RESUMEN
Using a grounded theory qualitative research, this study explored the strategies used by children to cope with abusive home environments. Through a series of three interviews, a group of adolescents and child care professionals were asked their perceptions regarding protective factors of resilience. These were then categorized into common patterns that emerged as five themes showing a progression of skills used by adolescents who were maltreated as children. These themes are: loyalty to parents, normalizing of the abusive environment, establishing a sense of safety through a perception of invisibility to the abuser, self value, and a future view. This research adds important knowledge to the body of practice skills in working with abusing families. Those children who have developed methods to cope provide us with valuable tools to assist other children who may continue to live in abusing environments.
Asunto(s)
Adaptación Psicológica , Maltrato a los Niños/rehabilitación , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Relaciones Padres-Hijo , Autoimagen , Servicio SocialRESUMEN
Children in the child welfare system face renewed issues of loss as they enter adoptive placements. Every move is a loss and an exercise for the child in establishing the perception of a "safe" environment. Resilient children who have been abused develop coping skills to adapt to their abusing "unsafe" environments. When these children become part of an adoptive family, these coping skills need to be recognized as providing important cues to the child's world, rather than as challenging behaviors. The author deconstructs the words of resilient children into five themes that can help provide access into the children's world, a fresh viewpoint from which to assess the adopted children's reactive behaviors, and a foundation on which an adoptive relationship can be built.
Asunto(s)
Adaptación Psicológica , Maltrato a los Niños/psicología , Relaciones Padres-Hijo , Adolescente , Adopción/psicología , Adulto , Femenino , Cuidados en el Hogar de Adopción , Humanos , MasculinoRESUMEN
Arthroscopic synovectomy was performed on 29 metacarpophalangeal joints belonging to 21 patients with refractory rheumatoid arthritis. This article describes the method of anesthesia, landmarks, and operative technique. Short-term (12-month) results and patient satisfaction have been excellent. No complications were noted. We conclude that arthroscopic synovectomy of the metacarpophalangeal joints in patients with refractory rheumatoid arthritis can be performed safely and effectively. Possibilities for improvement of the technique as well as possible uses of the technique in research are discussed.
Asunto(s)
Artritis Reumatoide/cirugía , Artroscopía , Endoscopía/métodos , Articulación Metacarpofalángica/cirugía , Sinovectomía , Estudios de Seguimiento , Humanos , Resultado del TratamientoRESUMEN
Maturing B lymphocytes possess a recombination activity that switches the class of heavy chain Ig. The nature of the recombination activity, its molecular requirements and regulation remain elusive questions about B lymphocyte biology and development. Class switch recombination is controlled by cytokine response elements that are required to differentially activate CH gene transcription before their subsequent recombination. Here, we show that cultures of purified murine and human B cells, stimulated only by CD40 receptor engagement, possess a potent switch recombination activity. CD40 ligand-stimulated murine and human B lymphocytes were infected with recombinant retroviruses containing Smu and S gamma 2b sequences. Chromosomally integrated switch substrate retrovectors (SSRs), harboring constitutively transcribed S sequences, underwent extensive recombinations restricted to their S sequences with structural features akin to endogenous switching. SSR recombination commenced 4 days postinfection (5 days poststimulation) with extensive switch sequence recombination over the next 2 to 3 days. In contrast, endogenous S gamma 2b and S gamma 1 sequences did not undergo appreciable switch recombination upon CD40 signaling alone. As expected, IL-4 induced endogenous Smu to S gamma 1 switching, while endogenous Smu to S gamma 2b fusions remained undetectable. Surprisingly, IL-4 enhanced the onset of SSR recombination in CD40-stimulated murine B cells, with S-S products appearing only 2 days postinfection and reaching a maximum within 2 to 3 days. The efficiency of switch recombination with SSRs resembles that seen for endogenous C(H) class switching.
Asunto(s)
Antígenos CD40/inmunología , Reordenamiento Génico de Cadena Pesada de Linfocito B , Vectores Genéticos/inmunología , Cambio de Clase de Inmunoglobulina/genética , Regiones Constantes de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/genética , Activación de Linfocitos/genética , Retroviridae/genética , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Linfocitos B/metabolismo , Secuencia de Bases , Antígenos CD40/metabolismo , Reordenamiento Génico de Cadena Pesada de Linfocito B/efectos de los fármacos , Humanos , Cambio de Clase de Inmunoglobulina/efectos de los fármacos , Cadenas gamma de Inmunoglobulina/genética , Cadenas mu de Inmunoglobulina/genética , Interleucina-4/farmacología , Interfase/genética , Interfase/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos DBA , Tonsila Palatina/inmunología , Tonsila Palatina/metabolismo , Transducción de Señal/genética , Transducción de Señal/inmunología , Especificidad por Sustrato/genéticaRESUMEN
Ig heavy chain isotype switching in B lymphocytes is known to be preceded by transcription of a portion of the particular heavy chain gene segment that is targeted for recombination. Here, we describe an active role for these transcripts in the switch recombination process. Using an in vitro assay that exposes an artificial switch-mu (Smu) minisubstrate to switch region transcripts in the presence of nuclear extracts from switching cells, we demonstrate that free 3' ends of the Smu sequence are extended onto switch region transcripts by reverse transcription. The activity was induced in splenic B lymphocytes upon activation with LPS or CD40 ligand. This in vitro process is thought to be relevant to in vivo class switching for two reasons: 1) although only one-third of the Smu minisubstrate actually contains Smu sequence, all crossovers between switch regions occurred in the Smu portion; and 2) treatment of B lymphocytes with IL-4, which enriches for switching to S gamma 1, increases the ratio of Smu-S gamma 1 to Smu-S gamma 3 hybrids by 16% after LPS treatment and by 37% after CD40 ligand activation, implicating this S mu-primed reverse transcription of switch region transcripts as a novel mechanism of regulating the specificity of isotype switching. Further evidence for an active role of switch region transcripts was obtained by expressing S alpha RNA in trans in the Bcl1B1 B lymphoma line. Endogenous S mu-S alpha switch circles were detected in Bcl1B1 cells expressing exogenous S alpha RNA but not in mock-transfected cells.
Asunto(s)
Linfocitos B/metabolismo , ADN/genética , Reordenamiento Génico de Cadena Pesada de Linfocito B , Cadenas Pesadas de Inmunoglobulina/genética , Región de Cambio de la Inmunoglobulina/genética , Cadenas mu de Inmunoglobulina/genética , Animales , ADN/síntesis química , Genes Sintéticos , Cambio de Clase de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/biosíntesis , Isotipos de Inmunoglobulinas/genética , Cadenas mu de Inmunoglobulina/biosíntesis , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos DBA , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes de Fusión/genética , Análisis de Secuencia de ADN , Transcripción Genética/inmunologíaRESUMEN
Chromosomally integrated retroviral switch (S) substrates have been developed to reveal switch recombinase-like activities (SRLA) in pre-B and mature B cell lines. Switch substrate retrovectors (SSR) contain a long-terminal repeat-driven neomycin (Neo) gene for proviral chromosomal maintenance (pre- and post-S recombination) and a CMV promoter-driven, chimeric hygromycin-thymidine kinase (Hytk) gene (flanked by S mu and S gamma 2b recombination targets) to select for (ganciclovir) and against (hygromycin B) S region recombination. The retro-substrates' strong, constitutive promoters ensure that variations in cellular switch recombinase activities are independent of S region accessibility control. By initially selecting for proviral integrants in hygromycin followed by shifting into neomycin + ganciclovir to select for S sequence-mediated deletions, switch recombinations can be specifically forestalled in B cell lines whilst most switch-incompetent cells do not survive secondary selection. A qualitative, direct PCR assay reveals that SSR recombinations are stochastic in B cell lines generating a product array akin to natural GH class switching. A semi-quantitative DC-PCR assay detects a significant recombinase activity only in a restricted set of late stage pre-B and mature B cell lines. BCL1B1 mature B cells have the highest level of recombinase activity with 25% or more of proviral integrants accumulating S mu/S gamma 2b substrate recombinations within 10-14 cell generations. The SSR recombinase assay can be performed in a transient fashion wherein extensive, B cell-specific recombination can be visualized within only a few cell divisions post proviral integration. We propose that switch recombinase activity becomes activated during B cell ontogeny independent of or prior to the acquisition of CH locus accessibility and that endogenous S segment targeting to pre-existing recombinase requires a level of accessibility beyond transcriptional activation.
Asunto(s)
Subgrupos de Linfocitos B/enzimología , ADN Nucleotidiltransferasas/metabolismo , Cambio de Clase de Inmunoglobulina/genética , Células 3T3 , Animales , Subgrupos de Linfocitos B/citología , Subgrupos de Linfocitos B/virología , Diferenciación Celular/inmunología , Regulación Enzimológica de la Expresión Génica/inmunología , Reordenamiento Génico de Cadena Pesada de Linfocito B/genética , Vectores Genéticos/genética , Células HeLa , Humanos , Higromicina B/farmacología , Regiones Constantes de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/genética , Ratones , Neomicina/farmacología , Reacción en Cadena de la Polimerasa , Recombinación Genética , Retroviridae/genética , Sensibilidad y Especificidad , Procesos Estocásticos , Especificidad por Sustrato/genética , Especificidad por Sustrato/inmunología , Timidina Quinasa/metabolismo , VDJ RecombinasasRESUMEN
FET cells are well differentiated human adenocarcinoma cells whose growth is partially inhibited (50-60%) by transforming growth factor-beta 1 (TGF-beta 1). In exponentially growing cultures, TGF-beta 1 induces the expression of transforming growth factor-alpha (TGF-alpha) by 3-fold. To determine whether this induction is the result of increased TGF-alpha promoter activity, FET cells were transiently transfected with a plasmid containing 2816 base pairs of the 5'-flanking region of the TGF-alpha gene linked to luciferase. Transfected FET cells treated with growth-inhibitory concentrations of TGF-beta 1 (10 ng/ml) showed up to a 10-fold increase in luciferase activity. The increase in luciferase activity was dose dependent through the normal physiological range of TGF-beta 1 (0.5-20 ng/ml), saturating at 10 ng/ml. This effect was also TGF-alpha promoter specific, inasmuch as the Rous sarcoma virus long terminal repeat used as a control remained relatively insensitive to the effects of TGF-beta 1. By using progressively smaller portions of the TGF-alpha promoter region, the TGF-beta 1-responsive element was mapped between base pairs -77 and -201 of the 5'-flanking region. TGF-beta 1 treatment also affected epidermal growth factor receptor levels. FET cells treated with TGF-beta 1 (10 ng/ml) for 48 h showed a 20% decrease in the number of epidermal growth factor receptors and a 2-fold increase in the number of high affinity epidermal growth factor receptors on their surface. These results indicate that TGF-beta 1 acts as a positive regulator of TGF-alpha transcription, and they suggest a possible mechanism by which these cells circumvent the growth-inhibitory effects of TGF-beta 1.