Low blood levels of folate and vitamin B12, and elevated tHcy levels were associated with AD. The stability of tHcy levels over time and lack of relationship with duration of symptoms argue against these findings being a consequence of disease and warrant further studies to assess the clinical relevance of these associations for AD.
Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrPC). Here we develop a unique cell system in which epitope-tagged PrPC is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrPC, when expressed in our PrP-KD cells, supports prion replication with the production of bona fide epitope-tagged infectious misfolded PrP (PrPSc). Using this epitope-tagged PrPSc, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.
To characterize prognostic values of androgen receptor (AR) in triple-negative (TN) breast cancers, we investigated AR expression status and levels, explored an association of AR expression with metastatic disease, and correlated AR expression with Ki-67 in TN invasive breast carcinomas. AR expression was analyzed with immunohistochemistry in 121 cases of TN tumors. Thirty-nine cases had distant metastatic disease and 82 had locoregional disease only. AR was positive in 38 (31.4%) of the 121 cases. Our results indicate that among the AR-positive TN tumors, distant metastases are significantly associated with lower expression of AR compared with cases with only locoregional disease, and that AR expression negatively correlates with Ki-67 expression. These findings suggest that decreased intratumoral AR expression may be predictive of distant metastatic disease and AR expression levels may have potential prognostic value in AR-expressing TN tumors.
Triple-negative (TN) breast carcinoma, characterized by estrogen receptor, progesterone receptor, and HER2 negativity, is a group of aggressive tumors that can be further classified into 2 subtypes: basal-like, defined as CK5/6 and/or epidermal growth factor receptor (EGFR) positive by immunohistochemistry; and non-basal-like. Clinical characteristics and tumor profiles were analyzed in 105 cases of TN tumors. Among these cases, 35 had distant metastasis, 34 had axillary nodal metastasis only, and 36 were nodal negative. Our results indicate basal-like TN breast tumors with nodal and distant metastases are significantly associated with a higher intratumoral expression of EGFR and CK5/6 compared to those in the nodal negative group. High level of intratumoral EGFR and CK5/6 expression may play a role in development of nodal or distant metastases in patients with basal-like TN tumors and may be predictive of metastatic disease. Furthermore, EGFR targeted therapy may be potentially useful in the treatment of basal-like TN breast cancer.
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