RESUMEN
Research on adherence to combination antiretroviral therapy has up to now focused largely upon problems of definition and measurement, and on the identification of barriers and supports. This paper examines the intersection between taking HAART and building a life with HIV/AIDS. Data consist of 214 qualitative interviews with 52 HIV-positive, active illegal drug users. A interpretive analysis drawing upon stigma and fear of disclosure as analytical constructs was applied to explain working tensions between efforts to develop social relationships on the one hand, and attempts to safeguard health through adherence on the other. The analysis specifies a mechanism through which stigma as a social process results in marginalization and exclusion. The hierarchical organization of multiple stigma is also noted. Loneliness and the desire for relatedness is intensified by drug use. Results suggest that persons with HIV/AIDS will not consistently subordinate other interests to prioritize adherence. Interventions aimed at supporting long-term adherence must address experienced conflicts between 'health' and 'life'.
Asunto(s)
Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Cooperación del Paciente/psicología , Aislamiento Social/psicología , Actividades Cotidianas , Adulto , Quimioterapia Combinada , Femenino , Infecciones por VIH/psicología , Humanos , Masculino , Persona de Mediana Edad , Apoyo Social , Factores Socioeconómicos , Estereotipo , Trastornos Relacionados con Sustancias/psicología , Revelación de la VerdadRESUMEN
Gadd45a is a p53-regulated gene whose protein product, like p53, is involved in maintenance of genome stability. Specifically, deletion of Gadd45a leads to extensive aneuploidy as a consequence of centrosome amplification and subsequent abnormal segregation of chromosomes during mitosis. S-phase checkpoints were investigated in Gadd45a(-/-) cells to determine possible defects contributing to the uncoupling of centrosome duplication and DNA replication. In the presence of hydroxyurea, Gadd45a(-/-) mouse embryo fibroblasts show increased centrosome amplification coupled with loss of a sustained S-phase checkpoint. Gadd45a deletion allows another form of genomic instability, gene amplification, when p21 (Cdkn1a gene product) is deleted also. Gene amplification in Gadd45a(-/-)p21(-/-) cells correlated with loss of both G(1) and S-phase checkpoints. Multiple conditions of nutrient deprivation failed to prevent DNA synthesis in Gadd45a(-/-) cells. Gadd45a is therefore required for proper S-phase control and checkpoints under multiple conditions of nutrient deprivation. It is proposed that loss of S-phase control may account for both the uncoupling of DNA replication and centrosome duplication, and conferring gene amplification proficiency in cells lacking Gadd45a(-/-). This is of particular importance for solid tumors, which may lack sufficient nutrients yet are unable to elicit checkpoints preventing genomic instability under these conditions.
Asunto(s)
Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/fisiología , Genes cdc , Inestabilidad Genómica , Proteínas Nucleares/genética , Proteínas Nucleares/fisiología , Fase S/genética , Aneuploidia , Animales , Ácido Aspártico/análogos & derivados , Ácido Aspártico/farmacología , Línea Celular , Centrosoma/efectos de los fármacos , Centrosoma/fisiología , Segregación Cromosómica , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/fisiología , ADN/biosíntesis , Replicación del ADN , Fase G1/efectos de los fármacos , Fase G1/genética , Fase G1/fisiología , Amplificación de Genes , Eliminación de Gen , Regulación de la Expresión Génica , Genes cdc/efectos de los fármacos , Genes p53 , Hidroxiurea/farmacología , Ratones , Ácido Fosfonoacético/análogos & derivados , Ácido Fosfonoacético/farmacología , Fase S/efectos de los fármacosRESUMEN
1. The mouse somatostatin (SRIF) sst2 receptor exists in two splice variants, sst2(a) and sst2(b), which differ in their intracellular carboxy-termini only. The murine sst2(b) receptor was reported to be less prone to agonist-induced desensitization as compared with the sst2(a) receptor. To determine whether a sst2(b) splice variant with similar functional characteristics exists in the rat, we have isolated a cDNA fragment from rat gastric mucosa encoding a sst2(b) receptor and expressed the full-length protein in CHO-K1 cells for functional characterization. 2. This study provides the first evidence for the occurrence in the rat of the sst2(b) receptor, which has a 15 amino acid carboxy-terminus differing in composition to the 38 amino acid C-terminus of the rat sst2(a) receptor. 3. In CHO-K1 cells expressing rat recombinant sst2(a) or sst2(b) receptors, SRIF caused concentration-dependent increases in extracellular acidification rates (EAR) with pEC50 values of 9.0 and 9.9, respectively. Pre-treatment with pertussis toxin (Ptx) caused a rightward displacement of the SRIF concentration-effect curves with pEC50 values of 8.3 (sst2(a) and 8.4 (sst2(b)). 4. SRIF (3 pM-3 nM) also caused concentration-dependent inhibition of forskolin-stimulated cyclic AMP formation in CHO-sst2(a) cells (pIC50 10.5) and CHO-sst2(b) cells (pIC50 10.4). The degree of inhibition was less with higher concentrations of SRIF resulting in bell-shaped concentration-effect curves. Following pre-treatment with Ptx, the inhibitory effect of SRIF was abolished and SRIF caused only increases in cyclic AMP formation. 5. Both the SRIF-induced increases in EAR and inhibition of cyclic AMP formation were susceptible to agonist-induced desensitization, but this was less apparent following pre-treatment with Ptx. 6. This demonstrates that the operational characteristics of the recombinant rat sst2(a) and sst2(b) receptors are broadly similar. Both isoforms couple to Ptx-sensitive as well as -insensitive G proteins and are equally prone to agonist-induced desensitization.
Asunto(s)
Empalme Alternativo , Mucosa Gástrica/metabolismo , Receptores de Somatostatina/genética , Adenilil Ciclasas/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células CHO , Clonación Molecular , Cricetinae , ADN , Datos de Secuencia Molecular , ARN Mensajero/metabolismo , Ratas , Receptores de Somatostatina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de SecuenciaRESUMEN
1. The aim of this study was to determine the location and functional characteristics of the somatostatin (SRIF) receptor type(s) which mediate inhibition of acid secretion in rat isolated gastric mucosa. 2. Gastrin (1 nM-1 microM), dimaprit (10 microM-300 microM) and isobutyl methylxanthine (IBMX, 1 microM-100 microM) all caused concentration-dependent increases in acid output. Responses to gastrin were almost completely inhibited by ranitidine (10 microM) at a concentration which abolished the secretory response to dimaprit. In contrast, responses to IBMX were not changed by ranitidine suggesting that IBMX acts directly on the parietal cell and not indirectly by releasing histamine from enterochromaffin-like (ECL) cells. 3. SRIF-14 (1 nM-1 microM) had no effect on basal acid output, but inhibited acid output produced by gastrin, dimaprit and IBMX in a concentration-dependent manner with respective EC50 values of 46, 54 and 167 nM. The peptidase inhibitors, amastatin (10 microM) and phosphoramidon (1 microM), had no effect on SRIF-induced inhibition of dimaprit stimulated gastric acid secretion. 4. The inhibitory effect of a range of SRIF analogues on gastrin-, dimaprit- and IBMX-induced acid secretion was also studied. Irrespective of the secretagogue used to increase acid output, the rank order of potencies was similar (BIM-23027 = seglitide = octreotide > SRIF-14 = SRIF-28 > L-362,855). The linear peptide BIM-23056 was devoid of agonist or antagonist activity in concentrations up to 1 microM. 5. The sst2 receptor selective peptides, BIM-23027, seglitide and octreotide were the most potent inhibitors of gastrin-, dimaprit- and IBMX-induced acid secretion suggesting that SRIF receptors resembling the recombinant sst2 receptors are involved. Furthermore, since dimaprit and IBMX stimulate gastric acid secretion independently of histamine release, sst2 receptor-mediated inhibition must occur at the level of the parietal cell itself.
Asunto(s)
Mucosa Gástrica/efectos de los fármacos , Células Parietales Gástricas/efectos de los fármacos , Receptores de Somatostatina/fisiología , 1-Metil-3-Isobutilxantina/farmacología , Animales , Femenino , Mucosa Gástrica/fisiología , Gastrinas/farmacología , Técnicas In Vitro , Oligopéptidos/farmacología , Células Parietales Gástricas/fisiología , Inhibidores de Proteasas/farmacología , Ranitidina/farmacología , Ratas , Ratas Wistar , Receptores de Somatostatina/efectos de los fármacosRESUMEN
The treatment environment is an important component of patient care. In order to provide more effective patient care one would want to be able to manipulate the environment, particularly the emotional environment. This is difficult to do and even more difficult to teach. The authors describe a teaching module in a baccalaureate program in nursing in which didactic sessions and behavioral rehearsal analysis techniques are combined. The goal is to teach interpersonal manipulation for more effective management of professional nursing practice. The results have been promising.