 23(3): 445-7, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10348453

RESUMEN

We present two cases of mechanical hemolysis due to malfunctioning prosthetic cardiac valves in which MRI was characteristic. The signal intensity of the renal cortex was much lower than that of the medulla on T2-weighted images due to deposition of hemosiderin in proximal convoluted tubules by intravascular hemolysis. These MR findings are identical to those in paroxysmal nocturnal hemoglobinuria.


Asunto(s)
Prótesis Valvulares Cardíacas , Hemoglobinuria Paroxística/diagnóstico , Hemólisis , Corteza Renal/patología , Falla de Prótesis , Femenino , Hemoglobinuria Paroxística/etiología , Hemosiderina , Humanos , Corteza Renal/diagnóstico por imagen , Imagen por Resonancia Magnética , Persona de Mediana Edad , Radiografía
15.
Bioorg Med Chem ; 8(1): 11-7, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10968259

RESUMEN

A set of 21 highly flexible competitive inhibitors of thymidylate synthase (TS; EC 2.1.1.45) covering a wide activity range (IC50 = 6 nM-100 microM) has been investigated by three-dimensional quantitative structure-activity relationship (3D-QSAR). CATALYST was used to generate three-dimensional hypotheses to study the common interaction features among a set of thymidylate synthase inhibitor. The verification of the hypothesis was achieved by using the molecules outside the training set.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Timidilato Sintasa/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Enlace de Hidrógeno , Modelos Moleculares , Relación Estructura-Actividad Cuantitativa
16.
Eur J Biochem ; 265(1): 430-40, 1999 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-10491201

RESUMEN

In order to define which structure of alpha-melanocyte-stimulating hormone (MSH) analogues plays a critical role for ligand-receptor interaction and selectivity, we analysed receptor-binding and cAMP-generating activity in Chinese hamster ovary cell lines stably transfected with rMC3R and hMC4R, as well as the NMR structures of chemically synthesized alpha-MSH analogues. Compared with [Ahx4]alpha-MSH, the linear MTII designated as alpha-MSH-ND revealed a preference for the MC4R, whereas its IC50 and EC50 values were comparable to those of MTII reported previously. Truncation of Ahx4 and Asp5 of alpha-MSH-ND remarkably decreased the receptor-binding and cAMP-generating activity. Meanwhile, maximum cAMP-generating activity was observed at a higher concentration (10(-5) M) of alpha-MSH-ND(6-10), and MC4R preference was changed into MC3R preference. In contrast, [Gln6]alpha-MSH-ND(6-10) lost its cAMP-generating activity almost completely, even though it bound to both receptors. Whereas the solution conformation of alpha-MSH-ND revealed a stable type I beta-turn structure, [Gln6]alpha-MSH-ND(6-10) revealed a tight gamma-turn composed of Gln6-D-Phe7-Arg8. Replacement of the His6 residue of alpha-MSH-ND by Gln, Asn, Arg or Lys decreased not only the receptor binding, but also the cAMP-generating activity in both the MC3R and the MC4R. The structure of [Gln6]alpha-MSH-ND exhibited a stable type I' beta-turn comprising Asp5, Gln6, D-Phe7 and Arg8. [Lys6]alpha-MSH-ND showed a greatly reduced binding affinity and cAMP-generating activity with the loss of MC4R selectivity. In NMR studies, [Lys6]alpha-MSH-ND also demonstrated a gamma-turn conformation around Lys6-DPhe7-Arg8. From the above results, we conclude that a type I beta-turn conformation comprising the residues Asp5-His6-(D-Phe7)-Arg8 was important for receptor binding and activation, as well as the selectivity of MSH analogues.


Asunto(s)
Proteínas Recombinantes/metabolismo , alfa-MSH/análogos & derivados , alfa-MSH/farmacología , Animales , Unión Competitiva , Células CHO , Cricetinae , AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Modelos Moleculares , Resonancia Magnética Nuclear Biomolecular , Unión Proteica , Estructura Secundaria de Proteína , Ratas , Receptor de Melanocortina Tipo 3 , Receptor de Melanocortina Tipo 4 , Receptores de Corticotropina/genética , Receptores de Corticotropina/metabolismo , Proteínas Recombinantes/genética , Transducción de Señal , Relación Estructura-Actividad
17.
Abdom Imaging ; 25(2): 124-8, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10675450

RESUMEN

BACKGROUND: To describe the radiologic findings of nonpolypoid gastric adenomas and to correlate them with pathologic findings. METHODS: During a 9-year period, we reviewed 49 pure gastric adenomas in 43 patients with positive radiologic findings. Of these adenomas, seven with atypical polypoid appearance were retrospectively included in the study. We reviewed these findings with double-contrast barium study and correlated them with the pathologic findings. RESULTS: Of seven nonpolypoid adenomas, four were depressed and three were flat at pathologic examination. All were diagnosed as early gastric carcinoma (five as type IIc, one as type IIb, one as type IIa + IIc) in upper gastrointestinal series. Three were located in the gastric angle, two in the lower body, and two in the antrum. Size ranged from 10 mm to approximately 25 mm (mean = 15 mm). Six lesions had nodular surface and five had convergency of the mucosal folds. A shallow depressed area was seen in six lesions. CONCLUSIONS: A considerable proportion of gastric adenomas presents as a depressed or flat lesion on double-contrast barium study because of histologic characteristics of decreased subjacent mucosa. Because the nonpolypoid adenoma has a greater potentional for malignancy, more precaution is needed during the follow-up of this uncommon lesion.


Asunto(s)
Adenoma/diagnóstico por imagen , Sulfato de Bario , Medios de Contraste , Neoplasias Gástricas/diagnóstico por imagen , Adenoma/patología , Pólipos Adenomatosos/patología , Anciano , Carcinoma/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Neoplasias Gástricas/patología
18.
Bioorg Med Chem ; 9(7): 1837-41, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11425585

RESUMEN

We have attempted to design a model dipeptide (acetyl dipeptide amide, Ac-CA1-CA2--NH(2)) that can adopt specifically typical torsion angles of the beta-I turn (phi(i+1), psi(i+1), phi(i+2), psi(i+2)=-60 degrees, -30 degrees, -90 degrees, 0 degrees ). The key of the design is the combination of constrained amino acids that prefer to adopt the desired torsion angles. We chose Aib (aminoisobutyric acid) as the first residue of which phi and psi angles must be -60 degrees and -30 degrees, respectively. Then, we selected an azaamino acid as the second residue since previous studies have indicated that they prefer to adopt +/-90 degrees of phi angle and 0 degrees or 180 degrees of psi angle. The conformational preference of the resulting Ac-Aib-AzGly--NH(2) is investigated using ab initio methods. The conformations implying beta-I and beta-I' turns are energetically most favorable, as we expected. Thus, we synthesized the designed molecule on the solid phase considering the future generation of combinatorial libraries using an automatic peptide synthesizer. Then, NMR spectroscopy was carried out to confirm their conformational preference in solution was carried out. The results indicated that the Ac-Aib-AzGly--NH(2) adopt beta-I or beta-I' turns in solution forming an intramolecular hydrogen bonding between Ac--C(O) and terminal NH(2). We believe that such a small peptidomimetic template is highly useful for the design of drug candidates and molecular devices.


Asunto(s)
Dipéptidos/química , Imitación Molecular , Dipéptidos/síntesis química , Resonancia Magnética Nuclear Biomolecular , Estructura Secundaria de Proteína
19.
Eur J Biochem ; 268(3): 582-91, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11168397

RESUMEN

Melanocortins are known to be involved in the regulation of feeding behavior. These hormones mediate their effects through G-protein-coupled receptors by stimulating adenylate cyclase. In this study we describe the functional response of melanocortin 4 receptor (MC4R) and melanocortin 3 receptor (MC3R) in HEK 293T cells, by using a luciferase reporter gene under the transcriptional control of a cAMP-responsive element (CRE) as a monitor of intracellular cAMP levels and cAMP-regulated gene expression. We were able to show that MC4R and MC3R expressed in the human cell line HEK 293T stimulate transcription induced by stimulation with different analogs of alpha-melanocyte-stimulating hormone (alpha-MSH) at different levels. In our assay of CRE-mediated gene transcription activity, alpha-MSH-ND was the most efficient alpha-MSH analog for MC4R whereas NDP-MSH was the most efficient for MC3R. Changing the His6 residue of alpha-MSH-ND to Gln or Lys markedly decreased CRE-mediated luciferase activity for MC3R compared with MC4R. On analysis by modeling the receptor-ligand complex by NMR, [Gln6]alpha-MSH-ND and [Lys6]alpha-MSH-ND showed different conformational interactions between MC3R and MC4R. Furthermore, the maximum coupling efficiency of MC4R and MC3R to G proteins was different; MC4R showed only 30-50% of the maximum activity induced by MC3R. In total, our results suggest that a differential receptor-ligand interaction is involved and that the relative interactions of MC3R and MC4R with G protein are possibly quantitatively and qualitatively different.


Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , AMP Cíclico/metabolismo , Regulación de la Expresión Génica , Receptores de Corticotropina/metabolismo , Transcripción Genética , Hormona Adrenocorticotrópica/análogos & derivados , Hormona Adrenocorticotrópica/química , Aminoácidos/química , Animales , Sitios de Unión , Northern Blotting , Células CHO , Línea Celular , Cricetinae , Genes Reporteros , Humanos , Ligandos , Luciferasas/metabolismo , Espectroscopía de Resonancia Magnética , Modelos Químicos , Modelos Moleculares , Mutación , Unión Proteica , Receptor de Melanocortina Tipo 3 , Receptor de Melanocortina Tipo 4 , Receptores de Corticotropina/química , Elementos de Respuesta , Factores de Tiempo , alfa-MSH/química , alfa-MSH/metabolismo
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