No significant benefit with shoulder strapping was demonstrated and reasons for this are discussed. Range of movement in the hemiplegic shoulder is lost very early and any preventive treatments need to begin within the first 1-2 days after a stroke.
The potent growth-promoting activity of insulin-like growth factor-II (IGF-II) is highly regulated during development but frequently up-regulated in tumors. Increased expression of the normally monoallelic (paternally expressed) mouse (Igf2) and human (IGF2) genes modify progression of intestinal adenoma in the Apc Min/+ mouse and correlate with a high relative risk of human colorectal cancer susceptibility, respectively. We examined the functional consequence of Igf2 allelic dosage (null, monoallelic, and biallelic) on intestinal adenoma development in the Apc Min/+ by breeding with mice with either disruption of Igf2 paternal allele or H19 maternal allele and used these models to evaluate an IGF-II-specific therapeutic intervention. Increased allelic Igf2 expression led to elongation of intestinal crypts, increased adenoma growth independent of systemic growth, and increased adenoma nuclear B-catenin staining. By introducing a transgene expressing a soluble form of the full-length IGF-II/mannose 6-phosphate receptor (sIGF2R) in the intestine, which acts as a specific inhibitor of IGF-II ligand bioavailability (ligand trap), we show rescue of the Igf2-dependent intestinal and adenoma phenotype. This evidence shows the functional potency of allelic dosage of an epigenetically regulated gene in cancer and supports the application of an IGF-II ligand-specific therapeutic intervention in colorectal cancer. (Cancer Res 2006; 66(4): 1940-8)
The environmental fate of nitroguanidine (NQ) in surface waters is dominated by photolysis with surface half‐lives at 40°N ranging from 0.6 d in summer to 2.3 d in winter. The environmental quantum yield is 0.01. The NQ is initially photolyzed to nitrite and hydroxyguanidine; nitrite is photochemically converted to nitrate and hydroxyguanidine undergoes sensitized photolysis to unknown products. The photooxidation of nitrite is assisted by organic material in a process not involving H2O2 or singlet oxygen. Nitroguanidine biotransforms cometabolically; in the absence of extra organic nutrients the second‐order rate constant was (3.8 ± 0.9) × 10−10 ml cell−1 h−1. Half‐life estimates for aerobic, aquatic biotransformation range from 1 to 100 d. Cyanamide appears to be an end product of NQ use and no intermediate biotransformation products were observed. Nitroguanidine is expected to move readily through soils (soil sorption coefficient Kp < 0.1); however, anaerobic biotransformation occurs readily in soil, with an estimated half‐life of 4 d.
Other fate parameters measured at 25°C are a water solubility of 2,600 ± 100 ppm, octanol/water partition coefficient of 0.148 ± 0.001 (dimensionless), Henry's constant of < 7 × 10−6 (dimension‐less), base hydrolysis constant of (3 ± 1) × 10−4 M−1 S−1, neutral hydrolysis constant ≤ 2 × 10−8 s−1, and biouptake constants of 110 g dry cells/g water for Anabena flos‐aquae and 150 g dry cells/g water for Selenastrum capricornutum.
The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor that is vital during development of several organs including metanephric kidneys. Despite the critical regulatory role of WT1, the pathways and mechanisms by which WT1 orchestrates development remain elusive. To identify WT1 target genes, we performed a genomewide expression profiling analysis in cells expressing inducible WT1. We identified a number of direct WT1 target genes, including the epidermal growth factor (EGF)-family ligands epiregulin and HB-EGF, the chemokine CX3CL1, and the transcription factors SLUG and JUNB. The target genes were validated using quantitative reverse transcriptase-polymerase chain reaction, small interfering RNA knockdowns, chromatin immunoprecipitation, and luciferase reporter analyses. Immunohistochemistry of fetal kidneys confirmed that a number of the WT1 target genes had overlapping expression patterns with the highly restricted spatiotemporal expression of WT1. Finally, using an in vitro embryonic kidney culture assay, we found that the addition of recombinant epiregulin, amphiregulin, CX3CL1, and interleukin-11 significantly enhanced ureteric bud branching morphogenesis. Our genome-wide screen implicates WT1 in the transcriptional regulation of the EGF-family of growth factors as well as the CX3CL1 chemokine during nephrogenesis.
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