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1.
BMC Psychiatry ; 24(1): 23, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38177999

RESUMEN

BACKGROUND: Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design. METHODS: We aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N-of-1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants' natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N-of-1 trials. DISCUSSION: These N-of-1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level. TRIAL REGISTRATION: EudraCT: 2021-003250-23, registered 25 August 2022, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL .


Asunto(s)
Trastorno del Espectro Autista , Cannabidiol , Síndrome del Cromosoma X Frágil , Mucopolisacaridosis , Esclerosis Tuberosa , Humanos , Cannabidiol/uso terapéutico , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/tratamiento farmacológico , Trastorno del Espectro Autista/tratamiento farmacológico , Calidad de Vida , Resultado del Tratamiento , Mucopolisacaridosis/inducido químicamente , Mucopolisacaridosis/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
Tijdschr Psychiatr ; 62(3): 229-233, 2020.
Artículo en Holandés | MEDLINE | ID: mdl-32207133

RESUMEN

The 22q11.2 deletion syndrome (22q11.2ds) is a genetic syndrome affecting multiple organ systems and is associated with increased risk of developing neuropsychiatric disorders. We describe a 15-year old female adolescent with 22q11.2ds, psychotic disorder, and catatonia. Individuals with 22q11.2ds are at increased risk of developing catatonia. Vulnerability for developing extrapyramidal symptoms and epileptic seizures may complicate pharmacological treatment for psychotic episodes. There may be a diagnostic delay of diagnosing Parkinson's disease in patients taking antipsychotics as parkinsonism may be viewed as a side effect. Health professionals working with people with 22q11.2ds should be aware of the increased prevalence of movement disorders and the threshold for referral to 22q11.2ds specialist services should be low.


Asunto(s)
Catatonia , Síndrome de DiGeorge , Trastornos del Movimiento , Trastornos Psicóticos , Adolescente , Diagnóstico Tardío , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/psicología , Femenino , Humanos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/genética
3.
Psychol Med ; 49(6): 1047-1054, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30064532

RESUMEN

BACKGROUND: Identifying factors that influence the functional outcome is an important goal in schizophrenia research. The 22q11.2 deletion syndrome (22q11DS) is a unique genetic model with high risk (20-25%) for schizophrenia. This study aimed to identify potentially targetable domains of neurocognitive functioning associated with functional outcome in adults with 22q11DS. METHODS: We used comprehensive neurocognitive test data available for 99 adults with 22q11DS (n = 43 with schizophrenia) and principal component analysis to derive four domains of neurocognition (Verbal Memory, Visual and Logical Memory, Motor Performance, and Executive Performance). We then investigated the association of these neurocognitive domains with adaptive functioning using Vineland Adaptive Behavior Scales data and a linear regression model that accounted for the effects of schizophrenia status and overall intellectual level. RESULTS: The regression model explained 46.8% of the variance in functional outcome (p < 0.0001). Executive Performance was significantly associated with functional outcome (p = 0.048). Age and schizophrenia were also significant factors. The effects of Executive Performance on functioning did not significantly differ between those with and without psychotic illness. CONCLUSION: The findings provide the impetus for further studies to examine the potential of directed (early) interventions targeting Executive Performance to improve long-term adaptive functional outcome in individuals with, or at high risk for, schizophrenia. Moreover, the neurocognitive test profiles may benefit caregivers and clinicians by providing insight into the relative strengths and weaknesses of individuals with 22q11DS, with and without psychotic illness.


Asunto(s)
Adaptación Psicológica , Cognición , Esquizofrenia/genética , Psicología del Esquizofrénico , Adulto , Síndrome de DiGeorge/psicología , Femenino , Humanos , Masculino , Modelos Genéticos , Pruebas Neuropsicológicas , Factores de Riesgo , Adulto Joven
4.
Tijdschr Psychiatr ; 61(11): 773-778, 2019.
Artículo en Holandés | MEDLINE | ID: mdl-31907887

RESUMEN

BACKGROUND: People with intellectual disability (id) frequently suffer from somatic and psychiatric comorbidity. Somatic morbidity can be the cause and the result of mental health problems. Timely diagnosis and interdisciplinary management are essential for optimal health, development and quality of life.
AIM: To improve interdisciplinary cooperation of professionals involved in care for patients with id, with emphasis on prevalence, diagnosis, and treatment of somatic comorbidity.
METHOD: Literature review and expert opinion.
RESULTS: Epidemiology, diagnostics, and treatment of somatic comorbidity in patients with id are discussed. Additionally, roles and responsibilities of involved professionals are addressed.
CONCLUSION: Somatic comorbidity is highly prevalent in patients with id. People with id should be regularly screened for somatic comorbidity, and re-evaluated in case of behavioral changes. Where available, an id physician can be included in the interdisciplinary care team.


Asunto(s)
Discapacidad Intelectual/epidemiología , Trastornos Mentales/epidemiología , Adulto , Niño , Comorbilidad , Humanos , Discapacidad Intelectual/diagnóstico , Trastornos Mentales/diagnóstico , Salud Mental , Calidad de Vida
6.
Psychol Med ; 47(16): 2854-2865, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28552082

RESUMEN

BACKGROUND: Phenylketonuria (PKU), a genetic metabolic disorder that is characterized by the inability to convert phenylalanine to tyrosine, leads to severe intellectual disability and other cerebral complications if left untreated. Dietary treatment, initiated soon after birth, prevents most brain-related complications. A leading hypothesis postulates that a shortage of brain monoamines may be associated with neurocognitive deficits that are observable even in early-treated PKU. However, there is a paucity of evidence as yet for this hypothesis. METHODS: We therefore assessed in vivo striatal dopamine D2/3 receptor (D2/3R) availability and plasma monoamine metabolite levels together with measures of impulsivity and executive functioning in 18 adults with PKU and average intellect (31.2 ± 7.4 years, nine females), most of whom were early and continuously treated. Comparison data from 12 healthy controls that did not differ in gender and age were available. RESULTS: Mean D2/3R availability was significantly higher (13%; p = 0.032) in the PKU group (n = 15) than in the controls, which may reflect reduced synaptic brain dopamine levels in PKU. The PKU group had lower plasma levels of homovanillic acid (p < 0.001) and 3-methoxy-4-hydroxy-phenylglycol (p < 0.0001), the predominant metabolites of dopamine and norepinephrine, respectively. Self-reported impulsivity levels were significantly higher in the PKU group compared with healthy controls (p = 0.033). Within the PKU group, D2/3R availability showed a positive correlation with both impulsivity (r = 0.72, p = 0.003) and the error rate during a cognitive flexibility task (r = 0.59, p = 0.020). CONCLUSIONS: These findings provide further support for the hypothesis that executive functioning deficits in treated adult PKU may be associated with cerebral dopamine deficiency.


Asunto(s)
Monoaminas Biogénicas/sangre , Encéfalo/metabolismo , Trastornos del Conocimiento/sangre , Dopamina/deficiencia , Fenilcetonurias/psicología , Adolescente , Adulto , Estudios de Casos y Controles , Cognición , Trastornos del Conocimiento/etiología , Función Ejecutiva , Femenino , Humanos , Conducta Impulsiva , Estudios Longitudinales , Masculino , Pruebas Neuropsicológicas , Fenilalanina/sangre , Fenilcetonurias/sangre , Fenilcetonurias/complicaciones , Receptores de Dopamina D2/metabolismo , Adulto Joven
7.
Psychol Med ; 46(11): 2299-311, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27193339

RESUMEN

BACKGROUND: Patients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors. METHOD: Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC. RESULTS: Compared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA. CONCLUSIONS: UHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.


Asunto(s)
Síndrome de DiGeorge/patología , Imagen por Resonancia Magnética/métodos , Trastornos Psicóticos/patología , Sustancia Blanca/patología , Adulto , Síndrome de DiGeorge/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Masculino , Trastornos Psicóticos/diagnóstico por imagen , Riesgo , Sustancia Blanca/diagnóstico por imagen , Adulto Joven
8.
Pharmacopsychiatry ; 48(6): 219-20, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26091278

RESUMEN

In their recent article in Pharmacopsychiatry Verhoeven and Egger report a case series of 28 patients and state that "treatment of psychotic symptoms in patients with 22q11.2 deletion syndrome (22q11.2DS) with quetiapine or clozapine in combination with valproic acid appears likely to be more effective than with other psychotropic compounds". In this letter, we discuss the limitations of their case series and the lack of evidence for such a sweeping conclusion. In lieu of strong evidence to the contrary, standard pharmacological treatments of psychotic illness in 22q11.2DS remains recommended, with attention to 22q11.2DS-related issues. The latter would include management strategies to help ameliorate the elevated risk of seizures (e. g. when using clozapine), and vigilance for Parkinson's disease or other potential movement disorders.


Asunto(s)
Síndrome de Deleción 22q11/complicaciones , Antipsicóticos/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/etiología , Femenino , Humanos , Masculino
9.
Orphanet J Rare Dis ; 16(1): 380, 2021 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-34496899

RESUMEN

BACKGROUND: Smith-Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder characterized by intellectual disability and severe behavioural and sleep disturbances. Often, patients with SMS are diagnosed with attention-deficit/hyperactivity disorder (ADHD). However, the effectiveness of methylphenidate (MPH), the first-line pharmacological treatment for ADHD, in patients with SMS is unclear. Our objective is to examine the effectiveness of MPH for ADHD symptoms in individuals with SMS, proposing an alternative trial design as traditional randomized controlled trials are complex in these rare and heterogeneous patient populations. METHODS AND ANALYSIS: We will initiate an N-of-1 series of double-blind randomized and placebo-controlled multiple crossover trials in six patients aged ≥ 6 years with a genetically confirmed SMS diagnosis and a multidisciplinary established ADHD diagnosis, according to a power analysis based on a summary measures analysis of the treatment effect. Each N-of-1 trial consists of a baseline period, dose titration phase, three cycles each including randomized intervention, placebo and washout periods, and follow-up. The intervention includes twice daily MPH (doses based on age and body weight). The primary outcome measure will be the subscale hyperactivity/inattention of the Strengths and Difficulties Questionnaire (SDQ), rated daily. Secondary outcome measures are the shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index, Goal Attainment Scaling (GAS), and the personal questionnaire (PQ). Statistical analysis will include a mixed model analysis. All subjects will receive an assessment of their individual treatment effect and data will be aggregated to investigate the effectiveness of MPH for ADHD in SMS at a population level. CONCLUSIONS: This study will provide information on the effectiveness of MPH for ADHD in SMS, incorporating personalized outcome measures. This protocol presents the first properly powered N-of-1 study in a rare genetic neurodevelopmental disorder, providing a much-needed bridge between science and practice to optimize evidence-based and personalized care. TRIAL REGISTRATION: This study is registered in the Netherlands Trial Register (NTR9125).


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Síndrome de Smith-Magenis , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/genética , Estimulantes del Sistema Nervioso Central/uso terapéutico , Método Doble Ciego , Humanos , Metilfenidato/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome de Smith-Magenis/tratamiento farmacológico , Resultado del Tratamiento
10.
Ned Tijdschr Geneeskd ; 161: D2035, 2017.
Artículo en Holandés | MEDLINE | ID: mdl-29171377

RESUMEN

Antipsychotic medication is frequently prescribed for off-label use in individuals with intellectual disability and elderly persons, in particular to reduce challenging behaviour. However, clear evidence for effectiveness is scarce and long-term use of antipsychotics is associated with a wide range of serious side-effects, including movement disorders and metabolic syndrome. Therefore, off-label use of antipsychotics in these populations has been widely debated. Nevertheless, non-pharmacological interventions alone are not always effective and a treatment attempt with an antipsychotic is sometimes inevitable. In this commentary, it is argued that clinicians should focus on the decision-making process in prescribing antipsychotics, rather than focus on discontinuation of these medications.


Asunto(s)
Antipsicóticos/uso terapéutico , Discapacidad Intelectual/tratamiento farmacológico , Uso Fuera de lo Indicado , Humanos
11.
Ned Tijdschr Geneeskd ; 161: D690, 2017.
Artículo en Holandés | MEDLINE | ID: mdl-28198344

RESUMEN

A 72-year-old woman who recently had been treated with metronidazole presented with subacute dysarthria, gait ataxia and encephalopathy with severe anxiety. Head MRI showed symmetrical T2-hyperintensities. Under suspicion of a metronidazole-induced encephalopathy, metronidazole was stopped immediately. The patient recovered completely and follow-up MRI showed complete resolution of T2-hyperintensities.


Asunto(s)
Encefalopatías/inducido químicamente , Metronidazol/efectos adversos , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética
12.
FEBS Lett ; 444(2-3): 155-9, 1999 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-10050749

RESUMEN

Salmon insulin-like growth factor-I (sIGF-I) expression is, as in mammals, induced by growth hormone (GH). To elucidate the mechanism by which GH stimulates the transcription of the IGF-I gene, we transiently transfected Hep3B cells expressing the rat GH receptor with a sIGF-I promoter-luciferase reporter construct. Activation of the construct by GH added to the medium of the transfected cells was observed when two specific transcription factors, STAT5 and HNF-1alpha, were simultaneously overexpressed in these cells. This finding demonstrates for the first time a GH-dependent activation of an IGF-I promoter construct in an immortalized laboratory cell line.


Asunto(s)
Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica/genética , Hormona del Crecimiento/farmacología , Factor I del Crecimiento Similar a la Insulina/genética , Proteínas de la Leche , Proteínas Nucleares , Transactivadores/genética , Factores de Transcripción/genética , Animales , Genes Reporteros/genética , Factor Nuclear 1 del Hepatocito , Factor Nuclear 1-alfa del Hepatocito , Factor Nuclear 1-beta del Hepatocito , Regiones Promotoras Genéticas/genética , Receptores de Somatotropina/genética , Factor de Transcripción STAT5 , Salmón/metabolismo , Activación Transcripcional/genética , Transfección/genética , Células Tumorales Cultivadas
13.
Curr Top Med Chem ; 12(21): 2303-13, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23279171

RESUMEN

22q11.2 Deletion syndrome (22q11DS) is the most common known recurrent copy-number variant disorder. It is also the most common known genetic risk factor for schizophrenia. The greater homogeneity of subjects with schizophrenia in 22q11DS compared with schizophrenia in the wider non-deleted population may help to identify much needed information on neuroanatomical substrates, and neurochemical and neurofunctional mechanisms that may modulate the risk for schizophrenia. Identification of the underlying pathophysiology creates opportunities for developing genotype-specific, biology-based and targeted treatments to prevent, delay or minimize the severity of schizophrenia in both 22q11DS and the wider non-deleted population. This article reviews neuroimaging studies that focused on brain structure and function in this high-risk population, with particular attention to schizophrenia research. We also discuss the evidence on the role of candidate genes within the 22q11.2 region, with particular reference to catechol-O-methyl transferase (COMT) and proline dehydrogenase (PRODH).


Asunto(s)
Síndrome de DiGeorge/fisiopatología , Síndrome de DiGeorge/psicología , Neuroimagen/métodos , Esquizofrenia/genética , Encéfalo/anomalías , Catecol O-Metiltransferasa/genética , Síndrome de DiGeorge/genética , Imagen de Difusión Tensora , Predisposición Genética a la Enfermedad , Ácido Glutámico/análisis , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Imagen Molecular/métodos , Prolina Oxidasa/genética , Esquizofrenia/fisiopatología
14.
J Psychopharmacol ; 24(10): 1525-31, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19406852

RESUMEN

It has been hypothesised that in subjects with 22q11 deletion syndrome (22q11DS) disturbances of the dopamine (DA) system contribute to their increased risk for cognitive deficits and psychiatric problems. However, central DAergic neurotransmission in 22q11DS has not been investigated. We measured striatal D2 receptor binding potential (D2R BP(ND)) using (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide-single photon emission computed tomography ([¹²³I]IBZM SPECT) in 12 adults with 22q11DS and 12 matched controls. Correlations between D2R BP(ND) and plasma prolactin (pPRL) levels were also determined. 22q11DS subjects and controls had similar D2R BP( ND). There was a positive correlation between D2R BP( ND) and pPRL values in controls, but no such relation was found in 22q11DS subjects. This study suggests that a 22q11 deletion does not affect striatal DAergic neurotransmission in the living human brain. However, the disturbed relationship between D2R BP(ND) and pPRL values suggests DAergic dysfunction at a different level. Further studies on DAergic function in extra-striatal brain regions and under challenged conditions are needed.


Asunto(s)
Síndrome de Deleción 22q11/fisiopatología , Benzamidas , Cuerpo Estriado/fisiopatología , Antagonistas de Dopamina , Pirrolidinas , Receptores de Dopamina D2/metabolismo , Transmisión Sináptica , Síndrome de Deleción 22q11/sangre , Síndrome de Deleción 22q11/metabolismo , Adolescente , Adulto , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Cuerpo Estriado/metabolismo , Femenino , Humanos , Radioisótopos de Yodo , Masculino , Especificidad de Órganos , Prolactina/sangre , Índice de Severidad de la Enfermedad , Tomografía Computarizada de Emisión de Fotón Único , Adulto Joven
16.
J Food Prot ; 46(6): 533-536, 1983 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30917479

RESUMEN

Rapid Perfringens Medium (RPM), Perfringens Enrichment Medium (PEM) and Tryptose Sulfite Cycloserine agar medium (TSC) were compared for determination of Clostridium perfringens in spices and herbs. Of 147 samples, 62 (42%) contained C. perfringens when RPM was used; lower percentages of positive isolations were found with PEM (23%), TSC surface plate (19%) and TSC pour plates (26%). Heat-treatment of sample suspensions yielded additional isolates. C. perfringens was isolated by one or more of the techniques from 43 (80%) of 54 different kinds of spices and herbs and from 86 (59%) of 147 samples. Replacing glucose in RPM with raffinose and polymyxin and neomycin with cycloserine did not improve the efficacy of this medium. A good correlation was found between conventional confirmation tests for C. perfringens and tests for acid phosphatase, lecithinase, reverse CAMP test and an antiserum test.

17.
J Autoimmun ; 14(4): 335-41, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10882060

RESUMEN

Nowadays there is compelling evidence for immunoregulation by T cells. Recently, we showed that so-called 'anergic' T cells are not functionally inert but can act as regulatory cells by actively suppressing other T cell responses. We now show that 'anergic' T cells mediate this suppressive effect via modulation of the T-cell activating capacity of the antigen-presenting cell (APC). Upon removal of the 'anergic' T cells, the suppressive APC phenotype persisted, indicating that 'anergic' T cells conditioned the APC to become a mediator of T cell suppression. The inhibitory signal delivered by 'anergic' T cells depended on the presence of the cognate ligand for the 'anergic' T cell, and appeared to be dominant since previously activated APC were rendered inhibitory as well. These findings imply that APC upon cross-talk with T cells can adopt distinct functional phenotypes ranging from T-cell stimulatory to T-cell suppressive. The contribution of 'anergic' T cells to the functional tuning of APC offers an explanation for the maintenance of 'anergic' T cells in the repertoire, and for their role in immunoregulation.


Asunto(s)
Células Presentadoras de Antígenos/inmunología , Linfocitos T CD4-Positivos/inmunología , Anergia Clonal/inmunología , Activación de Linfocitos/inmunología , Animales , Células Presentadoras de Antígenos/citología , Linfocitos T CD4-Positivos/citología , Comunicación Celular/inmunología , Regulación hacia Abajo/inmunología , Epítopos de Linfocito T/inmunología , Masculino , Ratas , Ratas Endogámicas Lew
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