Expanded clinical phenotype of women with the FMR1 premutation.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is generally considered to be uncommon in older female carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene; however, neither prevalence, nor the nature of the clinical phenotype, has been well characterized in female carriers. In this study, we evaluated 146 female carriers (mean, 42.3 years; range, 20-75 years) with and without core features of FXTAS (tremor; gait ataxia), and 69 age-matched controls (mean, 45.8 years; range, 21-78 years). Compared with controls, carriers with definite or probable FXTAS had greater medical co-morbidity, with increased prevalence of thyroid disease (P = 0.0096), hypertension (P = 0.0020), seizures (P = 0.0077), peripheral neuropathy (P = 0.0040), and fibromyalgia (P = 0.0097), in addition to the typical symptoms of FXTAS-tremor (P < 0.0001) and ataxia (P < 0.0001). The non-FXTAS premutation group had more complaints of chronic muscle pain (P = 0.0097), persistent paraesthesias in extremities (P < 0.0001), and history of tremor (P < 0.0123) than controls. The spectrum of clinical involvement in female carriers with FXTAS is quite broad, encompassing a number of medical co-morbidities as well as the core movement disorder. The remarkable degree of thyroid dysfunction (17% in the non-FXTAS group and 50% in the FXTAS group) warrants consideration of thyroid function studies in all female premutation carriers, particularly those with core features of FXTAS.

A novel 165-kDa Golgin protein induced by brain ischemia and phosphorylated by Akt protects against apoptosis.

A cDNA encoding a novel protein was cloned from ischemic rat brain and found to be homologous to testis Mea-2 Golgi-associated protein (Golga3). The sequence predicted a 165-kDa protein, and in vitro translated protein exhibited a molecular mass of 165-170 kDa. Because brain ischemia induced the mRNA, and the protein localized to the Golgi apparatus, this protein was designated Ischemia-Inducible Golgin Protein 165 (IIGP165). In HeLa cells, serum and glucose deprivation-induced caspase-dependent cleavage of the IIGP165 protein, after which the IIGP165 fragments translocated to the nucleus. The C-terminus of IIGP165, which contains a LXXLL motif, appears to function as a transcriptional co-regulator. Akt co-localizes with IIGP165 protein in the Golgi in vivo, and phosphorylates IIGP165 on serine residues 345 and 134. Though transfection of IIGP165 cDNA alone does not protect HeLa cells from serum deprivation or Brefeldin-A-triggered cell death, co-transfection of both Akt and IIGP165 cDNA or combined IIGP165-transfection with PDGF treatment significantly protects HeLa cells better than either treatment alone. These data show that Akt phosphorylation of IIGP165 protects against apoptotic cell death, and add to evidence that the Golgi apparatus also plays a role in regulating apoptosis.

[Clinicopathologic features and treatment of ductal carcinoma in situ of the breast].

OBJECTIVE: To investigate the clinicopathologic features of and appropriate treatment of ductal carcinoma in situ of the breast (DCIS). METHODS: The clinical and pathologic data of 41 cases of DCIS, aged 52.7 (30-82), 15 of which were diagnosed as with ductal carcinoma in situ with microinvasion (DCIS-MI) and of which 18 were in the Van Nuys grade I, 13 in the grade II, and 10 in the grade III, were collected and analyzed. Immunohistochemical analysis was performed to examine the expressions of estrogen receptor (ER), progesterone receptor (PR), proliferating cell nuclear antigen (PCNA), P53 and C-erbB-2. RESULTS: Microinvasion was correlated with the histologic categories (chi(2) = 4.60, P < 0.05) and tumor size (chi(2) = 9.78, P < 0.05) significantly. The expression rates of ER, PR, PCNA, P53, and C-erbB-2 were 68.3%, 65.9%, 63.4%, 26.8%, and 46.3%, respectively. There was no significant difference in the expression of the biologic markers between the patients with DCIS and those with DCIS-MI. The expression levels of ER, P53, and C-erbB-2 were correlated with the histologic categories significantly (chi(2) = 11.45, 11.97, 4.38, P < 0.05). CONCLUSION: The Van Nuys histologic classification accords with the requirement of clinical treatment and prognosis. The patients with DCIS should undergo individualized treatment.

Localization of two homologous Arabidopsis kinesin-related proteins in the phragmoplast.

During plant cytokinesis, kinesin-related motor proteins are believed to play critical roles in microtubule organization and vesicle transport in the phragmoplast. Previously, we reported that the motor AtPAKRP1 was associated with the plus end of phragmoplast microtubules in Arabidopsis thaliana [Lee Y-RJ, Liu B (2000) Curr Biol 10:797-800]. In this paper, we report a full-length cDNA from the same organism, which encodes a polypeptide 74% identical to AtPAKRP1. This AtPAKRP1-like protein--AtPAKRP1L--and AtPAKRP1 share similar domain structures along the polypeptides. Peptide antibodies were raised and purified to distinguish the two polypeptides in vitro and in vivo. When monospecific anti-AtPAKRP1 and anti-AtPAKRP1L antibodies were used in immunofluorescence, they both decorated the plus end of phragmoplast microtubules at all stages of phragmoplast development. Their localization patterns were indistinguishable from each other. By using bacterially expressed fusion proteins of motor-less versions of both polypeptides, it was revealed that AtPAKRP1 and AtPAKRP1L were able to interact with themselves and with each other. Using T-DNA insertional mutants, it was also demonstrated that AtPAKRP1 and AtPAKRP1L were not required for each other's localization. Our results therefore indicate that AtPAKRP1 and AtPAKRP1L are both expressed in the same cells, and likely have identical functions in the phragmoplast by forming either homodimers or heterodimers.