Background The recently proposed Movement Disorder Society (MDS) Task Force diagnostic criteria for mild cognitive impairment in Parkinson’s disease (PD-MCI) represent a first step towards a uniform definition of PD-MCI across multiple clinical and research settings. Several questions regarding specific criteria, however, remain unanswered including optimal cutoff scores by which to define impairment on neuropsychological tests. Methods Seventy-six non-demented PD patients underwent comprehensive neuropsychological assessment and were classified as PD-MCI or PD with normal cognition (PD-NC). Concordance of PD-MCI diagnosis by MDS Task Force Level II criteria (comprehensive assessment), using a range of standard deviation (SD) cutoff scores, was compared to our consensus diagnosis of PD-MCI or PD-NC. Sensitivity, specificity, positive and negative predictive values were examined for each cutoff score. PD-MCI subtype classification and distribution of cognitive domains impaired were evaluated. Results Concordance for PD-MCI diagnosis was greatest for defining impairment on neuropsychological tests using a 2 SD cutoff score below appropriate norms. This cutoff also provided the best discriminatory properties for separating PD-MCI from PD-NC, compared to other cutoff scores. With the MDS PD-MCI criteria, multiple domain impairment was more frequent than single domain impairment, with predominant executive function, memory, and visuospatial function deficits. Conclusions Application of the MDS Task Force PD-MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at a 2 SD cutoff score. The predominance of multiple domain impairment in PD-MCI with the Level II criteria suggests not only influences of testing abnormality requirements, but also the widespread nature of cognitive deficits within PD-MCI.
We have cloned and characterized a putative protein serine/threonine kinase termed prk through a combination of polymerase chain reaction and conventional cDNA library screening approaches. There are apparently two distinct domains within prk protein deduced from its nucleotide sequences. The amino-terminal portion has the feature of the catalytic domain of a serine/ threonine kinase and shows strong homology to mouse fnk and other polo family kinases including mouse snk, human and murine plk, Drosophila polo, and yeast Cdc5. The carboxyl-terminal portion, presumably the regulatory domain, shares extensive homology to mouse fnk. Northern blotting analyses reveal that prk expression is restricted to a very limited number of tissues with placenta, ovaries, and lung containing detectable amounts of prk mRNA. prk mRNA expression is also detected at a low level in the megakaryocytic cell line Dami, MO7e, and three brain glioma cell lines. In addition, refeeding of serum-deprived MO7e, Dami, and K562 cells of hematopoietic origin and GMOO637D of lung fibroblasts rapidly activates prk mRNA expression with its peak induction around 2 h after serum addition. prk gene activation by the serum requires no new protein synthesis. The recombinant cytokines such as interleukin-3 and thrombopoietin also activate prk mRNA expression in MO7e cells. Furthermore, a survey of RNAs isolated from the tumor and the uninvolved tissues from 18 lung cancer patients reveals that prk mRNA expression is significantly down-regulated in tumor tissues. Southern blotting analysis indicates that the prk gene is present in a single copy in the genome of tumors and normal cells. Taken together, these results suggest that prk expression may be restricted to proliferating cells and involved in the regulation of cell cycle progression. The molecular cloning of prk cDNA will facilitate the study of its biological role as well as its potential role in tumorigenesis.The regulation of eukaryotic cell division, in response to external signals, requires numerous protein kinases. Cyclindependent kinases are a family of protein serine-threonine (Ser/Thr) kinases, and their activities play an essential role in normal cell cycle progression and neoplastic transformation (1, 2). Conversely, activation of chk-1-encoded protein Ser/Thr kinase is associated with cell arrest when the cells are exposed to DNA damage agents (3).The polo (derived from Drosophila polo gene) family protein Ser/Thr kinases (such as mouse fnk and snk, human and mouse plk, Drosophila polo, and yeast cdc5) have been implicated in cell division (4 -11), although their precise mode of action remains unclear. snk encodes a serum-inducible enzyme involved in the early mitogenic response, and its activity is transcriptionally and post-transcriptionally regulated (4). The polo gene encodes a protein Ser/Thr kinase, mutations that result in abnormal mitotic and meiotic division in the fruit fly (5). A polo homolog encoded by cdc5 in budding yeast is required for nuclear division late in the mitotic ...
Our results support the hypotheses that high total intakes of vitamins B-6 and B-12 are protective of depressive symptoms over time in community-residing older adults.
High salinity is one of the most serious threats to crop production. To understand the molecular basis of plant responses to salt stress better, suppression subtractive hybridization (SSH) and microarray approaches were combined to identify the potential important or novel genes involved in the early stage of tomato responses to severe salt stress. First, SSH libraries were constructed for the root tissue of two cultivated tomato (Solanum lycopersicum) genotypes: LA2711, a salt-tolerant cultivar, and ZS-5, a salt-sensitive cultivar, to compare salt treatment and non-treatment plants. Then a subset of clones from these SSH libraries were used to construct a tomato cDNA array and microarray analysis was carried out to verify the expression changes of this set of clones upon a high concentration of salt treatment at various time points compared to the corresponding non-treatment controls. A total of 201 non-redundant genes that were differentially expressed upon 30 min of severe salt stress either in LA2711 or ZS-5 were identified from microarray analysis; most of these genes have not previously been reported to be associated with salt stress. The diversity of the putative functions of these genes indicated that salt stress resulted in a complex response in tomato plants.
Human prk encodes a novel protein serine/threonine kinase capable of strongly phosphorylating casein but not histone H1 in vitro. prk expression is tightly regulated at various levels during different stages of the cell cycle in lung fibroblasts. The Prk kinase activity is relatively low during mitosis, G1, and G1/S, and peaks during late S and G2 stages of the cell cycle. Recombinant human Prk expressed through the baculoviral vector system is capable of phosphorylating Cdc25C, a positive regulator for the G2/M transition. Human prk shares significant sequence homology with Saccharomyces cerevisiae CDC5 and Drosophila melanogaster polo, both of which are essential for mitosis and meiosis. Full-length prk transcripts greatly potentiate progesterone-induced meiotic maturation of Xenopus laevis oocytes. On the other hand, antisense prk transcripts significantly delay and reduce the rate of oocyte maturation. When expressed in a CDC5 mutant strain of S. cerevisiae, human Prk, but not a deletional mutant protein, fully rescues the temperature-sensitive phenotype of the budding yeast. Taken together, prk may represent a new protein kinase, playing an important role in regulating the onset and/or progression of mitosis in mammalian cells.
Background and Purpose-We aimed to determine the prevalence of acute brain infarcts using diffusion-weighted imaging (DWI) in patients with spontaneous intracerebral hemorrhage (ICH
Background The optimal properties of a comprehensive (Level II) neuropsychological battery for determining Parkinson’s disease mild cognitive impairment (PD-MCI) by Movement Disorder Society (MDS) Task Force criteria remain unresolved. Methods Seventy-six non-demented PD patients underwent PD-MCI classification using a consensus diagnosis and Level II criteria. We examined the optimal number of tests in each of the five designated cognitive domains, identified the best tests within each domain, and determined the best overall battery for PD-MCI Level II diagnosis. Results A battery with two tests per domain provided a highly practical, robust diagnostic assessment. Level II testing with the two best tests and impairment defined as 2 standard deviations below norms was highly sensitive and specific for PD-MCI diagnosis. Conclusions Our findings strongly support the MDS Task Force Level II testing recommendations, provide a framework for creating an optimal, efficient neuropsychological test battery for PD-MCI diagnosis, and offer specific test recommendations.
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