Modificación del comportamiento celular bajo el efecto de estatinas en células de pared arterial (II). Alteraciones estructurales del citoesqueleto / Alterations in cell behaviour under the effect of statins in arterial wall cells (II). Changes in cytoskeletal structure

Algunos de los efectos clínicos de los inhibidores de la HMG-CoA-reductasa (estatinas) pueden no ser estrictamente dependientes del descenso de colesterol y del cLDL. Estos efectos, ajenos al propiamente hipocolesterolemiante, se conocen como efectos pleiotrópicos. En trabajos previos se ha demostrado que los efectos pleiotrópicos pueden tener como sustrato cambios en el comportamiento celular, valorando la movilidad y la adherencia celular. Ello, unido a los cambios en la tasa de proliferación celular así como la de apoptosis, obliga a pensar que algunos cambios estructurales pueden estar detrás de los efectos no estrictamente lipídicos. En el presente trabajo se ha intentado valorar los cambios inducidos en el citoesqueleto cuando se incuban células de pared vascular con estatinas. Se han empleado fibroblastos y fibras musculares lisas, y simvastatina y cerivastatina. Nuestros resultados han permitido confirmar que las estatinas inducen modificaciones en las estructuras actínicas de la célula mediante el empleo de tinciones con inmunofluorescencia y empleando anticuerpos anti-actina. Estos cambios podrían explicar las modificaciones celulares que se acompañan de variaciones en el comportamiento celular (AU)

Some of the clinical effects of HMG-CoA-reductase inhibitors (statins) may not bestrictly dependent on the decrease in cholesterols and LDL-cholesterol. These effects, whichare not related to their lipid lowering properties, are known as pleiotropic effects. In previous studies it has been shown that the pleiotropic effects may have changes in cellbehaviour, assessing cell mobility and adhesion as substrate. That, along with the changes in the cell proliferation rate as well as apoptosis, leads to thinking that structural changes maybe behind these not strictly lipid effects. In the present study, an attempt has been made to evaluate the changes induced in the cytoskeleton when vascular wall cells are incubated with statins. Fibroblast and smooth musclefibres, and simvastatin and cerivastatin have been used. Our results have been able to confirm that the statins induce changes in the act in structures of the cell by using stains with immunofluorescence as well as anti-actin antibodies (AU)

Classical markers like ER and ki-67, but also survivin and pERK, could be involved in the pathological response to gemcitabine, adriamycin and paclitaxel (GAT) in locally advanced breast cancer patients: results from the GEICAM/2002-01 phase II study

INTRODUCTION: The identification and validation of biomarkers of chemotherapy sensitivity is critical in order to individualise therapy in breast cancer. We evaluated pathological complete response (pCR) to GAT, and its correlation with tumour biomarkers before and after neoadjuvant chemotherapy. MATERIALS AND METHODS: Stage III (and stage II with T≥5 cm) breast cancer patients were included. Treatment consisted of adriamycin (40 mg/m(2)) day 1, and paclitaxel (150 mg/ m(2)) followed by gemcitabine (2000 mg/m(2)) day 2, every 14 days for six cycles. Tissue from pre-treatment biopsy and surgery was evaluated for biologic markers by immunohistochemistry. Two XPD single nucleotide polymorphisms (SNP) were also analysed. RESULTS: Forty-six patients entered the trial. Median age was 49.5 years (range 31-72); 25 patients (54%) were pre-menopausal; 12 (26%) were ER-PgR-negative; pCR was observed in 17% (95% CI: 6.4-28.4) of patients. Significant differences in marker expression (mean±SD) in correlation to pathological response were only found in Ki- 67. After treatment, tumours showed lower Ki-67-, surviving- and pERK-positive cells. No correlation between XPD polymorphisms and pCR was found. The overall response rate was 89% (95% CI: 80.1-98.1). Fifteen patients (33%) underwent breast-conserving surgery. The most frequent grade 3 or 4 toxicities were neutropenia (with one febrile neutropenia) and asthenia. CONCLUSION: These results show an effective regimen with acceptable tolerability. Our data suggest that not only classical markers (ER, Ki-67), but also survivin and pERK could be involved in the response to GAT, which may contribute to therapy individualisation in future study designs (AU)

Peripheral Arterial Disease study (PERART): prevalence and predictive values of asymptomatic peripheral arterial occlusive disease related to cardiovascular morbidity and mortality / Peripheral Arterial Disease study (PERART): prevalence and predictive values of asymptomatic peripheral arterial occlusive disease related to cardiovascular morbidity and mortality

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[Satellite manifestations of internal diseases]. / Manifestaciones satélites de las enfermedades internas.

AIMS: Define the concept of satellite manifestations (SM) and to determine the number and types of them that appear in the diseases of each one of the subspecialties of the Internal Medicine. METHODS: 290 diseases are reviewed in agreements of Internal Medicine and specialties books and in each one are described the types of SM that they present. RESULTS: The respiratory diseases are the group that more SM presents and the less one the neurological. The most frequent type of SM are dermatological. The diseases that have more variety of types of SM are the endocrinologicals. Analyzing the percentages of every type of SM in relation with the number of diseases of every group, the highest are the dermatological SM in cardiac diseases. CONCLUSIONS: The SM are a very frequent phenomenon in the current medical practice and express the holistic character of the disease. His knowledge is indispensable in the internal medicine and subspecialties, where they can suppose a help in the diagnoses, though a bad knowledge of his reality can mean the opposite.

Manifestaciones satélites de las enfermedades internas / Satellite manifestations of internal diseases

Objetivos. Definir el concepto de manifestaciones satélites (MS) y determinar que número y tipos de ellas aparecen en las enfermedades de cada una de las subespecialidades de la Medicina Interna. Método: Se revisan 290 enfermedades en tratados de Medicina Interna y de especialidades y en cada una de ellas se describen los tipos de MS que presentan. Resultados: Las enfermedades respiratorias son las que mas MS presentan y las que menos las neurológicas. El tipo mas frecuente de MS es dermatológico. Las enfermedades que más variedad tienen de tipos de MS son las endocrinas. Analizando los porcentajes de cada tipo de MS en relación con el número de enfermedades de cada grupo, los mas altos son de MS dermatológicas en enfermedades cardiacas. Conclusiones: Las MS son un fenómeno muy frecuente en la clínica médica actual y expresan el carácter holístico de la enfermedad. Su conocimiento es imprescindible en la clínica internista y subespecializada, donde pueden suponer una ayuda diagnostica, aunque un mal conocimiento de su realidad pueden significar lo contrario

Aims: Define the concept of satellite manifestations (SM) and to determine the number and types of them that appear in the diseases of each one of the subspecialities of the Internal Medicine. Methods: 290 diseases are reviewed in agreements of Internal Medicine and specialities books and in each one are described the types of SM that they present. Results: The respiratory diseases are the group that more SM presents and the less one the neurological. The most frequent type of SM are dermatological. The diseases that have more variety of types of SM are the endocrinologicals. Analyzing the percentages of every type of SM in relation with the number of diseases of every group, the highest are the dermatological SM in cardiac diseases. Conclusions: The SM are a very frequent phenomenon in the current medical practice and express the holistic character of the disease. His knowledge is indispensable in the internal medicine and subspecialities, where they can suppose a help in the diagnoses, though a bad knowledge of his reality can mean the opposite

[Subcutaneous panniculitis at a third level hospital retrospective study of 113 cases]. / Paniculitis subcutáneas en un hospital de tercer nivel: estudio retrospectivo de 113 casos.

INTRODUCTION: The panniculitides or hypodermitis are a wide and heterogeneous group of diseases characterized by the presence of subcutaneous inflammatory nodules located generally in low limbs. OBJECTIVES: Show the clinicopathologic characteristics of the cases diagnosed as panniculitis for a 5 years period; their epidemiology, etiopathogenic factors, evolution and treatment. MATERIAL AND METHODS: A retrospective study of 113 patients diagnosed as panniculitis by histopathologic report of cutaneous biopsy since 1997 to 2001 were performed. RESULTS: The sex proportion was of 4.65 women to every man. The mean age of these patients was 49 +/- 20 years old. 100% had legs affectation, 7.1% in arms, 5.9% in trunk and 0.9% in face. 9.7% presented fever and arthromyialgias, especially in young people (p < 0.05). The etiopathogenic factors implied were tuberculosis, streptococcic pharyngoamygdalitis, sarcoidosis and different drugs. The most frequent histological pattern was septal panniculitis without vasculitis. 24.8% did not realize any treatment; 32.5% took nonsteroideal anti-inflammatory drugs; 31.6% potassium iodide; 16% systemic corticosteroids and 7.1% tuberculostatic drugs. Evolution of the patients was good and independently from the treatment performed. CONCLUSIONS: Panniculitides are a group of diseases with similar clinic, but very heterogeneous in their etiology and histopathologic findings. They are more frequent in women and with more expressive clinic in young people. Up to in the 59.3% of the studied cases a causal etiologic agent was identified. These factors are compatible with the published ones in other previous panniculitis series. When a paniculitis is suspected, the most efficient tool is the clinical diagnosis. Histological confirmation by cutaneous biopsy it must be done when it is possible.

Paniculitis subcutáneas en un hospital de tercer nivel: estudio retrospectivo de 113 casos / Subcutaneous panniculitis at a third level hospital: retrospective study of 113 cases

Introducción: Las paniculitis o hipodermitis son un amplio y heterogéneo grupo de enfermedades caracterizadas por la presencia de nódulos subcutáneos inflamatorios localizados habitualmente en miembros inferiores. Objetivos: Reflejar las características clínicopatológicas de los casos diagnosticados como paniculitis durante un periodo de 5 años; estudio epidemiológico de los pacientes, factores etiopatogénicos, evolución y tratamiento. Material y métodos: Obtuvimos de forma retrospectiva los datos de 113 pacientes diagnosticados de paniculitis mediante informe histopatológico de biopsia cutánea realizadas entre los años 1997 y 2001. Resultados: La proporción entre sexos fue de 4,65 mujeres por cada hombre. La edad media de los pacientes estudiados fue de 49 ± 20 años. El 100 por ciento tuvieron afectación en piernas, el 7,1 por ciento en brazos, el 5,9 por ciento en tronco y el 0,9 por ciento en cara. El 9,7 por ciento presentó fiebre y artromialgias, sobre todo en gente joven (p<0,05). Los factores etiopatogénicos implicados fueron la tuberculosis, la faringoamigdalitis estreptocócica, la sarcoidosis y diversos fármacos. La forma histológica más frecuente fue la paniculitis septal sin vasculitis. El 24,8 por ciento no realizaron tratamiento; el 32,5 por ciento tomaron antiinflamatorios no esteroideos; el 31,6 por ciento yoduro potásico; el 16 por ciento corticoesteroides orales y el 7,1 por ciento tuberculoestáticos. La evolución de los pacientes fue buena en general e independiente del tratamiento realizado. Conclusiones: Las paniculitis son un conjunto de enfermedades con clínica similar, pero muy heterogéneas en cuanto su etiología y hallazgos histopatológicos. Es más frecuente en mujeres y con clínica más expresiva en gente joven. Hasta en el 59,3 por ciento de los casos se halló un agente etiológico causal. Estos factores coinciden con los publicados en otras series anteriores. Ante una sospecha de paniculitis, lo más eficiente es el diagnóstico clínico. Se debe realizar confirmación histológica mediante la realización de biopsia cutánea siempre que sea posible (AU)

Síndrome de Klippel-Trenàunay en el adulto / Klippel-Trenáunay syndrome: and a adult case report

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Púrpura de Schönlein-Henoch y esclerosis tuberosa en el adulto / Adult´s Schölein-Henonch purple and tuberous sclerosis in adults

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[Characteristics of Kaposi's sarcoma. A retrospective study in a reference hospital]. / Características del sarcoma de Kaposi. Estudio retrospectivo en un hospital de Tercer Nivel.

UNLABELLED: Kaposi's angiosarcoma (SK) is a vascular tumour that affects skin and other organs. Nowadays there is thought that immunosuppression is one of the factors related with its genesis. OBJECTIVES: Show the information corresponding to the distribution of the SK, proportion of subtypes, evolution and therapeutic used. MATERIAL AND METHODS: A 28 cases retrospective study. We obtained the personal background, habits, origin of the VIH when the SK was associated with AIDS, and treatment carry out. Type of SK and location, cutaneous presentation, complications and B symptoms. Treatment, response and adverse effects. Progression of the disease, average time of relapse and survival, and presence of the SK at death. RESULTS: 64% epidemic, 21% classic type and 14% associated with transplants. In 48% of the epidemic cases, the VIH assumed to homosexual habits and 18% to being ADVP. In all there was cutaneous affectation, 46% had affectation of mucouses, 11% adenopathies and 14% visceral extension. 71% received treatment: 40% chemotherapy, 35% radiotherapy and 18% cryotherapy. Progression: 11% became stable, in 50% there was local extension and systemic in 17%. The average survival was of 4.16 +/- 3 years. CONCLUSIONS: SK has a minor incidence in the homosexual population. The high proportion of classic and transplants associated affirm the role of immunosuppression as a predisposing factor. There were numerous local complications that were associated with B symptoms. The cryotherapy was used as the first option in the located forms and in the widespread ones was the chemotherapy.

Características del sarcoma de Kaposi. Estudio retrospectivo en un hospital de Tercer Nivel / Characteristics of kaposi´s sarcoma. A retrospective study in a reference hospital

El angiosarcoma de Kaposi (SK) es un tumor vascular que afecta a piel y otros órganos. Actualmente se piensa que en su génesis intervienen factores relacionados con la inmunosupresión. Objetivos: Reflejar los datos correspondientes a la distribución del SK, proporción de subtipos, evolución y terapéutica empleada. Material y métodos: Estudio retrospectivo de 28 casos. Obtuvimos los datos personales, hábitos, origen del VIH cuando el SK estaba asociado a SIDA, y tratamiento realizado. Tipo de SK y localización, presentación cutánea, complicaciones y síntomas B. Tratamiento realizado, respuesta y efectos indeseables del mismo. Progresión de la enfermedad, tiempo medio de recidiva, supervivencia media y presencia del SK al fallecer. Resultados: 64 por ciento epidémicos, 21 por ciento tipo clásico y 14 por ciento asociado a trasplantes. En el 48 por ciento de los casos epidémicos, se atribuyó el VIH a hábitos homosexuales y el 18 por ciento a ser ADVP. En todos hubo afectación cutánea, el 46 por ciento tuvo afectación de mucosas, 11 por ciento adenopatías y 14 por ciento extensión visceral. El 71 por ciento recibió tratamiento: 40 por ciento quimioterapia, 35 por ciento radioterapia y 18 por ciento crioterapia. Progresión: el 11 por ciento se estabilizó, en el 50 por ciento hubo extensión local y sistémica en el 17 por ciento. La supervivencia media fue de 4,16 ñ 3 años. Conclusiones: Hay menor incidencia de SK en la población homosexual. La elevada proporción del clásico y asociado a trasplantes apoya un estado de inmunodepresión como factor predisponente. Hubo numerosas complicaciones locales que se asociaron a síntomas B. La crioterapia se utilizó como primera opción en las formas localizadas y en las generalizadas la quimioterapia (AU)

Kaposi's angiosarcoma (SK) is a vascular tumour that affects skin and other organs. Nowadays there is thought that immunosuppression is one of the factors related with its genesis. Objectives: Show the information corresponding to the distribution of the SK, proportion of subtypes, evolution and therapeutic used. Material and methods: A 28 cases retrospective study. We obtained the personal background, habits, origin of the VIH when the SK was associated with AIDS, and treatment carry out. Type of SK and location, coetaneous presentation, complications and B symptoms. Treatment, response and adverse effects. Progression of the disease, average time of relapse and survival, and presence of the SK at death. Results: 64% epidemic, 21% classic type and 14% associated with transplants. In 48% of the epidemic cases, the VIH assumed to homosexual habits and 18% to being ADVP. In all there was coetaneous affectation, 46% had affectation of mucouses, 11% adenophaties and 14% visceral extension. 71% received treatment: 40% chemotherapy, 35% radiotherapy and 18% criotherapy. Progression: 11% became stable, in 50% there was local extension and systemic in 17%. The average survival was of 4,16±3 years. Conclusions: SK has a minor incidence in the homosexual population. The high proportion of classic and transplants associated affirm the role of inmunosuppression as a predisposing factor. There were numerous local complications that were associated with B symptoms. The criotherapy was used as the first option in the located forms and in the widespread ones was the chemotherapy (AU)

Visual P3 findings in Mission Indian youth: relationship to family history of alcohol dependence and behavioral problems.

Native Americans have some of the highest rates of alcohol abuse and dependence, yet risk factors for problem drinking remain relatively unknown. The amplitude of the P3 component of the event-related potential (ERP) has been suggested to be an index of 'vulnerability to alcoholism', especially when it is elicited by visual tasks in younger individuals. Visual P3 tasks, however, have not been previously investigated in Native American youth. One hundred and four Mission Indian youth between the ages of 7 and 13 years participated in the study. ERPs were collected using two visual target paradigms: a facial discrimination and an estimation of line orientation task. Analyses of covariance revealed that participants with a first degree family history of alcoholism had lower P3 component amplitudes in frontal leads to the facial discrimination task. Lower P3 amplitudes, in posterior areas, were found in the line discrimination task in children who scored above the 75th percentile in delinquent behaviors on the Achenbach Child Behavior Checklist. These findings are consistent with investigations in non-Indian populations demonstrating that the late positive component of the event related potential is sensitive to both familial history of alcohol dependence as well as personal history of externalizing behaviors.

Auditory P3 findings in mission Indian youth.

OBJECTIVE: Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential biological risk factors associated with the problem drinking seen in many tribes remain relatively unknown. In this study, the amplitude of the P3 component of the event-related potential (ERP), a measure associated with risk for alcoholism in European-American youth, was investigated in Mission Indians. METHOD: The study participants were Mission Indian children and adolescents (N = 68, 37 male) between the ages of 7 and 13 years. ERPs were collected using two auditory "oddball" paradigms: an easy and a difficult discrimination task. P3 amplitude and latency were statistically evaluated as a function of age, gender, degree of Native American heritage (NAH) and family history (FH) of alcohol dependence. RESULTS: P3 latency was found to vary as a function of age and gender, with girls demonstrating greater decreases in latency with age than boys. suggesting a faster maturation time. Whereas there were no significant relationships between NAH and P3 latency, those participants with at least one alcoholic parent had longer P3 latencies elicited by the difficult auditory task. No significant relationships were found between P3 amplitude generated to the target tones and any of the variables (age, gender, FH, NAH). CONCLUSIONS: Mean P3 amplitudes and latencies obtained from these Mission Indian youth were within the range of those values reported in the literature for samples of children and adolescents of other ethnicities. Although the amplitude of the P3 ERP measure has been associated with FH of alcoholism in studies of predominantly European-American individuals, P3 amplitudes generated in response to these auditory tasks did not robustly differentiate Mission Indian children and adolescents who may be at higher risk for alcoholism from those presumed to be at lower risk.

EEG asymmetry: relationship to mood and risk for alcoholism in Mission Indian youth.

BACKGROUND: Left frontal electroencephalogram (EEG) alpha dominance has been hypothesized to be related to depressed mood as well as aversive motivation and emotion. However, few studies have prospectively evaluated electroencephalogram asymmetry during development in high-risk adolescents and children. METHODS: EEG alpha asymmetry was investigated in 134 Mission Indian children who were between 7 and 13 years of age. The relationships between electroencephalogram alpha asymmetry and age, gender, parental history of alcohol dependence, Native American heritage, and mood/ approach behaviors were explored. RESULTS: No significant relationship was found between frontal alpha asymmetry and age, gender, or behavioral measures of depressed mood and/or approach behaviors. However, participants with > or = 50% Native American heritage were significantly more likely to have greater electroencephalogram alpha power in the left frontal cortex than in the right. CONCLUSIONS: The present findings suggest that the hypothesized relationship between EEG alpha asymmetry and measures of depressed mood, aversive motivation, and emotion may not be universal in all age or ethnic groups. Additionally, though the relationship between greater degrees of Native American heritage and alpha asymmetry are not as yet clear, we suggest it may be more related to substance abuse than depression in this population of Mission Indians.

Effects of age and parental history of alcoholism on EEG findings in mission Indian children and adolescents.

BACKGROUND: Many, but not all, Native American tribes have some of the highest rates of alcohol abuse and dependence. Yet, risk factors for the development of problem drinking in these high risk groups remain largely unknown. In primarily Euroamerican populations, electrophysiological variables have been associated with risk for alcoholism. The EEG has a specific developmental time course that has been described in a diverse set of ethnic groups, but it has not been described in Native American youth. In addition, the relationship between EEG development and risk for alcoholism in Indian youth has not been previously studied. METHODS: Clinical ratings and spectral characteristics of the resting EEG were investigated in 140 Native American Mission Indian children and adolescents between the ages of 7 and 13 years. The specific aims of the study were to (1) investigate the relationship of age and gender with EEG spectral variables to determine if this population conforms to similar trends from previously published data in other ethnic groups and (2) to determine whether children with a parental history of alcoholism differ from those without alcoholic parents on EEG spectral parameters. RESULTS: No excess of abnormal EEG activity was found in this sample of Native American youth. Age, but not gender, was found to have a significant effect on EEG spectral characteristics with younger children (7-11 years old), having significantly more power in slow activity (0.5-7.5 Hz) and in alpha power (8-12 Hz) as well as slower alpha frequencies than older children (12-13 years old). Consistent with other studies of Native American youth, 66% of the children and adolescents participating in this study had at least one parent who had a lifetime diagnosis of alcohol dependence. However, an ANCOVA that covaried for age and gender revealed no significant differences in power or frequency characteristics of the EEG on the basis of parental history of alcoholism. CONCLUSIONS: These studies suggest that this sample of Mission Indian children, despite high levels of parental alcohol dependence and low socioeconomic status, show normal EEG development. As yet, no relationship has been found between any specific EEG phenotype and parental history of alcoholism in this population, however, further EEG maturation may be necessary before any relationships can be fully delineated.

Timoma maligno microinfiltrante de localización ectópica cervical / Ectopic microinvasive malignant thymoma in neck

Se presenta el caso de una mujer de 54 años con un timoma maligno microinfiltrante de localización ectópica cervical. El tumor estaba situado por debajo del lóbulo izquierdo del tiroides en la cara anterior del cuello, encapsulado y presentaba un aspecto lobulado al corte. Histológicamente, el tumor estaba formado por una población mixta de linfocitos y células epiteliales con escasa mitosis que infiltraba la cápsula. Se discuten las pautas diagnósticas y terapéuticas en este tipo tumoral (AU)

Parental history of alcoholism and problem behaviors in Native-American children and adolescents.

BACKGROUND: A positive family history of alcoholism is one of the most consistent and powerful predictors of a person's risk for developing this disorder. This finding has stimulated much research on etiological vulnerability factors and mechanisms by which children of alcoholic parents are at high risk for developing alcohol-related problems. In primarily Euro-American samples, parental alcoholism has been associated with a variety of negative outcomes for children and adolescents, including problematic behavior. Native-American Indians, in addition to high rates of alcoholism and alcohol-related mortality, have the highest prevalence of a positive family history for alcoholism of all ethnic groups in the United States. METHODS: This study used the Achenbach Child Behavior Checklist (CBCL) to evaluate behavioral problems in 96 Mission Indian children and adolescents based on the presence or absence of parental alcohol dependence and sex of the offspring. RESULTS: Consistent with previous research, results indicated a high prevalence of a positive family history of alcoholism in these Native-American youths. Seventy-four percent of the offspring had either one or both parents with alcohol dependence (children of alcoholics). Only 7% had no first- or second-degree alcoholic relatives. Results indicated that sons of alcoholics scored significantly higher on the Total Behavior Problem scale, as well as the Internalizing and Externalizing scales, of the CBCL than sons of nonalcoholics, whereas there were no significant differences in CBCL scores between daughters of alcoholics and daughters of nonalcoholics. It is noteworthy that scores on the CBCL for Mission Indian children of alcoholics were comparable to scores in the published literature of children of alcoholics of other ethnicities. In addition, a relatively low percentage of youths were identified with significant levels of behavioral problems. CONCLUSIONS: These findings suggest that sons of alcoholics of Mission Indian heritage experience more problems than sons of nonalcoholics, but also suggest that Mission Indian children of alcoholics are not more vulnerable to behavioral problems than children of alcoholic parents of other ethnic backgrounds.

Absence of point mutations at codon 17 of the mdm2 gene (serine 17) in human primary tumors.

Mdm2 is a phosphoprotein that interacts with protein p53, inhibiting its activity. A serine located in position 17 of Mdm2, has been implicated in its phosphorylation process. We hypothesize that point mutations at serine 17 could block its phosphorylation and thereby increase the p53-Mdm2 interaction. This mechanism could increase the p53 degradation and cause a loss of the protective effect of p53 against tumorigenesis. This hypothesis was based on recent studies in vitro, demonstrating that when serine 17 is mutated, the DNA-dependent protein kinase, activated by genomic damage, is unable to phosphorylate it. Thus, we investigated whether structural point mutations at exon 3 of the Mdm2 gene, affecting codon 17, were present in 162 human primary tumors, 70 breast carcinomas, 14 bladder tumors, 18 colon adenocarcinomas and 60 testicular tumors. Direct sequencing of a fragment (204 bp) of exon 3 of the Mdm2 gene that contains the codon 17 showed no mutations at this position, independently of the presence or absence of p53 gene mutations in the same tumors. These results do not support the hypothesis that mutations in the Mdm2 gene at this level are involved in the tumorigenic process of human cancers.

Electroencephalographic responses to alcohol challenge in Native American Mission Indians.

BACKGROUND: Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential central nervous system risk factors responsible for the problem drinking seen in some tribes remain relatively unknown. METHODS: Background electroencephalographic (EEG) variants and response to alcohol were investigated in 48 Native American Mission Indian men between 18 and 25 years old. RESULTS: Subjects with 50% or greater Native American heritage had a significantly higher proportion of low-voltage EEG variants. Within this sample of Mission Indian men, however, a family history of alcohol dependence was associated with a greater incidence of high voltage alpha EEGs. Mission Indian men also evidenced a "less depressant, more stimulating" response to alcohol as quantified by less alcohol-induced reductions in alpha, greater EEG stability, and increased alcohol-induced beta activity. CONCLUSIONS: These findings demonstrate that certain genetically regulated EEG variants that have been previously associated with risk for alcoholism in Caucasians may also be more common in these Mission Indian men. Additionally, EEG measures of response to alcohol do not provide support for the commonly held idea that Indians are more sensitive to the depressant effects of alcohol.