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Background. A decline in cognitive test scores in elderly persons can signal the beginning of a descent into dementia or may indicate only a short-term cognitive disturbance. It would be clinically useful to distinguish between the two outcomes and to identify characteristics of each. Methods. Four hundred thirty-seven community-dwelling elderly persons were given the Mini-Mental State Examination (MMSE) annually for an average of 7 years. A low score between baseline and final MMSE was identified. A low score 3 or more points lower than baseline score indicated cognitive decline. This decline was called persistent if the final MMSE score was also at least 3 points lower than baseline MMSE score; otherwise, the decline was considered transient. Results. Twenty participants (4.6%) experienced a persistent cognitive decline, 67 participants (15.3%) experienced a transient cognitive decline. Presence of the apolipoprotein [epsilon]4 allele was significantly associated with persistent cognitive decline (age-adjusted odd ratio [OR] = 11.46, p < .0001) but not with transient cognitive decline (age-adjusted OR = 1.53, p = .219). Incorrect answers on the orientation part of the MMSE at the time of cognitive decline was associated with persistent decline compared to transient decline (age-adjusted OR = 3.58, p = .058). Conclusions. Persistent cognitive decline is an infrequent occurrence in community-dwelling elderly persons. Presence of the [epsilon]4 allele and errors made by the subject on questions of orientation may be useful in determining whether a cognitive decline is likely to be persistent.

Research has been conducted on Brca1 full-length isoform. Results demonstrate that Brca1 deficiency triggers pathologic and physiologic responses resulting in premature aging at the organismal level and in p53-dependent, p21-associated senescence at the cellular level.

Background. A decline in cognitive test scores in elderly persons can signal the beginning of a descent into dementia or may indicate only a short-term cognitive disturbance. It would be clinically useful to distinguish between the two outcomes and to identify characteristics of each. Methods. Four hundred thirty-seven community-dwelling elderly persons were given the Mini-Mental State Examination (MMSE) annually for an average of 7 years. A low score between baseline and final MMSE was identified. A low score 3 or more points lower than baseline score indicated cognitive decline. This decline was called persistent if the final MMSE score was also at least 3 points lower than baseline MMSE score; otherwise, the decline was considered transient. Results. Twenty participants (4.6%) experienced a persistent cognitive decline, 67 participants (15.3%) experienced a transient cognitive decline. Presence of the apolipoprotein e4 allele was significantly associated with persistent cognitive decline (age-adjusted odd ratio [OR] = 11.46, p < .0001) but not with transient cognitive decline (age-adjusted OR = 1.53, p = .219). Incorrect answers on the orientation part of the MMSE at the time of cognitive decline was associated with persistent decline compared to transient decline (age-adjusted OR = 3.58, p = .058). Conclusions. Persistent cognitive decline is an infrequent occurrence in community-dwelling elderly persons. Presence of the ε4 allele and errors made by the subject on questions of orientation may be useful in determining whether a cognitive decline is likely to be persistent. [ABSTRACT FROM AUTHOR]

Smad4 is a central mediator for TGFβ signals, which play important functions in many biological processes. To study the role of Smad4 in mammary gland development and neoplasia, we disrupted this gene in mammary epithelium using a Cre-loxP approach. Smad4 is expressed in the mammary gland throughout development; however, its inactivation did not cause abnormal development of the gland during the first three pregnancies. Instead, lack of Smad4 gradually induced cell proliferation, alveolar hyperplasia and transdifferentiation of mammary epithelial cells into squamous epithelial cells. Consequently, all mutant mice developed squamous cell carcinoma and/or mammary abscesses between 5 and 16 months of age. We demonstrated that absence of Smad4 resulted in β-catenin accumulation at onset and throughout the process of transdifferentiation, implicating β-catenin, a key component of the Wnt signaling pathway, in the development of squamous metaplasia in Smad4-null mammary glands. We further demonstrated that TGFβ1 treatment degraded β-catenin and induced epithelialmesenchymal transformation in cultured mammary epithelial cells. However, such actions were blocked in the absence of Smad4. These findings indicate that TGFβ/Smad4 signals play a role in cell fate maintenance during mammary gland development and neoplasia. [ABSTRACT FROM AUTHOR]

Focuses on a study that examined the significance of the interactions between the breast cancer associated gene 1 (BRCA1) and other proteins. Role of the germline mutations of BRCA1 in breast and ovarian cancers; Roles of the BRCA1 tumor suppressor gene in several cellular pathways; Involvement of BRCA1 in DNA-damage repair and centrosome duplication.

Presents a study which showed that the absence of the Brca1 full-length isoform causes senescence in mutant embryos and cultured cells as well as aging and tumorigenesis in adult mice. Link between cell senescence and aging; Nature of senescence; Senescence phenotypes in Brca1 embryos.

Transforming growth factor-beta (TGF-beta) regulates proliferation, morphogenesis, and functional differentiation in the mammary gland and plays complex roles in mammary tumorigenesis. Here we show that the signaling mediators Smad1-Smad5 are expressed at all stages of mammary gland development. To begin to investigate which Smads mediate which TGF-beta responses, we have analyzed mammary gland development in Smad3 null mice. Smad3 null virgin females showed delayed mammary gland development. However, this phenotype was secondary to ovarian insufficiency because Smad3 null mammary epithelium developed normally in hormonally supplemented Smad3 null mice or when transplanted into wild-type hosts. Absence of Smad3 had no effect on the ability of TGF-beta to inhibit the growth of mammary epithelial cells in culture, and no compensatory changes in expression or activation of Smad2 were seen in the Smad3 null epithelium. A small but significant decrease in apoptotic cells was seen in involuting glands from Smad3 null transplants. The results suggest that epithelial Smad3 is dispensable for TGF-beta effects on proliferation and differentiation in the mammary gland, but that it contributes in a nonredundant manner to the induction of apoptosis.