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2.
Oncogene ; 20(55): 7987-91, 2001 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-11753681

RESUMEN

Neoplastic progression in Barrett's esophagus is a multi-step process in which the metaplastic columnar epithelium sequentially evolves through a metaplasia-dysplasia-carcinoma sequence. The expression and DNA copy number of key cell cycle regulatory genes in paired normal and Barrett's esophagus samples was evaluated. Protein levels were evaluated in 60 formalin-fixed, paraffin-embedded human tissues by immunohistochemistry. DNA copy number from 20 fresh tissue pairs was analysed by Southern blot analysis. All normal mucosal samples expressed the p27(kip1) protein, but did not display appreciable nuclear staining for p16(kip4), p21(cip1) or cyclins D1 and E. Barrett's metaplastic specimens displayed increased expression levels of p16(kip4) (74%), p21(cip1) (89%) and cyclins D1 (43%) and E (37%). p27 protein was absent in three cases. There was a significant correlation between the expression of p16(kip4) and cyclin E, and p21(cip1) and p27(kip4) with cyclin D1. DNA analysis did not reveal any amplification or deletion of these genes. Acid suppression, however, was associated with significantly lower expression levels of key cell cycle proteins. Increased expression of key cell cycle regulatory genes appears to occur early in the neoplastic progression associated with Barrett's esophagus. Treatment with proton pump inhibitors appears to alter this increased expression.


Asunto(s)
Esófago de Barrett/genética , Esófago de Barrett/patología , Ciclo Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inhibidores de la Bomba de Protones , Adulto , Anciano , Anciano de 80 o más Años , Antiulcerosos/farmacología , Esófago de Barrett/tratamiento farmacológico , Ciclina D1/genética , Ciclina E/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/genética , ADN de Neoplasias/análisis , ADN de Neoplasias/genética , Inhibidores Enzimáticos/uso terapéutico , Femenino , Dosificación de Gen , Genes Supresores de Tumor , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Antígeno Nuclear de Célula en Proliferación/genética , Bombas de Protones/metabolismo
3.
J Biol Chem ; 274(48): 34164-73, 1999 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-10567388

RESUMEN

Serpins represent a diverse class of endogenous protease inhibitors that regulate important biological functions. In consideration of the importance of regulated proteolysis within secretory vesicles for the production of peptide hormones and neurotransmitters, this study revealed the molecular identity of a novel serpin, endopin 1, that is localized to neurosecretory vesicles of neuropeptide-containing chromaffin cells (chromaffin granules). Endopin 1 of 68-70 kDa was present within isolated chromaffin granules. Stimulated cosecretion of endopin 1 with chromaffin granule components, [Met]enkephalin and a cysteine protease known as "prohormone thiol protease," demonstrated localization of endopin 1 to functional secretory vesicles. Punctate, discrete immunofluorescence cellular localization of endopin 1 in chromaffin cells was consistent with its secretory vesicle localization. Endopin 1 contains a unique reactive site loop with Arg as the predicted P1 residue, suggesting inhibition of basic residue-cleaving proteases; indeed, trypsin was potently inhibited (K(i(app)) of 5 nM), and plasmin was moderately inhibited. Although endopin 1 possesses homology with alpha(1)-antichymotrypsin, chymotrypsin was not inhibited. Moreover, endopin 1 inhibited the chromaffin granule prohormone thiol protease (involved in proenkephalin processing). These results suggest a role for the novel serpin, endopin 1, in regulating basic residue-cleaving proteases within neurosecretory vesicles of chromaffin cells.


Asunto(s)
Células Cromafines/química , Sistemas Neurosecretores/química , Serpinas/genética , Médula Suprarrenal/química , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bovinos , Células Cromafines/metabolismo , Gránulos Cromafines/química , Gránulos Cromafines/metabolismo , Clonación Molecular , Cisteína Endopeptidasas/metabolismo , ADN Complementario/química , ADN Complementario/genética , Endopeptidasas/metabolismo , Encefalina Metionina/metabolismo , Encefalinas/metabolismo , Técnica del Anticuerpo Fluorescente , Expresión Génica , Glicoproteínas/análisis , Hidrólisis , Datos de Secuencia Molecular , Inhibidores de Proteasas , Precursores de Proteínas/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/fisiología , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Serpinas/análisis , Serpinas/fisiología , Tripsina/metabolismo
6.
Isr J Med Sci ; 30(12): 880-5, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8002268

RESUMEN

In the framework of an epidemiologic study we collected data on all the 162 patients with achalasia in central Israel. The mean (+/- SD) follow-up was 9.9 +/- 8.7 years (range 1-52). At the last, as compared to the initial examination, the clinical condition of the patients had improved: 38% were without dysphagia as compared to 0% initially, 67% did not vomit and 92% did not complain of aspiration as compared to 17% and 68% initially, and 67% did not complain of chest pain as against 36% initially. In contrast, X-ray examinations, endoscopy as well as manometry did not show major changes. Esophageal retention of a semisolid radiolabeled meal 10 min after ingestion was 46 +/- 25% initially and 34 +/- 26% at last examination (NS). Medical therapy was given to 99 patients and a beneficial response was initially noted in 65% of them. About 88.7% had a beneficial response to surgery and 82.7% to pneumatic dilatations which were associated with a 7.3% perforation rate. Overall the clinical course of this unselected, regional group of patients was better than expected.


Asunto(s)
Acalasia del Esófago/fisiopatología , Acalasia del Esófago/terapia , Adolescente , Adulto , Anciano , Niño , Preescolar , Trastornos de Deglución/diagnóstico , Dilatación , Acalasia del Esófago/diagnóstico , Esofagoscopía , Femenino , Estudios de Seguimiento , Humanos , Lactante , Israel , Masculino , Manometría , Persona de Mediana Edad , Nifedipino/uso terapéutico , Nitratos/uso terapéutico , Encuestas y Cuestionarios , Vómitos/diagnóstico
8.
J Intern Med ; 236(3): 341-3, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8077892

RESUMEN

DESIGN: A prospective randomized, double-blind, placebo-controlled, cross-over clinical trial. SETTING: A university hospital. SUBJECTS: Twenty-one patients with symptomatic recurrent aphthous stomatitis (RAS), unresponsive to conventional treatment were enrolled. They were divided into three groups. INTERVENTION: In a cross-over trial, the patients received an oral suspension of sucralfate, an antacid solution or a placebo for 2 years. RESULTS: After 2 years of follow-up, sucralfate was found to be superior to both placebo and antacid (P < 0.001) with regard to duration of pain, reduction of the healing period, response time to first treatment and duration of remission. CONCLUSION: Sucralfate suspension should be added to the armament of treatment modalities of RAS.


Asunto(s)
Estomatitis Aftosa/tratamiento farmacológico , Sucralfato/uso terapéutico , Administración Bucal , Adolescente , Adulto , Anciano , Antiácidos/uso terapéutico , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Sucralfato/administración & dosificación , Suspensiones , Resultado del Tratamiento
9.
J Med ; 25(5): 261-9, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7730733

RESUMEN

Bleeding from the upper gastrointestinal tract is one of the most common medical emergencies. Admission of patients to a specialized care unit may reduce morbidity and mortality. All patients admitted to the Tel Aviv Medical Center, between January 1, 1983 and December 31, 1990 with acute upper gastrointestinal bleeding, or those who bled while in the hospital, were seen and assessed by a senior member of the gastrointestinal service. Endoscopy was performed within 24 hr of admission. A total of 1110 endoscopies were performed. Duodenal ulcer was the main source of bleeding (40.0%). Injection of a vasoconstrictor was used for very small blood vessels. Thermal methods were used for small or medium sized vessels, or for oozing from a margin ulcer; both with equal rates of success. 153 (13.8%) surgical procedures were performed. Three (0.37) patients had endoscopic cardiovascular complications; one of them died. The in-hospital mortality was 5.9%. Increasing age, other medical problems, rebleeding and an admission hemoglobin of 8 g/dL or less, were associated with increased mortality. Our policy of early clinical and endoscopic assessment, and rapid surgical intervention in those at high risk, markedly improved survival.


Asunto(s)
Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Úlcera Duodenal/complicaciones , Endoscopía/métodos , Endoscopía/estadística & datos numéricos , Femenino , Hemorragia Gastrointestinal/etiología , Hemoglobinas , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Mortalidad , Pronóstico , Úlcera Gástrica/complicaciones , Factores de Tiempo
10.
Scand J Gastroenterol ; 28(11): 958-62, 1993 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8284630

RESUMEN

The transformation of xenobiotics and endogenous compounds to active carcinogens and their subsequent deactivation as an aid to eradication may be important in the etiology of some gastrointestinal cancers. In mammals the gastrointestinal tract has been shown to be an important site of inducible enzyme systems active in mucosal biotransformation, but few data are available in man. The mucosal activity of CYPIA1 (formerly aryl hydrocarbon hydroxylase), a potential carcinogen-activating enzyme, and catechol-O-methyl transferase, a potential carcinogen-inactivating enzyme were determined in colonic tissue obtained by biopsy. There were no significant differences in activity rates in normal mucosa between colorectal cancer and healthy persons, but significant differences are seen in patients with a history of neoplasia with no evidence of recurrence. The levels of activity of these carcinogen-inductive and -protective enzymes may be prognostic markers, in that the balance or imbalance could play a role in the recurrence of neoplasia. This will require confirmation and prospective studies.


Asunto(s)
Hidrocarburo de Aril Hidroxilasas/metabolismo , Biomarcadores de Tumor/metabolismo , Catecol O-Metiltransferasa/metabolismo , Colon/enzimología , Neoplasias Colorrectales/enzimología , Mucosa Intestinal/enzimología , Recto/enzimología , Adulto , Anciano , Biopsia , Colon/patología , Colonoscopía , Neoplasias Colorrectales/patología , Femenino , Humanos , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Recto/patología , Factores de Riesgo
12.
Hepatogastroenterology ; 40(2): 107-9, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8509038

RESUMEN

We have reviewed the eight years of experience with gastric polypoid lesions of a university hospital serving the Tel Aviv area, and analyzed 188 polyps. No clinical or endoscopic findings were able to distinguish the polyp variants prior to histological examination. The most frequent type of polyp was the hyperplastic polyp (45.2%), followed by the inflammatory type (29.3%). There were six cases of adenoma and ten cases of gastric carcinoma. The polyps were distributed equally within the body (44.7%) and antrum (48.9%), while the fundus was rarely involved (6.3%). Our findings are compatible with the statement that in general there is no distinction between the histological types classified by sex, age, location, symptoms or endoscopic appearance. Nevertheless, this is the first report of a higher incidence of gastric polyps among Ashkenazi Jews than non-Ashkenazi Jews with identical sex distribution.


Asunto(s)
Judíos , Pólipos/etnología , Neoplasias Gástricas/etnología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Incidencia , Israel/epidemiología , Masculino , Persona de Mediana Edad , Pólipos/patología , Estudios Retrospectivos , Estómago/patología , Neoplasias Gástricas/patología
13.
Liver ; 12(3): 107-11, 1992 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-1501515

RESUMEN

Nucleating factors are thought to be responsible for the more rapid nucleation of gallbladder bile from patients with gallstones as compared to controls. Biliary proteins and, in particular, mucus and non-mucus glycoproteins are the focus of current research. Non-protein nucleating factors were not extensively investigated. In this study we studied the role of free fatty acids (FFA) as possible nucleating factors. Palmitic, oleic and linoleic acid were added to model biles in increasing concentrations from 0 to 20 mu mol/ml. The nucleation time of model biles decreased to 45%-60% of the initial following the addition of 0.5 to 1 mu mol/ml of each of the three fatty acids. Only a small further decrease in the nucleation time was noted with higher concentrations of up to 20 mu mol/ml. The pronucleating effect of FFA added to whole model bile was also examined in the isolated vesicular and non-vesicular fractions. The decrease in the nucleation time at each concentration of the three fatty acids was in the following order of magnitude: whole bile greater than vesicular phase greater than non-vesicular phase. The addition of each of the three fatty acids resulted in a partial solubilization of vesicles, with transfer of their lipid contents to the non-vesicular fraction. The effect was more marked with oleic acid and least marked with linoleic acid. The vesicular cholesterol to phospholipid ratio did not change following the addition of exogenous free fatty acids. Studies with labeled FFA showed that they migrated with the non-vesicular fraction on gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Bilis/química , Colelitiasis/química , Colesterol/química , Ácidos Grasos no Esterificados/química , Humanos
15.
Harefuah ; 119(3-4): 110-1, 1990 Aug.
Artículo en Hebreo | MEDLINE | ID: mdl-2227665
16.
Harefuah ; 117(3-4): 103-4, 1989 Aug.
Artículo en Hebreo | MEDLINE | ID: mdl-2680824
17.
J Clin Gastroenterol ; 11(3): 331-4, 1989 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-2754222

RESUMEN

Acute obstruction of the left side of the colon is traditionally treated by colostomy, which entails two or three surgical procedures usually in a high-risk group of patients. We present a new nonsurgical approach by which decompression of the bowel is achieved with a tube introduced proximal to the obstruction with the aid of a flexible sigmoidoscope. This procedure was successful in six of nine patients with left-sided large-bowel obstruction, thus avoiding staged surgery and allowing one definitive operation. No complications were encountered.


Asunto(s)
Enfermedades del Colon/terapia , Obstrucción Intestinal/terapia , Intubación , Sigmoidoscopía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad
19.
Endoscopy ; 20(6): 292-3, 1988 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-3229388

RESUMEN

The clinical significance of unexplained dilation of the common bile duct (CBD) seen at endoscopic retrograde cholangiopancreatography (ERCP) in non-jaundiced patients with abdominal pain, was studied in a group of 14 patients. A CBD diameter of more than 15 mm was associated with choledocholithiasis (29%), periampullary carcinoma (14%), papillary stenosis (14%), or no definite pathology (43%) during a follow-up of 20 months. Dilation of the CBD exceeding 20 mm, was associated with periampullary carcinoma or papillary stenosis in 80% of the patients. It is recommended that such a group of patients be followed very closely, and the ERCP examination repeated within a few months.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Enfermedades del Conducto Colédoco/diagnóstico , Anciano , Enfermedades del Conducto Colédoco/patología , Dilatación Patológica , Femenino , Humanos , Masculino , Persona de Mediana Edad
20.
J Hosp Infect ; 12(1): 7-12, 1988 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-2905378

RESUMEN

At the Tel-Aviv Medical Center, five of 720 (0.69%) patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) subsequently developed septicaemia. One of these patients (0.14%) died as a direct result and three other septicaemic patients died from other complications. The most important risk factor associated with infectious complications was obstructive jaundice. Retrospective analysis of our data revealed that no cases of septicaemia developed in patients given prophylactic antibiotics, whereas 4.3% of patients who received no prophylactics developed infectious complications. Prophylactic antibiotics are therefore recommended for patients undergoing ERCP who have biliary obstruction.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Infección Hospitalaria/etiología , Sepsis/etiología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Femenino , Humanos , Israel , Masculino , Persona de Mediana Edad , Premedicación , Estudios Retrospectivos , Factores de Riesgo , Sepsis/epidemiología , Sepsis/prevención & control
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