To evaluate diffusion-weighted echo-planar magnetic resonance (MR) imaging for improving the specificity of characterization of liver tumors.
Diffusion-weighted echo-planar imaging was performed with ...a 1.5-T whole-body imager with use of a body phased-array coil in 51 patients with 59 hepatic masses (41 malignant tumors, nine hemangiomas, and nine cysts). Apparent diffusion coefficient (ADC) values were obtained with two motion-probing gradients (b = 30 and 1,200 sec/mm2) during each of the breath-hold periods, and an ADC map was constructed. The T2 was derived from spin-echo echo-planar images with echo times of 47 and 99 msec.
The ADC value of malignant masses (1.04 x 10(-3) mm2/sec) was significantly lower (P < .01) than that of benign masses (hemangiomas 1.95 x 10(-3) mm2/sec and cysts 3.05 x 10(-3) mm2/sec), although the T2s showed considerable overlap. A small amount of overlap in ADC values occurred among malignant tumors, hemangiomas, and cysts. ADC values of two cystic masses from ovarian carcinomas were within the range of those of hemangiomas.
These preliminary results indicate that diffusion-weighted MR imaging can be useful in characterizing focal liver masses. With the exception of cystic metastatic tumors, the technique may be especially useful in tumors that appear markedly hyperintense on T2-weighted images due to a long T2.
Molecular regulation of fibrosis in chronic canine hepatitis is poorly understood. The authors employed quantitative polymerase chain reaction (PCR) to determine the expression levels of genes ...reported to be related to fibrosis in other species (human, mouse, and rat) and to elucidate the relationship of these genes with the degree of fibrosis and the presence or absence of ascites and/or jaundice in dogs with hepatitis. Nine fibrosis-related genes were assayed: PDGFB, PDGFD, MMP2, TIMP1, THBS1, COL1A1, COL3A1, TGFB1, and TGFB2. Liver samples of 15 dogs with chronic hepatitis and 4 healthy control dogs were obtained via laparoscopic biopsy and subjected to histologic and quantitative PCR analyses. The expression of all 9 genes showed significant positive correlation (P < .01, r > .70) with the degree of fibrosis. Furthermore, the expression levels of all genes except TGFB1 were significantly higher (P < .05) in dogs with hepatic failure–related symptoms (ascites/jaundice). Results suggest that these 9 genes are integral to the development of fibrosis in canine chronic hepatitis.
When considering the genetic implications of immigrant gene flow, it is important to evaluate both the proportions of immigrant gametes and their genetic composition. We simultaneously investigated ...paternal and maternal gene flow in dispersed seeds in a natural population of Pinus densiflora located along a ridge. The paternity and maternity of a total of 454 dispersed seeds (in 2004 and 2005) were accurately and separately assigned to 454 candidate adult trees, by analyzing the nuclear DNA of both diploid biparentally derived embryos and haploid maternally derived megagametophytes of the seeds. The relative genetic diversities and differences between within-population and immigrant groups of both paternally and maternally derived gametes (4 groups) that formed the genotypes of the seeds were evaluated. Using 8 microsatellite markers, we found that 64.0-72.6% of paternally derived gametes, and 17.8-20.2% of maternally derived gametes, were from other populations. Principal coordinate analysis showed that the 4 gamete groups tended to be plotted at different locations on the scattergram, indicating that they each have different genetic compositions. Substantial paternal and maternal immigrant gene flow occurred in this population, and therefore, the overall genetic variation of dispersed seeds is enhanced by both paternally and maternally derived immigrant gametes.
The yeast vacuole is functionally and structurally equivalent to the mammalian lysosome. Delivery of resident and cargo proteins to the lysosome is vital for proper cellular operations, and failure ...to correctly target proteins to the organelle is correlated with the development of neurodegenerative and lysosomal storage diseases. We previously reported a novel mutant screen for vacuolar trafficking defects in yeast Saccharomyces cerevisiae that resulted in the isolation of env1, an allelic mutant of VPS35. As a member of the retromer complex, Vps35p binds directly to cargos and facilitates their retrograde transport to trans Golgi from endosomes. Our previous studies established that env1 exhibits unique pleiotropic phenotype in comparison to other tested VPS35 alleles including severe growth sensitivity to hygromycin B and internal accumulation of the precursor form of the vacuolar enzyme carboxypeptidase Y. Here, through a combination of sub-cellular fractionation and indirect immunofluorescence microscopy, we confirm and extend the unique phenotype of env1 to processing and localization of additional proteins within the vacuolar trafficking pathway. In comparative studies with a null and an allelic mutant of VPS35, env1 exhibited unique processing defects of retromer-independent vacuolar membrane enzyme alkaline phosphatase at the vacuole and significant Golgi localization of retromer cargos Vps10p and Kex2p despite compromised trafficking at the Golgi and late endosome interface.
We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related ...macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry UMIN-CTR number, UMIN000011929 .).
Abstract Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant congenital disorder characterized by postnatal progressive heterotopic ossification in soft tissues, especially skeletal ...muscle. In FOP, acute heterotopic ossification is induced by muscle injury, such as accidental trauma or surgical operations. Currently, no definitive treatment exists for FOP. The activin receptor type IA/ activin-like kinase 2 ( ACVR1/ALK2 ) gene has been identified as the responsible gene for both familial and sporadic cases of FOP, and disease-associated ALK2 mutations have been found. ALK2 protein, which is one of the signaling receptors for bone morphogenetic proteins (BMPs) and which induce heterotopic bone formation in skeletal muscle in vivo and initiate the differentiation pathway through which myoblasts convert to osteoblastic cells in vitro . Chemical inhibitors such as dorsomorphin to the pathogenic ALK2 receptors are considered possible medical agents for FOP, but their adverse effects on normal ALK2 and other receptors cannot be excluded. Here we describe another treatment strategy for FOP using allele-specific RNA interference (ASP-RNAi), and show modified small interfering RNAs (siRNAs) conferring allele-specific silencing against disease-causing ALK2 mutants (R206H and G356D) found in FOP, without affecting normal ALK2 allele. Thus, the siRNAs presented here may become novel therapeutic agents for FOP, and their induced ASP-RNAi may pave the way for the achievement of radical treatment of FOP and/or for the relief of its severe symptoms. Takahashi M et al. PNAS 2010;107(50):21731–6; Takahashi M et al. Gene Therapy 2011, in press.
Recently, we identified a novel human virus with a circular DNA genome of 3.2 kb, tentatively designated as torque teno midi virus (TTMDV), with a genomic organization resembling those of torque teno ...virus (TTV) of 3.8-3.9 kb and torque teno mini virus (TTMV) of 2.8-2.9 kb. To investigate the extent of genomic variability of TTMDV genomes, the full-length sequence was determined for 15 TTMDV isolates obtained from viremic individuals in Japan. The 15 TTMDV isolates comprised 3175-3230 bases and shared 67.0-90.3% identities with each other, and were only 68.4-73.0% identical to the 3 reported TTMDV isolates over the entire genome. TTMDV possessed a genomic organization with four open reading frames (ORF1-ORF4) with characteristic sequence motifs and stem and loop structures with high GC content, similar to TTV and TTMV. The total of 18 TTMDV genomes differed by up to 60.7% from each other in the amino acid sequence of ORF1 (658-677 amino acids), but segregated phylogenetically into the same cluster, which was distantly related to the TTVs and TTMVs. These results indicate that TTMDV with a circular DNA genome of 3.2 kb, has an extremely high degree of genomic variability, and is classifiable into a third group in the genus Anellovirus.
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