RESUMEN
The cerebellum has been associated with timing on the millisecond scale and with musical rhythm and beat processing. Early musical training (before age 7) is associated with enhanced rhythm synchronization performance and differences in cortical motor areas and the corpus callosum. In the present study, we examined the relationships between regional cerebellar volumes, early musical training, and timing performance. We tested adult musicians and non-musicians on a standard finger tapping task, and extracted cerebellar gray and white matter volumes using a novel multi-atlas automatic segmentation pipeline. We found that early-trained musicians had reduced volume in bilateral cerebellar white matter and right lobules IV, V and VI, compared to late-trained musicians. Strikingly, better timing performance, greater musical experience and an earlier age of start of musical training were associated with smaller cerebellar volumes. Better timing performance was specifically associated with smaller volumes of right lobule VI. Collectively, these findings support the sensitivity of the cerebellum to the age of initiation of musical training and suggest that lobule VI plays a role in timing. The smaller cerebellar volumes associated with musical training and timing performance may be a reflection of more efficiently implemented low-level timing and sensorimotor processes.
Asunto(s)
Mapeo Encefálico , Cerebelo/anatomía & histología , Actividad Motora/fisiología , Música , Desempeño Psicomotor/fisiología , Adulto , Femenino , Dedos , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
BACKGROUND: Mitral valve-in-valve (ViV) is associated with suboptimal hemodynamics and rare left ventricular outflow tract (LVOT) obstruction. OBJECTIVES: This study aimed to determine whether device position and asymmetry are associated with these outcomes. METHODS: Patients undergoing SAPIEN 3 (Edwards Lifesciences) mitral ViV included in the VIVID (Valve-in-Valve International Data) Registry were studied. Clinical endpoints are reported according to Mitral Valve Academic Research Consortium definitions. Residual mitral valve stenosis was defined as mean gradient ≥5 mm Hg. Depth of implantation (percentage of transcatheter heart valve [THV] atrial to the bioprosthesis ring) and asymmetry (ratio of 2 measures of THV height) were evaluated. RESULTS: A total of 222 patients meeting the criteria for optimal core lab evaluation were studied (age 74 ± 11.6 years; 61.9% female; STS score = 8.3 ± 7.1). Mean asymmetry was 6.2% ± 4.4%. Mean depth of implantation was 19.0% ± 10.3% atrial. Residual stenosis was common (50%; mean gradient 5.0 ± 2.6 mm Hg). LVOT obstruction occurred in 7 cases (3.2%). Implantation depth was not a predictor of residual stenosis (OR: 1.19 [95% CI: 0.92-1.55]; P = 0.184), but more atrial implantation was protective against LVOT obstruction (0.7% vs 7.1%; P = 0.009; per 10% atrial, OR: 0.48 [95% CI: 0.24-0.98]; P = 0.044). Asymmetry was found to be an independent predictor of residual stenosis (per 10% increase, OR: 2.30 [95% CI: 1.10-4.82]; P = 0.027). CONCLUSIONS: Valve stenosis is common after mitral ViV. Asymmetry was associated with residual stenosis. Depth of implantation on its own was not associated with residual stenosis but was associated with LVOT obstruction. Technical considerations to reduce postdeployment THV asymmetry should be considered.
Asunto(s)
Fibrilación Atrial , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Constricción Patológica/etiología , Resultado del Tratamiento , Cateterismo Cardíaco/efectos adversos , Hemodinámica , Sistema de Registros , Diseño de PrótesisRESUMEN
This review on the benefits of pulsatile flow includes not only experimental and clinical data, but also attempts to further illuminate the major factors as to why this debate has continued during the past 55 years. Every single component of the cardiopulmonary bypass (CPB) circuitry is equally important for generating adequate quality of pulsatility, not only the pump. Therefore, translational research is a necessity to select the best components for the circuit. Generation of pulsatile flow depends on an energy gradient; precise quantification in terms of hemodynamic energy levels is, therefore, a necessity, not an option. Comparisons between perfusion modes should be done after these basic steps have been taken. We have also included experimental and clinical data for direct comparisons between the perfusion modes. In addition, we included several suggestions for future clinical trials for other interested investigators.
Asunto(s)
Puente Cardiopulmonar/métodos , Hemodinámica , Flujo Pulsátil , Adolescente , Puente Cardiopulmonar/efectos adversos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Investigación Biomédica Traslacional/métodosRESUMEN
Some individuals identified as being at clinical high risk (CHR) for developing psychosis may suffer substantial anxiety due to a fear of transitioning to psychosis. This can be associated with catastrophic misinterpretation of normal mental experiences, such as a momentary lapse in attention, as markers for psychosis, fueled by hypervigilance for mental experiences that may be perceived as signs of impending psychosis. This anxiety may only worsen due to the self-stigma triggered by admission to a psychiatric CHR clinic, independent of whether or not the individual transitions to psychosis. Based on a clinical case study, we propose a cognitive model for this anxiety, an extension of Clark's model of panic. Our model accounts for causal factors of this distress, such as self-stigma and maladaptive core beliefs. It also includes maintaining factors such as hypervigilance for mental experiences and catastrophic misinterpretation of normal mental experiences as anomalous and portending eventual psychosis. We outline assessment and treatment guidelines and offer suggestions for how this model could be empirically validated. We suggest that treatment with this model, under the neural diathesis-stress framework, may have the potential to lower the risk of transition to psychosis and that assessment for such anxiety should be part of standard CHR care.
Asunto(s)
Ansiedad/psicología , Terapia Cognitivo-Conductual , Síntomas Prodrómicos , Trastornos Psicóticos/psicología , Estigma Social , Ansiedad/terapia , Progresión de la Enfermedad , Femenino , Humanos , Modelos Psicológicos , Trastornos Psicóticos/prevención & control , Riesgo , Autoimagen , Adulto JovenRESUMEN
The effect of potassium administration and of dietary potassium deprivation on plasma renin activity and aldosterone excretion has been studied in 10 normal subjects and in 12 hypertensive patients maintained on a constant dietary regimen. Potassium administration reduced plasma renin activity in 18 of 28 studies of both normal and hypertensive subjects. Suppression of renin often occurred despite sodium diuresis induced by potassium administration. The renin suppression was related to induced changes in plasma potassium concentration and urinary potassium excretion. The failure of suppression of plasma renin in 10 studies could be accounted for by the smaller amounts of potassium administered to these subjects, together with a possibly overriding influence of an induced sodium diuresis. In six studies potassium deprivation invariably increased plasma renin activity even though a tendency for sodium retention often accompanied this procedure. The data indicate that both the suppression of plasma renin activity induced by potassium administration and the stimulation of renin activity which follows potassium depletion occur independently of associated changes in either aldosterone secretion or in sodium balance. However, the results do suggest that in various situations, the influence of potassium on plasma renin activity may be either amplified or preempted by changes in sodium balance. These interactions between potassium and plasma renin could be mediated by an ill-defined extrarenal pathway. But the findings are more consistent with an intrarenal action of potassium ions to modify renin release. Potassium might modify renin secretion directly by acting on the juxtaglomerular cells or by a change in its tubular reabsorption or secretion. The effects of potassium ions on renin secretion might also be mediated indirectly via an induced change in tubular sodium transport.
Asunto(s)
Aldosterona/metabolismo , Hipertensión/metabolismo , Riñón/metabolismo , Deficiencia de Potasio/metabolismo , Potasio/metabolismo , Renina/metabolismo , Adulto , Angiotensina II/metabolismo , Transporte Biológico Activo , Presión Sanguínea , Dietoterapia , Femenino , Humanos , Hipertensión/terapia , Aparato Yuxtaglomerular/metabolismo , Masculino , Persona de Mediana Edad , Natriuresis , Potasio/administración & dosificación , Sodio/metabolismoRESUMEN
We used the Structured Interview for DSM-III Personality Disorders to diagnose DSM-III personality disorders systematically in 55 patients with obsessive-compulsive disorder in the active-treatment cell of a controlled trial of clomipramine hydrochloride. Patients with a cluster A personality disorder had significantly higher obsessive-compulsive disorder severity scores at baseline, and the number of personality disorders was strongly related to baseline severity of obsessive-compulsive disorder symptoms. At the conclusion of the 12-week study, we found no significant difference in treatment outcome with clomipramine between those patients with at least one personality disorder and those with no personality disorders. However, the presence of schizotypal, borderline, and avoidant personality disorders, along with total number of personality disorders, did predict poorer treatment outcome. These variables were strongly related to having at least one cluster A personality disorder diagnosis, which was also a strong predictor of poorer outcome. Implications of these findings are discussed.
Asunto(s)
Clomipramina/uso terapéutico , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastornos de la Personalidad/diagnóstico , Adulto , Análisis de Varianza , Método Doble Ciego , Femenino , Humanos , Masculino , Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/diagnóstico , Trastornos de la Personalidad/clasificación , Trastornos de la Personalidad/complicaciones , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Índice de Severidad de la Enfermedad , Terminología como Asunto , Resultado del TratamientoRESUMEN
We assessed 96 patients with obsessive-compulsive disorder for DSM-III personality disorder diagnoses with a standardized interview instrument (Structured Interview for the DSM-III Personality Disorders). Fifty patients (52%) met criteria for at least one personality disorder, with mixed, dependent, and histrionic personality disorders most frequently diagnosed. Compulsive personality disorder was diagnosed in only 6 patients (6%), 5 of whom had had onset of obsessive-compulsive symptoms before the age of 10 years, indicating that DSM-III compulsive personality disorder is not invariably a premorbid condition for the development of obsessive-compulsive disorder. Schizotypal personality disorder, at 5%, was found to be less common than in past samples, reflecting differences in either assessment methods or sampling.
Asunto(s)
Trastorno Obsesivo Compulsivo/complicaciones , Trastornos de la Personalidad/diagnóstico , Adolescente , Adulto , Anciano , Boston/epidemiología , Trastorno de Personalidad Compulsiva/complicaciones , Trastorno de Personalidad Compulsiva/diagnóstico , Trastorno de Personalidad Compulsiva/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Determinación de la Personalidad , Trastornos de la Personalidad/complicaciones , Trastornos de la Personalidad/epidemiología , Escalas de Valoración Psiquiátrica , Trastorno de la Personalidad Esquizotípica/complicaciones , Trastorno de la Personalidad Esquizotípica/diagnóstico , Trastorno de la Personalidad Esquizotípica/epidemiologíaRESUMEN
To evaluate the feasibility of cingulotomy as a treatment for patients with intractable obsessive-compulsive disorder, we evaluated the records of all 35 patients with this diagnosis who had undergone one or more such procedures at Massachusetts General Hospital, Boston, during the last 25 years. Retrospectively, all but two of these patients met DSM-III-R criteria for obsessive-compulsive disorder. Six patients were deceased; four by suicide. Questionnaires were sent to the remaining 27 patients with obsessive-compulsive disorder; 17 patients returned the questionnaire and another agreed to an interview without completing the forms. Sixteen of these 18 patients participated in a telephone interview, and patient reports were corroborated by an informant in 10 cases. Despite the presence of some side effects, such as easily controlled seizures (9%) and transient mania (6%), the results of this investigation support the use of cingulotomy as a potentially effective treatment for patients with severe and disabling obsessive-compulsive disorder. With the use of very conservative criteria, we estimated that at least 25% to 30% of the patients benefited substantially from this procedure. Similar results were found in a preliminary prospective study of four patients who recently underwent cingulotomy after state-of-the-art preoperative treatments had failed.
Asunto(s)
Giro del Cíngulo/cirugía , Trastorno Obsesivo Compulsivo/cirugía , Psicocirugía , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Trastornos Mentales/complicaciones , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/terapia , Escalas de Valoración Psiquiátrica , Psicoterapia , Psicotrópicos/uso terapéutico , Técnicas EstereotáxicasRESUMEN
BACKGROUND: The study was designed to determine the mediating neuroanatomy of obsessive-compulsive disorder (OCD). METHODS: The short half-life tracer oxygen 15-labeled carbon dioxide was used to allow for repeated positron emission tomographic determinations of regional cerebral blood flow on each of eight patients with OCD during a resting and a provoked (symptomatic) state. RESULTS: Individually tailored provocative stimuli were successful in provoking OCD symptoms, in comparison with paired innocuous stimuli, as measured by self-report on OCD analogue scales (P = .002). Omnibus subtraction images demonstrated a statistically significant increase in relative regional cerebral blood flow during the OCD symptomatic state vs the resting state in right caudate nucleus (P < .006), left anterior cingulate cortex (P < .045), and bilateral orbitofrontal cortex (P < .008); increases in the left thalamus approached but did not reach statistical significance (P = .07). CONCLUSIONS: These findings are consistent with results of previous functional neuroimaging studies and contemporary neurocircuitry models of OCD. The data further implicate orbitofrontal cortex, caudate nucleus, and anterior cingulate cortex in the pathophysiology of OCD and in mediating OCD symptoms.
Asunto(s)
Encéfalo/diagnóstico por imagen , Dióxido de Carbono , Circulación Cerebrovascular , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Radioisótopos de Oxígeno , Tomografía Computarizada de Emisión , Adulto , Encéfalo/fisiopatología , Núcleo Caudado/irrigación sanguínea , Femenino , Lóbulo Frontal/irrigación sanguínea , Giro del Cíngulo/irrigación sanguínea , Humanos , Masculino , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/fisiopatología , Tálamo/irrigación sanguíneaRESUMEN
BACKGROUND: Schizophrenia has been hypothesized to be caused by a hypofunction of glutamatergic neurons. Findings of reduced concentrations of glutamate in the cerebrospinal fluid of patients with schizophrenia and the ability of glutamate-receptor antagonists to cause psychotic symptoms lend support to this hypothesis. N-acetylaspartylglutamate (NAAG), a neuropeptide that is highly concentrated in glutamatergic neurons, antagonizes the effects of glutamate at N-methyl-D-aspartate receptors. Moreover, NAAG is cleaved to glutamate and N-acetylaspartate by a specific peptidase, N-acetyl-alpha-linked acidic dipeptidase (NAALADase). To test the glutamatergic hypothesis of schizophrenia, we studied the NAAG-related glutamatergic variables in postmortem brains from patients with schizophrenia, neuroleptic-treated controls, and normal individuals, with particular emphasis on the prefrontal cortex and hippocampus. METHOD: Different regions of frozen brain tissue from three different groups (patients with schizophrenia, neuroleptic-treated controls, and normal controls) were assayed to determine levels of NAAG, N-acetylaspartate, NAALADase, and several amino acids, including aspartate and glutamate. RESULTS: Our study demonstrates alterations in brain levels of aspartate, glutamate, and NAAG and in NAALADase activity. Levels of NAAG were increased and NAALADase activity and glutamate levels were decreased in the schizophrenic brains. Notably, the changes in NAAG level and NAALADase activity in schizophrenic brains were more selective than those for aspartate and glutamate. In neuroleptic-treated control brains, levels of aspartate, glutamate, and glycine were found to be increased. CONCLUSIONS: The changes in levels of aspartate, glutamate, NAAG, and NAALADase are prominent in the prefrontal and hippocampal regions, where previous neuropathological studies of schizophrenic brains demonstrate consistent changes. These findings support the hypothesis that schizophrenia results from a hypofunction of certain glutamatergic neuronal systems. They also suggest that the therapeutic efficacy of neuroleptics may be related to increased glutamatergic activity.
Asunto(s)
Antígenos de Superficie , Encéfalo/metabolismo , Glutamatos/metabolismo , Receptores de Glutamato/metabolismo , Esquizofrenia/metabolismo , Adulto , Anciano , Encéfalo/enzimología , Encéfalo/fisiología , Dipeptidasas/metabolismo , Dipeptidasas/fisiología , Dipéptidos/metabolismo , Dipéptidos/fisiología , Femenino , Glutamato Carboxipeptidasa II , Hipocampo/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Corteza Prefrontal/metabolismo , Receptores de Glutamato/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/fisiopatologíaRESUMEN
BACKGROUND: The purpose of this study was to assess prospectively long-term change in obsessive-compulsive disorder (OCD) symptoms in patients with an OCD diagnosis that was confirmed by structured interview and with documented unsuccessful trials of multiple medications and attempts at behavior therapy. METHODS: We conducted an unblinded preoperative and follow-up assessment of comorbid diagnosis; OCD, depressive, and anxiety symptoms; and functional status in 18 patients who underwent cingulotomy. RESULTS: At a mean follow-up of 26.8 months, five patients (28%) met conservative criteria for treatment responders, and three others (17%) were partial responders. The group improved significantly in mean functional status, and few serious adverse events were found. Improvement in OCD symptoms was strongly correlated with improvement in depressive and anxiety symptoms. CONCLUSIONS: The rate of clinical improvement was consistent with a previous retrospective study in the same setting, indicating that 25% to 30% of the patients who previously were unresponsive to medication and behavioral treatments are significantly improved after cingulotomy. Cingulotomy remains a last resort treatment for severely incapacitated patients who have not responded to all other state-of-the-art pharmacological and behavioral treatments for OCD and is not to be taken lightly.
Asunto(s)
Giro del Cíngulo/cirugía , Trastorno Obsesivo Compulsivo/cirugía , Psicocirugía , Adulto , Edad de Inicio , Anciano , Terapia Conductista , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/psicología , Trastorno Obsesivo Compulsivo/terapia , Probabilidad , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Calidad de Vida , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Perfil de Impacto de Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: The goal of this study was to determine the mediating neuroanatomy of simple phobic symptoms. METHODS: Positron emission tomography and oxygen 15 were used to measure normalized regional cerebral blood flow in seven subjects with simple phobia during control and provoked states. Stereotactic transformation and statistical parametric mapping techniques were employed to determine the locations of significant activation. RESULTS: Statistical parametric maps demonstrated significant increases in normalized regional blood flow for the symptomatic state compared with the control state in the anterior cingulate cortex, the insular cortex, the anterior temporal cortex, the somatosensory cortex, the posterior medial orbitofrontal cortex, and the thalamus. CONCLUSIONS: The results suggest that anxiety associated with the simple phobic symptomatic state is mediated by paralimbic structures. Moreover, activation of somatosensory cortex may reflect tactile imagery as one component of the phobic symptomatic condition.
Asunto(s)
Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular , Trastornos Fóbicos/diagnóstico por imagen , Tomografía Computarizada de Emisión , Adulto , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/diagnóstico por imagen , Femenino , Giro del Cíngulo/irrigación sanguínea , Giro del Cíngulo/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Radioisótopos de Oxígeno , Trastornos Fóbicos/diagnóstico , Trastornos Fóbicos/psicología , Corteza Somatosensorial/irrigación sanguínea , Corteza Somatosensorial/diagnóstico por imagen , Tálamo/irrigación sanguínea , Tálamo/diagnóstico por imagen , Tacto/fisiologíaRESUMEN
BACKGROUND: A previous pilot study of only posterior brain regions found lower white-matter volume in patients with obsessive-compulsive disorder than in normal control subjects. We used new cohorts of patients and matched normal control subjects to study whole-brain volume differences between these groups with magnetic resonance imaging-based morphometry. METHODS: Ten female patients with obsessive-compulsive disorder and 10 female control subjects, matched for handedness, age, weight, education, and verbal IQ, underwent magnetic resonance imaging with a 3-dimensional volumetric protocol. Scans were blindly normalized and segmented by means of well-characterized semiautomated intensity contour mapping and differential intensity contour algorithms. Brain structures investigated included the cerebral hemispheres, cerebral cortex, diencephalon, caudate, putamen, globus pallidus, hippocampus amygdala, third and fourth ventricles, corpus callosum, operculum, cerebellum, and brain stem. Anterior to posterior neocortical regions, including precallosum, anterior pericallosum, posterior pericallosum, and retrocallosum, with adjacent white matter were also measured. Volumes found different between groups were correlated with Yale-Brown Obsessive Compulsive Scale score and Rey-Osterieth Complex Figure Test measures. RESULTS: Confirming results of our earlier pilot study and expanding the findings to the whole brain, patients with obsessive-compulsive disorder had significantly less total white matter but, in addition, significantly greater total cortex and opercular volumes. Severity of obsessive-compulsive disorder and nonverbal immediate memory correlated with opercular volume. CONCLUSIONS: Replication of volumetric white-matter differences suggests a widely distributed structural brain abnormality in obsessive-compulsive disorder. Whereas determining the etiogenesis may require research at a microscopic level, understanding its functional significance can be further explored via functional neuroimaging and neuropsychological studies.
Asunto(s)
Encéfalo/anatomía & histología , Imagen por Resonancia Magnética , Trastorno Obsesivo Compulsivo/diagnóstico , Adulto , Núcleo Caudado/anatomía & histología , Cuerpo Calloso/anatomía & histología , Femenino , Lateralidad Funcional , Humanos , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. METHODS: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. RESULTS: Statistical maps (nonparametric; P < 10(-3)) showed activation for 70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects exhibited activation in any brain region. CONCLUSIONS: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study.
Asunto(s)
Encéfalo/anatomía & histología , Imagen por Resonancia Magnética/estadística & datos numéricos , Trastorno Obsesivo Compulsivo/diagnóstico , Adulto , Afecto/fisiología , Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Humanos , Sistema Límbico/irrigación sanguínea , Sistema Límbico/fisiología , Angiografía por Resonancia Magnética/estadística & datos numéricos , Modelos Estadísticos , Trastorno Obsesivo Compulsivo/etiología , Trastorno Obsesivo Compulsivo/psicología , Flujo Sanguíneo Regional , Estadística como Asunto , Tomografía Computarizada de Emisión , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Molecular subtypes of breast cancer are characterized by distinct patterns of gene expression that are predictive of outcome and response to therapy. The luminal breast cancer subtypes are defined by the expression of estrogen receptor-alpha (ERα)-associated genes, many of which are directly responsive to the transcription factor activator protein 2C (TFAP2C). TFAP2C participates in a gene regulatory network controlling cell growth and differentiation during ectodermal development and regulating ESR1/ERα and other luminal cell-associated genes in breast cancer. TFAP2C has been established as a prognostic factor in human breast cancer, however, its role in the establishment and maintenance of the luminal cell phenotype during carcinogenesis and mammary gland development have remained elusive. Herein, we demonstrate a critical role for TFAP2C in maintaining the luminal phenotype in human breast cancer and in influencing the luminal cell phenotype during normal mammary development. Knockdown of TFAP2C in luminal breast carcinoma cells induced epithelial-mesenchymal transition with morphological and phenotypic changes characterized by a loss of luminal-associated gene expression and a concomitant gain of basal-associated gene expression. Conditional knockout of the mouse homolog of TFAP2C, Tcfap2c, in mouse mammary epithelium driven by MMTV-Cre promoted aberrant growth of the mammary tree leading to a reduction in the CD24(hi)/CD49f(mid) luminal cell population and concomitant gain of the CD24(mid)/CD49f(hi) basal cell population at maturity. Our results establish TFAP2C as a key transcriptional regulator for maintaining the luminal phenotype in human breast carcinoma. Furthermore, Tcfap2c influences development of the luminal cell type during mammary development. The data suggest that TFAP2C has an important role in regulated luminal-specific genes and may be a viable therapeutic target in breast cancer.
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Neoplasias de la Mama/etiología , Mama/crecimiento & desarrollo , Factor de Transcripción AP-2/fisiología , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Antígeno CD24/análisis , Carcinogénesis , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Femenino , Humanos , Receptores de Hialuranos/análisis , Ratones , Ratones Noqueados , Células Madre Neoplásicas/química , Fenotipo , Factor de Transcripción AP-2/análisisRESUMEN
OBJECTIVE: To test the efficacy of reaction time (RT) measures as a screening test for AIDS dementia complex (ADC). DESIGN AND METHODS: Forty-two patients with mild-to-moderate ADC and 33 healthy HIV-1-seronegative control subjects took a computer-administered battery of four RT measures: simple RT, choice RT, and two types of sequential RT (1 and 2). RESULTS: The performance of the ADC group was significantly worse than that of the control group on all four RT measures, but not all tasks were equally sensitive. The two tests of sequential RT were found to be the best discriminators, and receiver operating characteristic curves analyses indicated that the optimal cut-off z score was 1.0 for both tests. CONCLUSIONS: These preliminary results suggest that computer-based RT, using these two measures of sequential RT, may provide a sensitive method of detecting HIV-1-associated cognitive deficits.
Asunto(s)
Complejo SIDA Demencia/diagnóstico , VIH-1 , Pruebas Neuropsicológicas , Tiempo de Reacción , Complejo SIDA Demencia/fisiopatología , Complejo SIDA Demencia/psicología , Adulto , Anciano , Computadores , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Sensibilidad y EspecificidadRESUMEN
A 36-yr-old woman with a chronic wasting illness associated with hyponatremia and hypotension proved to have secondary adrenal insufficiency and low levels of GH and PRL. TSH, LH, and FSH responses remained normal. Aldosterone excretion was markedly reduced (0.74 microgram/day) before replacement therapy was started, but normal renin and aldosterone responses to sodium restriction were observed after 6 months of corticosteroid treatment. These responses were maintained after acute steroid withdrawal despite the continued absence of ACTH. Chronically adequate glucocorticoid levels were necessary to maintain a normal aldosterone response in this patient. If there is also a pituitary factor required for this response, it does not appear to be ACTH.
Asunto(s)
Hormona Adrenocorticotrópica/deficiencia , Aldosterona/sangre , Dexametasona/uso terapéutico , Fludrocortisona/uso terapéutico , Hiponatremia/tratamiento farmacológico , Hormona Adrenocorticotrópica/sangre , Adulto , Glucemia/análisis , Femenino , Hormona Folículo Estimulante/sangre , Hormona del Crecimiento/sangre , Humanos , Hipoglucemia/sangre , Hiponatremia/sangre , Insulina , Hormona Luteinizante/sangre , Prolactina/sangre , Sodio/sangre , Tirotropina/sangre , VasopresinasRESUMEN
This study used visual and auditory evoked potentials (VEP and AEP) to study low-level sensory processing in a group of 15 unmedicated subjects with obsessive-compulsive disorder (OCD) and 30 age-matched, gender-matched, and handedness-matched normal controls. EPs were recorded to flash (VEP) and binaural click (AEP) stimulation. OCD subjects were found to have significantly shorter latencies on N1 and P2 of the AEP, and no differences were found in the VEP. Results indicate abnormal information processing states in OCD during low-level auditory processing, but not during low-level visual processing. Neural generators of the VEP and AEP are briefly reviewed and results are discussed in relation to current neurobiological models of OCD.
Asunto(s)
Potenciales Evocados Auditivos , Potenciales Evocados Visuales , Trastorno Obsesivo Compulsivo/psicología , Trastornos de la Percepción/diagnóstico , Trastornos de la Percepción/etiología , Estimulación Acústica , Adulto , Encéfalo/fisiopatología , Estimulación Eléctrica , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/fisiopatología , Trastornos de la Percepción/fisiopatologíaRESUMEN
BACKGROUND: Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. METHODS: We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. RESULTS: OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. CONCLUSIONS: Immediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.