The heterodimeric tumor-suppressor complex BRCA1/BARD1 exhibits E3 ubiquitin ligase activity and participates in cell proliferation and chromosome stability control by incompletely defined mechanisms. Here we show that, in both mammalian cells and Xenopus egg extracts, BRCA1/BARD1 is required for mitotic spindle-pole assembly and for accumulation of TPX2, a major spindle organizer and Ran target, on spindle poles. This function is centrosome independent, operates downstream of Ran GTPase, and depends upon BRCA1/BARD1 E3 ubiquitin ligase activity. Xenopus BRCA1/BARD1 forms endogenous complexes with three spindle-pole proteins, TPX2, NuMA, and XRHAMM--a known TPX2 partner--and specifically attenuates XRHAMM function. These observations reveal a previously unrecognized function of BRCA1/BARD1 in mitotic spindle assembly that likely contributes to its role in chromosome stability control and tumor suppression.
Aim: The trajectory in psychotic disorders which leads from a relatively normal premorbid state in young people to a first episode of psychosis is only partly understood. Qualitative research methods can be used to begin to elucidate the temporal unfolding of symptoms leading to a first episode of psychosis, and its impact on families. Methods:We conducted open-ended interviews with family members of 13 patients with recent onset nonaffective psychotic disorders, which focused on changes observed, effects on the family, explanatory models, help-seeking patterns and future expectations. Standard data analytic methods employed for qualitative research were used. Results:Narratives by family members were remarkably similar. First, social withdrawal and mood symptoms developed in previously normal children; these changes were typically ascribed to drugs or stress, or to the 'storminess' of adolescence. Coping strategies by family members included prayer and reasoning/ persuasion with the young person, and family initially sought help from friends and religious leaders. Entry into the mental health system was then catalysed by the emergence of overt symptoms, such as 'hearing voices', or violent or bizarre behaviour. Family members perceived inpatient hospitalization as traumatic or difficult, and had diminished expectations for the future. Conclusions:Understanding families' explanatory models for symptoms and behavioural changes, and their related patterns of help-seeking, may be useful for understanding evolution of psychosis and for the design of early intervention programmes. Dissatisfaction with hospitalization supports the mandate to improve systems of care for recent-onset psychosis patients, including destigmatization and a focus on recovery.
Objective Qualitative research methods were used to understand the experiences of families seeking treatment for young people with recent-onset psychosis; such knowledge can inform services design. Methods The authors conducted open-ended interviews in 1999 through 2002 with family members of 13 patients with recent-onset nonaffective psychotic disorders in the New York metropolitan area, focusing on their experience in seeking treatment and engaging with mental health services. Results Family members described early lack of clarity of diagnosis and obstacles to obtaining treatment. Entry into the mental health system frequently occurred in the context of crisis, with African-American families specifically reporting police involvement. Inpatient hospitalization was depicted as traumatic yet offering relief. Aftercare was described as fragmented, and issues with third-party payers were paramount. Families expressed a desire for more education, information, and support and described their struggles with stigma. These data from families are presented in the context of more recent literature as to the efficacy of specialized treatment programs for early stages of psychotic disorder and their involvement of families. Conclusions These qualitative research data support the importance of involving and educating families about psychosis: its recognition, its treatment, and access to services. They also highlight the need to address stigma and implement structural changes in treatment that ensure continuity and coverage of care. Specialized first-episode psychosis services may address these issues, and they may minimize the traumatic experiences of involuntary hospitalization and police involvement early in treatment.
Objective Qualitative research methods were used to understand the experiences of families seeking treatment for young people with recent-onset psychosis; such knowledge can inform services design. Methods The authors conducted open-ended interviews in 1999 through 2002 with family members of 13 patients with recent-onset nonaffective psychotic disorders in the New York metropolitan area, focusing on their experience in seeking treatment and engaging with mental health services. Results Family members described early lack of clarity of diagnosis and obstacles to obtaining treatment. Entry into the mental health system frequently occurred in the context of crisis, with African-American families specifically reporting police involvement. Inpatient hospitalization was depicted as traumatic yet offering relief. Aftercare was described as fragmented, and issues with third-party payers were paramount. Families expressed a desire for more education, information, and support and described their struggles with stigma. These data from families are presented in the context of more recent literature as to the efficacy of specialized treatment programs for early stages of psychotic disorder and their involvement of families. Conclusions These qualitative research data support the importance of involving and educating families about psychosis: its recognition, its treatment, and access to services. They also highlight the need to address stigma and implement structural changes in treatment that ensure continuity and coverage of care. Specialized first-episode psychosis services may address these issues, and they may minimize the traumatic experiences of involuntary hospitalization and police involvement early in treatment.
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