The two most consistent features of the diseases caused by trinucleotide repeat expansion—neuropsychiatric symptoms and the phenomenon of genetic anticipation—may be present in forms of dementia, ...hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identity and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of ∼3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5′-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87–88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13.
In recent years, several of 99mTc-labeled myocardial perfusion imaging agents have been developed, such as 99mTc-sestamibi, 99mTc-tetrofosmin and 99mTc-furifosmin. Although images obtained with these ...new tracers have a general similar appearance, there are differences in the myocardial kinetics, body distribution, general quality of images and imaging protocols. The aim of this study was to quantitatively compare normal exercise planar and SPECT data files obtained with 201TI and 99mTc-labeled agents.
Lower-limit-of-normal curves were generated for each specific radiopharmaceutical from normal subjects with low (< 3%) pretest likelihood of coronary artery disease using circumferential count distribution profiles from planar and SPECT exercise images. Lower-limit-of-normal curves were statistically compared using the nonparametric Kruskall-Wallis and Wilcoxon tests.
Planar and SPECT lower-limit-of-normal curves generated for each radiopharmaceutical showed general similarities. Statistically significant differences among the lower-limit-of-normal curves were found in the planar left anterior oblique view and in the planar left lateral view (p < 0.05 for each). No statistically significant differences existed between lower-limit-of-normal curves of various radiopharmaceuticals on the planar anterior view and on SPECT imaging.
For quantitative analysis of planar images, radiopharmaceutical-specific normal data files are mandatory. Although SPECT normal data files of various radiopharmaceuticals are not statistically different, they are not identical. It appears, nevertheless, prudent to use radiopharmaceutical-specific normal data files for quantitative analysis of SPECT images.
Recipient antigen presenting cells (APCs) are required for CD8-mediated GVHD and have an important and nonredundant role in CD4-mediated GVHD in mouse MHC-matched allogeneic bone marrow ...transplantation (alloBMT). However, the precise roles of specific recipient APCs — dendritic cells, macrophages, and B cells — are not well defined. If recipient B cells are important APCs they could be depleted with Rituximab, an anti-CD20 monoclonal antibody. On the other hand, B cells can downregulate T cell responses and consequently B cell depletion could exacerbate GVHD. Patients with B cell lymphomas undergo allogeneic hematopoietic stem cell transplantation (alloSCT) and many are B-cell-deficient due to prior Rituximab. We therefore studied the role of recipient B cells in MHC-matched murine models of CD8- and CD4-mediated GVHD by using recipients genetically deficient in B cells and with antibody-mediated depletion of host B cells. In both CD4-and CD8-dependent models, B cell deficient recipients developed clinical and pathologic GVHD. However, although CD8-mediated GVHD was clinically less severe in hosts genetically deficient in B cells, it was unaffected in anti-CD20-treated recipients. These data indicate that recipient B cells are not important initiators of GVHD and that efforts to prevent GVHD by APC depletion should focus on other APC subsets.
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