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1.
Psychol Med ; 42(7): 1535-45, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22085725

RESUMEN

BACKGROUND: Although many studies indicate that maternal smoking during pregnancy (SDP) is correlated with later offspring antisocial behavior (ASB), recent quasi-experimental studies suggest that background familial factors confound the association. The present study sought to test alternative etiological hypotheses using multiple indices of adolescent ASB, comparing differentially exposed siblings, and testing assumptions in the sibling-comparison design. METHOD: The study examined the association between maternal SDP and adolescent-reported ASB, criminal convictions and membership in a group of individuals with early-starting and chronic ASB among 6066 offspring of women from the National Longitudinal Survey of Youth, a representative sample of women in the USA. The analyses controlled for statistical covariates and examined associations while comparing differentially exposed siblings. RESULTS: At the population level, each additional pack of cigarettes per day predicted greater mean adolescent-reported ASB symptoms [ratio of means 1.15, 95% confidence interval (CI) 1.08-1.22], odds of being in the top 10% of ASB [odds ratio (OR) 1.34, 95% CI 1.10-1.65], hazard of a criminal conviction [hazard ratio (HR) 1.51, 95% CI 1.34-1.68] and odds of chronic ASB (OR 1.57, 95% CI 1.25-1.99). SDP robustly predicted most assessments of ASB while controlling for measured covariates. When siblings exposed to differing levels of SDP were compared, however, all of the associations were attenuated and were not statistically significant: adolescent-reported mean ASB (ratio of means 0.86, 95% CI 0.74-1.01), high ASB (OR 0.67, 95% CI 0.41-1.12), criminal conviction (HR 0.98, 95% CI 0.66-1.44) and chronic ASB (OR 0.80, 95% CI 0.46-1.38). CONCLUSIONS: The results strongly suggest that familial factors account for the correlation between SDP and offspring adolescent ASB, rather than a putative causal environmental influence of SDP.


Asunto(s)
Conducta del Adolescente , Trastorno de Personalidad Antisocial/epidemiología , Modelos Estadísticos , Complicaciones del Embarazo/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Fumar/epidemiología , Adolescente , Adulto , Causalidad , Niño , Crimen/estadística & datos numéricos , Femenino , Humanos , Estudios Longitudinales , Masculino , Embarazo , Factores de Riesgo , Hermanos , Medio Social , Estados Unidos/epidemiología , Adulto Joven
2.
Arch Surg ; 136(9): 990-4, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11529819

RESUMEN

HYPOTHESIS: Stereotactic core biopsy (SCB) is more cost-effective than needle-localized biopsy (NLB) for evaluation and treatment of mammographic lesions. DESIGN: A computer-generated mathematical model was developed based on clinical outcome modeling to estimate costs accrued during evaluation and treatment of suspicious mammographic lesions. Total costs were determined for evaluation and subsequent treatment of cancer when either SCB or NLB was used as the initial biopsy method. Cost was estimated by the cumulative work relative value units accrued. The risk of malignancy based on the Breast Imaging Reporting Data System (BIRADS) score and mammographic suspicion of ductal carcinoma in situ were varied to simulate common clinical scenarios. MAIN OUTCOME MEASURES: Total cost accumulated during evaluation and subsequent surgical therapy (if required). RESULTS: Evaluation of BIRADS 5 lesions (highly suggestive, risk of malignancy = 90%) resulted in equivalent relative value units for both techniques (SCB, 15.54; NLB, 15.47). Evaluation of lesions highly suspicious for ductal carcinoma in situ yielded similar total treatment relative value units (SCB, 11.49; NLB, 10.17). Only for evaluation of BIRADS 4 lesions (suspicious abnormality, risk of malignancy = 34%) was SCB more cost-effective than NLB (SCB, 7.65 vs. NLB, 15.66). CONCLUSIONS: No difference in cost-benefit was found when lesions highly suggestive of malignancy (BIRADS 5) or those suspicious for ductal carcinoma in situ were evaluated initially with SCB vs. NLB, thereby disproving the hypothesis. Only for intermediate-risk lesions (BIRADS 4) did initial evaluation with SCB yield a greater cost savings than with NLB.


Asunto(s)
Biopsia/economía , Neoplasias de la Mama/economía , Mamografía , Biopsia/métodos , Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/diagnóstico , Carcinoma Intraductal no Infiltrante/economía , Carcinoma Intraductal no Infiltrante/terapia , Ahorro de Costo , Análisis Costo-Beneficio , Femenino , Humanos , Escisión del Ganglio Linfático/economía , Mastectomía/economía , Mastectomía Segmentaria/economía , Modelos Teóricos , Escalas de Valor Relativo , Técnicas Estereotáxicas
3.
Am J Vet Res ; 62(9): 1467-77, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11560279

RESUMEN

OBJECTIVES: To determine concentrations of matrix metalloproteinase (MMP)-2 and -9 in synovial fluid; and mRNA expression of MMP-1, -13, and -3; interleukin[IL]-1alpha and beta; and tumor necrosis factor (TNF)-alpha in synovial membrane and articular cartilage from horses with naturally occurring joint disease. SAMPLE POPULATION: Synovial fluid (n = 76), synovial membrane (59), and articular cartilage (45) from 5 clinically normal horses and 55 horses with joint disease categorized as traumatic (acute [AT] or chronic [CT]), osteochondritis dissecans (OCD), or septic (S). PROCEDURE: Synovial fluid gelatinase concentrations were analyzed, using zymography. Synovial membrane and articular cartilage mRNA expression for MMP-1, -3, and -13, IL-1alpha and beta, TNF-alpha, type-II collagen, and aggrecan were analyzed, using quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Synovial fluid pro-MMP-2 concentration was significantly higher in diseased joints than normal joints. Septic joints had significantly higher concentrations of pro and active MMP-9. Stromelysin-1 was expressed in > or = 80% of synovial membrane and articular cartilage samples and was strongly influenced by age. Collagenases were rarely expressed, with MMP-13 expressed only in diseased joints. Interleukin-1beta expression was significantly higher in all OCD samples and was influenced by age. Tumor necrosis factor-alpha expression was significantly higher in cartilage from joints with AT and OCD. There was no correlation between MMP or cytokines and type-II collagen or aggrecan expression. CONCLUSIONS AND CLINICAL RELEVANCE: Matrix metalloproteinase-2 and -3 are abundant in naturally occurring joint disease and normal joints. Interleukin-1beta and TNF-alpha may be important in the pathogenesis of OCD. Age affects MMP and IL-1beta concentrations.


Asunto(s)
Enfermedades de los Caballos/enzimología , Artropatías/veterinaria , Metaloproteinasas de la Matriz/biosíntesis , Líquido Sinovial/enzimología , Animales , Western Blotting/veterinaria , Cartílago Articular/enzimología , Electroforesis en Gel de Poliacrilamida/veterinaria , Regulación Enzimológica de la Expresión Génica , Caballos , Interleucina-1/análisis , Interleucina-1/biosíntesis , Artropatías/enzimología , Metaloproteinasas de la Matriz/análisis , ARN Mensajero/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/biosíntesis
4.
Ann Thorac Surg ; 72(2): 593-6, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11515902

RESUMEN

Ivor Lewis esophagectomy consists of a laparotomy and right thoracotomy for resection of the intrathoracic esophagus. Recent advances in minimally invasive surgical technology have allowed surgeons to apply laparoscopy and thoracoscopy to perform esophagectomy. However, there have been few reports that describe a totally minimally invasive Ivor Lewis esophagectomy. We present a case of combined laparoscopic and thoracoscopic resection of the distal third esophagus with an intrathoracic esophagogastric reconstruction for esophageal carcinoma.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/instrumentación , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Adulto , Unión Esofagogástrica/cirugía , Humanos , Laparoscopía , Masculino , Instrumentos Quirúrgicos , Toracoscopía
5.
Arch Surg ; 136(6): 649-55, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11387001

RESUMEN

HYPOTHESIS: The responsibility for childbearing and child care has a major effect on general surgical residency and subsequent surgical practice. METHODS: A survey of all graduates from a university general surgical training program between 1989 and 2000. RESULTS: Twenty-seven women and 44 men completed general surgical training at our university during the period, and 42 (59%) responded to our survey. The age at completion of the residency was 34.0 +/- 2.2 years for men and 33.9 +/- 2.8 years for women. During residency, 64% (14/22) of the men and 15% (3/20) of the women had children. At the time of the survey, 21 (95%) of the men and 8 (40%) of the women had children. Most residents (24 [57%] of 42) relied on their spouse for child care. During surgical practice, 18 (43%) indicated that they rely on their spouse; 19 (45%) use day care, home care, or both; and (8%) of 26 are unsatisfied with their current child care arrangement. During training, 38% (5/13) of men and 67% (2/3) of women took time off for maternity leave, paternity leave, or child care. Two of 3 surgeons would like to have had more time off during residency; most men (70%, or 7 of 10) recommended a leave of 1 to 3 months, and all women preferred a 3-month maternity or child care leave of absence. During surgical practice, only 12% (2/17) of men but 64% (7/11) of women have taken time off for either childbearing or child care. Half of the respondents (21/42) have a formal leave of absence policy at work, 52% (11/21) of which are paid leave programs. Although the workweek of our practicing graduates is 69 +/- 16 hours for men and 64 +/- 12 hours for women, 62% (26/42) spend more than 20 hours per week parenting. More than 80% (27/32) would consider a part-time surgical practice for more parenting involvement; one third of the responders suggested that 30 hours a week constitutes a reasonable part-time practice, one third preferred fewer than 30 hours, and one third favored more than 30 hours per week. Data are presented as mean +/- SD. CONCLUSIONS: Childbearing and child care may have an enormous impact on one's decision to pursue a career in surgery. To attract and retain the best candidates for future surgeons, formal policies on the availability of child care services in the residency program and the workplace should be studied and implemented. Furthermore, national studies are needed to define appropriate, acceptable workweeks for part-time or flexible practices and the duration of leaves of absence for childbearing or child care.


Asunto(s)
Selección de Profesión , Cuidado del Niño/psicología , Cuidado del Niño/estadística & datos numéricos , Cirugía General , Internado y Residencia/estadística & datos numéricos , Trabajo de Parto , Cuerpo Médico de Hospitales/psicología , Cuerpo Médico de Hospitales/estadística & datos numéricos , Padres/psicología , Carga de Trabajo , Adulto , Actitud del Personal de Salud , Niño , Femenino , Identidad de Género , Cirugía General/educación , Humanos , Lactante , Masculino , Cuerpo Médico de Hospitales/educación , Cuerpo Médico de Hospitales/provisión & distribución , Permiso Parental/estadística & datos numéricos , Selección de Personal , Admisión y Programación de Personal/organización & administración , Embarazo , Salarios y Beneficios , Encuestas y Cuestionarios , Factores de Tiempo , Recursos Humanos
7.
Arch Surg ; 136(1): 60-4, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11146779

RESUMEN

HYPOTHESIS: Surgical residents and staff oncologists (surgical, medical, and radiation therapy) have similar opinions on participation in physician-assisted death for patients with terminal cancer. DESIGN: Prospective survey. SETTING: Tertiary care referral center. PARTICIPANTS: Residents undergoing surgical training (n = 56) and faculty oncologists (n = 24) of all specialties (surgical, medical, and radiation therapy). MAIN OUTCOME MEASURES: Subjects were queried regarding previous experience and willingness to participate (either directly or indirectly) in assisted death for terminal cancer patients. RESULTS: Response rates were 39% (22 of 56) for the residents and 87% (21 of 24) for the oncologists. Of those who responded, 86% (19 of 22) of the residents would aid any of the hypothetical patients with assisted death, whereas only 19% (4 of 21) of the staff oncologists expressed willingness to perform the same service. Furthermore, 32% (7 of 22) of the residents reported previous involvement in a case of assisted death from any disease, whereas only 19% (4 of 21) of the staff oncologists reported previous direct experience with assisted death in the terminal cancer patient. CONCLUSIONS: Surgical residents tend to have more experience with assisted death and are much more willing than staff oncologists to aid terminal cancer patients with this procedure. These opinions and practices are probably not the result of medical education but are developed from personal values.


Asunto(s)
Actitud del Personal de Salud , Internado y Residencia , Neoplasias , Suicidio Asistido , Adulto , Recolección de Datos , Femenino , Cirugía General/educación , Humanos , Masculino , Oncología Médica , Cuerpo Médico de Hospitales , Estudios Prospectivos , Encuestas y Cuestionarios
8.
Am J Surg ; 182(6): 702-6, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11839342

RESUMEN

BACKGROUND: Conventional imaging studies (computed tomography and endoscopic esophageal ultrasonography) used for preoperative evaluation of patients with esophageal cancer can be inaccurate for detection of small metastatic deposits. We evaluated the efficacy of minimally invasive surgical (MIS) staging as an additional modality for evaluation of patients with esophageal cancer. METHODS: Between December 1998 and February 2001, 33 patients with esophageal cancer were evaluated for surgical resection. Conventional imaging studies demonstrated operable disease in 31 patients and equivocal findings in 2 patients. All patients then underwent MIS staging (laparoscopy, bronchoscopy, and ultrasonography of the liver). We compared the results from surgical resection and MIS staging with those from conventional imaging. RESULTS: MIS staging altered the treatment plan in 12 (36%) of 33 patients; MIS staging upstaged 10 patients with operable disease and downstaged 2 patients with equivocal findings. MIS staging accurately determined resectability in 97% of patients compared with 61% of patients staged by conventional imaging. The specificity and negative predictive value for detection of unsuspected metastatic disease in MIS staging were 100% and 96%, respectively, compared with 91% and 65%, respectively, for conventional imaging studies. CONCLUSION: In addition to conventional imaging studies, MIS staging should be included routinely in the preoperative work-up of patients with esophageal cancer.


Asunto(s)
Neoplasias Esofágicas/patología , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estadificación de Neoplasias/métodos , Adulto , Anciano , Anciano de 80 o más Años , Broncoscopía , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Laparoscopía , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Ultrasonografía
9.
Arch Surg ; 135(8): 920-5, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10922253

RESUMEN

HYPOTHESIS: Minimally invasive esophagectomy can be performed as safely as conventional esophagectomy and has distinct perioperative outcome advantages. DESIGN: A retrospective comparison of 3 methods of esophagectomy: minimally invasive, transthoracic, and blunt transhiatal. SETTING: University medical center. PATIENTS: Eighteen consecutive patients underwent combined thoracoscopic and laparoscopic esophagectomy from October 9, 1998, through January 19, 2000. These patients were compared with 16 patients who underwent transthoracic esophagectomy and 20 patients who underwent blunt transhiatal esophagectomy from June 1, 1993, through August 5, 1998. MAIN OUTCOME MEASURES: Operative time, amount of blood loss, number of operative transfusions, length of intensive care and hospital stays, complications, and mortality. RESULTS: Patients who had minimally invasive esophagectomy had shorter operative times, less blood loss, fewer transfusions, and shortened intensive care unit and hospital courses than patients who underwent transthoracic or blunt transhiatal esophagectomy. There was no significant difference in the incidence of anastomotic leak or respiratory complications among the 3 groups. CONCLUSION: Minimally invasive esophagectomy is safe and provides clinical advantages compared with transthoracic and blunt transhiatal esophagectomy.


Asunto(s)
Esofagectomía/métodos , Anciano , Análisis de Varianza , Anastomosis Quirúrgica/efectos adversos , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , Distribución de Chi-Cuadrado , Cuidados Críticos , Esofagectomía/efectos adversos , Femenino , Hospitalización , Humanos , Incidencia , Laparoscopía/efectos adversos , Laparoscopía/métodos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Complicaciones Posoperatorias , Insuficiencia Respiratoria/etiología , Estudios Retrospectivos , Seguridad , Tasa de Supervivencia , Toracotomía/efectos adversos , Toracotomía/métodos , Factores de Tiempo
11.
Arch Biochem Biophys ; 372(1): 69-79, 1999 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-10562418

RESUMEN

Insulin regulates a diverse array of signaling pathways involved in the control of growth, differentiation, proliferation, and metabolism. Insulin increases in glucose uptake via a protein kinase C-dependent pathway in target tissues such as fat and muscle are well documented. Insulin-regulated events, however, occur in all cells. The utilization of glucose as a preferred energy source is a ubiquitous event in eukaryotic cells. In NIH-3T3 fibroblasts, insulin treatment increased levels of the cPKC and nPKC activator, diacylglycerol. Insulin-responsive 2-[(3)H]deoxyglucose uptake was stimulated in a dose-dependent manner. The overexpression of protein kinase C (PKC)betaI, -betaII, -delta, -epsilon, and -zeta was used to investigate the specificity of PKC isozymes for insulin-sensitive glucose uptake. The stable overexpression of PKCbetaII, -delta, and -epsilon resulted in increases in insulin-stimulated 2-[(3)H]deoxyglucose uptake compared to vector control cells, while basal 2-deoxyglucose uptake levels were not elevated. Overexpression of PKCbetaI and PKCzeta isozymes had no further effect on basal or insulin-stimulated 2-deoxyglucose uptake. The PKC-specific inhibitor, CGP41251, blocked insulin effects on 2-deoxyglucose uptake but not its effects on tyrosine phosphorylation of cellular substrates. Insulin-stimulated 3-O-methylglucose uptake was also greater in cells overexpressing PKCbetaII, -delta, and -epsilon, compared to control cells. The increased responsiveness was not accompanied by conversion of 3T3 cells to the adipocyte phenotype or the increased expression of insulin receptors or glucose transporters (GLUT1-type). Insulin-stimulated recruitment of GLUT1 to plasma membranes of cells overexpressing PKCbetaII, -delta, and -epsilon, was greater than that in control cells. The data suggest that more than one PKC isozyme is involved in insulin signaling pathways in fibroblasts, resulting in increased GLUT1 transporter recruitment to cell membranes.


Asunto(s)
Glucosa/metabolismo , Insulina/farmacología , Isoenzimas/metabolismo , Proteína Quinasa C/metabolismo , 3-O-Metilglucosa/metabolismo , Células 3T3 , Animales , Transporte Biológico Activo/efectos de los fármacos , Desoxiglucosa/metabolismo , Diglicéridos/metabolismo , Inhibidores Enzimáticos/farmacología , Expresión Génica , Transportador de Glucosa de Tipo 1 , Isoenzimas/antagonistas & inhibidores , Isoenzimas/genética , Ratones , Proteínas de Transporte de Monosacáridos/metabolismo , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/genética , Receptor de Insulina/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transducción de Señal , Estaurosporina/análogos & derivados , Estaurosporina/farmacología
12.
Arch Surg ; 134(8): 869-74; discussion 874-5, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10443811

RESUMEN

HYPOTHESIS: We hypothesized that late pulmonary dead space fraction (Fd(late)) would be a useful tool to screen for pulmonary embolism (PE) in a group of surgical patients, including patients who required mechanical ventilation and patients with adult respiratory distress syndrome. DESIGN: We prospectively calculated Fd(late) in patients with suspected PE who underwent pulmonary angiography. SETTING: University-based, level I trauma center. MAIN OUTCOME MEASURE: Ability of Fd(late) to identify patients with PE. RESULTS: Twelve patients had 14 angiograms for suspected PE. The Fd(late) was 0.12 or above in all 5 patients who had PE; 4 required mechanical ventilation. The Fd(late) values were below 0.12 in 8 of 9 patients without PE. Four patients had adult respiratory distress syndrome. The Fd(late) had 100% sensitivity and 89% specificity for the detection of PE. CONCLUSIONS: The Fd(late) is a valuable tool for bedside screening of PE in surgical patients. We were able to accurately detect all PEs.


Asunto(s)
Enfermedad Crítica , Embolia Pulmonar/diagnóstico , Adulto , Pruebas Respiratorias , Dióxido de Carbono/análisis , Femenino , Humanos , Masculino , Sistemas de Atención de Punto , Arteria Pulmonar/diagnóstico por imagen , Embolia Pulmonar/complicaciones , Radiografía , Respiración Artificial , Espacio Muerto Respiratorio , Síndrome de Dificultad Respiratoria/complicaciones , Pruebas de Función Respiratoria , Sensibilidad y Especificidad
13.
Oncogene ; 16(1): 53-60, 1998 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-9467942

RESUMEN

Protein kinase C-epsilon (PKC-epsilon) has been shown to increase growth and cause malignant transformation when overexpressed in NIH3T3 cells, whereas PKC-delta reduced fibroblast growth. Two reciprocal chimeric proteins (PKC-epsilondelta and PKC-deltaepsilon were constructed by exchanging the regulatory and catalytic domains of PKC-delta and -epsilon and were stably overexpressed in NIH3T3 cells. Fibroblasts that overexpressed either chimera showed maximum cell density and morphology that were intermediate between cells overexpressing PKC-delta and those that overexpressed PKC-epsilon. Moreover, all lines that expressed chimeras were capable of anchorage-independent growth in the presence of TPA, which indicated that both the regulatory and catalytic domains of PKC-epsilon could independently induce NIH3T3 transformation, although the combination of both domains, as found in PKC-epsilon, was the most active form. In contrast, the translocation pattern and ability to induce tumors in nude mice was attributable to the catalytic domains exclusively. In particular, cells that expressed PKC-deltaepsilon retained PKC-epsilon's full potency of tumorgenicity when injected into nude mice. In sum, our findings not only reinforce the concept that only certain PKC isozymes contribute to carcinogenesis but also show that different domains of PKCs mediate the physiologically distinguishable events of transformation and tumorgenesis.


Asunto(s)
Isoenzimas/metabolismo , Proteína Quinasa C/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Células 3T3 , Animales , Catálisis , División Celular , Transformación Celular Neoplásica , Isoenzimas/genética , Ratones , Ratones Desnudos , Proteína Quinasa C/genética , Proteína Quinasa C-delta , Proteína Quinasa C-epsilon , Proteínas Recombinantes de Fusión/genética , Acetato de Tetradecanoilforbol/farmacología
15.
J Biol Chem ; 272(1): 76-82, 1997 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-8995230

RESUMEN

The overexpression of protein kinase C-delta (PKC-delta), but not PKC-epsilon, enables the mouse myeloid cell line 32D to differentiate into macrophages when treated with phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). To determine the domain of PKC-delta that is responsible for this isotype-specific function, cDNAs that encode reciprocal chimeras of PKC-delta and -epsilon (PKC-delta epsilon and PKC-epsilon delta) were constructed by exchanging regulatory and kinase domains using polymerase chain reaction technology. Both chimeras were stably expressed in 32D cells using the pLTR expression vector and displayed protein kinase activity upon TPA treatment. TPA treatment of L epsilon delta, cells that overexpressed the PKC-epsilon delta chimera, induced a dramatically increased cell volume, surface adherence, surface expression of Mac-1 and Mac-3, lysozyme production, and phagocytosis. These are the characteristics of the macrophage phenotype found in TPA-treated 32D cells that overexpressed PKC-delta. In contrast, little effect was seen in L delta epsilon, 32D cells that overexpressed PKC-delta epsilon, with or without TPA treatment. A PKC inhibitor directed toward the catalytic domain of PKC, GF109203X, and a selective inhibitor of PKC-delta, Rottlerin, blocked the TPA-induced differentiation of PKC-epsilon delta-overexpressing 32D cells. These results demonstrate that the catalytic domain of PKC-delta contains the primary determinants for its activity in phorbol ester-induced macrophage differentiation.


Asunto(s)
Isoenzimas/química , Macrófagos/citología , Proteína Quinasa C/química , Animales , Antígenos de Diferenciación/metabolismo , Adhesión Celular , Diferenciación Celular/efectos de los fármacos , Línea Celular , Hematopoyesis/efectos de los fármacos , Activación de Macrófagos , Antígeno de Macrófago-1/metabolismo , Ratones , Fagocitosis , Forbol 12,13-Dibutirato/metabolismo , Proteína Quinasa C-delta , Proteína Quinasa C-epsilon , Proteínas Recombinantes de Fusión , Acetato de Tetradecanoilforbol/farmacología
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