Spreading of Antarctic Bottom Water examined using the CFC-11 distribution simulated by an eddy-resolving OGCM

We have investigated the spreading and pathway of Antarctic Bottom Water(AABW) using the simulated distribution of chlorofluorocarbons(CFCs) in a global eddy-resolving(1/10°) OGCM. Our goal is understanding of the processes and pathways determining the distribution of CFCs in the Southern Ocean, where much of this tracer is entrained by formation of deep and bottom water. The simu- lated high CFC-11 water reveals the newly formed AABW around the Antarctic Continent. The main source regions of AABW in the model are in the Weddell Sea(60°- 30°W ), offshore of Wilkes Land(120°- 160°E ) and in the Ross Sea(170°E -160°W ). In our model, spreading of simulated CFC-11 in the deep Southern Ocean from the newly formed AABW regions is more similar to the observed distribution than in coarse-resolution models. In the Weddell Sea, the high CFC-11 water spreads eastward with the Antarctic Circumpolar Current(ACC) and flows northward to the Argentine Basin. The high CFC-11 water from Wilkes Land joins with the high CFC-11 water from the Ross Sea. Some of the high CFC-11 water from Wilkes Land flows northward toward New Zealand. The high CFC-11 water from the Ross Sea flows eastward with the ACC along the Mid Ocean Ridge and northward to the Southeast Pacific Basin

Cationized gelatin-HVJ envelope with sodium borocaptate improved the BNCT efficacy for liver tumors in vivo

<p>Abstract</p> <p>Background</p> <p>Boron neutron capture therapy (BNCT) is a cell-selective radiation therapy that uses the alpha particles and lithium nuclei produced by the boron neutron capture reaction. BNCT is a relatively safe tool for treating multiple or diffuse malignant tumors with little injury to normal tissue. The success or failure of BNCT depends upon the ¹⁰B compound accumulation within tumor cells and the proximity of the tumor cells to the body surface. To extend the therapeutic use of BNCT from surface tumors to visceral tumors will require ¹⁰B compounds that accumulate strongly in tumor cells without significant accumulation in normal cells, and an appropriate delivery method for deeper tissues.</p> <p>Hemagglutinating Virus of Japan Envelope (HVJ-E) is used as a vehicle for gene delivery because of its high ability to fuse with cells. However, its strong hemagglutination activity makes HVJ-E unsuitable for systemic administration.</p> <p>In this study, we developed a novel vector for ¹⁰B (sodium borocaptate: BSH) delivery using HVJ-E and cationized gelatin for treating multiple liver tumors with BNCT without severe adverse events.</p> <p>Methods</p> <p>We developed cationized gelatin conjugate HVJ-E combined with BSH (CG-HVJ-E-BSH), and evaluated its characteristics (toxicity, affinity for tumor cells, accumulation and retention in tumor cells, boron-carrying capacity to multiple liver tumors <it>in vivo</it>, and bio-distribution) and effectiveness in BNCT therapy in a murine model of multiple liver tumors.</p> <p>Results</p> <p>CG-HVJ-E reduced hemagglutination activity by half and was significantly less toxic in mice than HVJ-E. Higher ¹⁰B concentrations in murine osteosarcoma cells (LM8G5) were achieved with CG-HVJ-E-BSH than with BSH. When administered into mice bearing multiple LM8G5 liver tumors, the tumor/normal liver ratios of CG-HVJ-E-BSH were significantly higher than those of BSH for the first 48 hours (<it>p < 0.05</it>). In suppressing the spread of tumor cells in mice, BNCT treatment was as effective with CG-HVJ-E-BSH as with BSH containing a 35-fold higher ¹⁰B dose. Furthermore, CG-HVJ-E-BSH significantly increased the survival time of tumor-bearing mice compared to BSH at a comparable dosage of ¹⁰B.</p> <p>Conclusion</p> <p>CG-HVJ-E-BSH is a promising strategy for the BNCT treatment of visceral tumors without severe adverse events to surrounding normal tissues.</p

Gene expression profiles of circulating leukocytes correlate with renal disease activity in IgA nephropathy

BACKGROUND: The goal of these studies was to explore the possibility of using gene expression profiles of circulating leukocytes as a functional fingerprint of nephritic disease activity. METHODS: This feasibility study utilized IgA nephropathy (IgAN) as a model system. Genes differentially expressed in IgAN patients were identified by Affymetrix GeneChip microarrays, and compared with gene expression of focal segmental glomerulosclerosis (FSGS), minimal change disease, antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis, and with healthy volunteers. Of the genes identified, 15 transcriptionally up-regulated were validated in a larger cohort of patients using TaqMan polymerase chain reaction (PCR). To test whether increased expression of these genes correlated with disease activity, cluster analyses were performed utilizing the TaqMan PCR values. Taking a mathematical approach, we tested whether gene expression values were correlative with kidney function, as reflected by serum creatinine and creatinine clearance values. RESULTS: We identified 15 genes significantly correlative with disease activity in IgAN. This gene signature of IgAN patients' leukocytes reflected kidney function. This was demonstrated in that mathematically generated theoretical values of serum creatinine and creatinine clearance correlated significantly with actual IgAN patient values of serum creatinine and creatinine clearance. There was no apparent correlation with hematuria and proteinuria. The expression levels of this same gene set in ANCA glomerulonephritis or Lupus nephritis patients were not correlative with serum creatinine or creatinine clearance values. CONCLUSION: These data indicate that leukocytes carry informative disease-specific markers of pathogenic changes in renal tissue

Altered mRNA expression in renal biopsy tissue from patients with IgA nephropathy

Altered mRNA expression in renal biopsy tissue from patients with IgA nephropathy. Background. Immunoglobulin A (IgA) nephropathy (IgAN) is a renal disease characterized by glomerular deposition of IgA-dominant immune deposits that cause glomerular inflammation and sclerosis. Gene expression changes induced in renal tissues/cells as a result of the disease are largely uncharacterized. Methods. A sensitive differential mRNA display technique, restriction endonucleolytic analysis of differentially expressed sequences (READS®) compared similarly processed normal renal tissue to renal biopsy RNA from patients with IgAN, minimal change disease, and necrotizing crescentic glomerulonephritis. A subset of genes with altered expression in IgAN as identified by the READS® technology was further characterized and expression levels confirmed using real-time quantitative polymerase chain reaction (RT-PCR) analysis (TaqMan®) in all RNA. Results. Initial READS® analysis showed IgAN samples have lower mRNA levels relative to normal renal tissue mRNA samples based upon total RNA as measured by ribosomal RNA. One hundred seventy-five differentially expressed non-redundant fragments were found from 860 initial candidate fragments. Twenty genes were selected for additional TaqMan® analysis, and 13 of 20 genes showed statistically different expression when comparing biopsies from normal individuals and IgAN patients. Expression differences were seen in these genes in biopsies of IgAN of differing clinical activities. Gene expression cluster analysis using the Ward method detailed disease- and gene-related clusters. Detailed examination of the promoter regions of the genes within two gene clusters revealed common gene transcriptional regulatory protein-binding sites. Conclusion. IgAN leads to significant changes in overall mRNA transcription levels within the renal tissue, in addition to gene-specific mRNA level changes. Disease-related patterns of expression were identified and gene-specific clusters suggest common mechanisms of transcriptional alteration

Altered mRNA expression in renal biopsy tissue from patients with IgA nephropathy

Altered mRNA expression in renal biopsy tissue from patients with IgA nephropathy. Background. Immunoglobulin A (IgA) nephropathy (IgAN) is a renal disease characterized by glomerular deposition of IgA-dominant immune deposits that cause glomerular inflammation and sclerosis. Gene expression changes induced in renal tissues/cells as a result of the disease are largely uncharacterized. Methods. A sensitive differential mRNA display technique, restriction endonucleolytic analysis of differentially expressed sequences (READS®) compared similarly processed normal renal tissue to renal biopsy RNA from patients with IgAN, minimal change disease, and necrotizing crescentic glomerulonephritis. A subset of genes with altered expression in IgAN as identified by the READS® technology was further characterized and expression levels confirmed using real-time quantitative polymerase chain reaction (RT-PCR) analysis (TaqMan®) in all RNA. Results. Initial READS® analysis showed IgAN samples have lower mRNA levels relative to normal renal tissue mRNA samples based upon total RNA as measured by ribosomal RNA. One hundred seventy-five differentially expressed non-redundant fragments were found from 860 initial candidate fragments. Twenty genes were selected for additional TaqMan® analysis, and 13 of 20 genes showed statistically different expression when comparing biopsies from normal individuals and IgAN patients. Expression differences were seen in these genes in biopsies of IgAN of differing clinical activities. Gene expression cluster analysis using the Ward method detailed disease- and gene-related clusters. Detailed examination of the promoter regions of the genes within two gene clusters revealed common gene transcriptional regulatory protein-binding sites. Conclusion. IgAN leads to significant changes in overall mRNA transcription levels within the renal tissue, in addition to gene-specific mRNA level changes. Disease-related patterns of expression were identified and gene-specific clusters suggest common mechanisms of transcriptional alteration

Prostaglandin D2-Mediated Microglia/Astrocyte Interaction Enhances Astrogliosis and Demyelination in twitcher

Prostaglandin (PG)