The high affinity selectin glycan ligand C2-O-sLex and mRNA transcripts of the core 2 β-1,6-N-acetylglusaminyltransferase (C2GnT1) gene are highly expressed in human colorectal adenocarcinomas

<p>Abstract</p> <p>Background</p> <p>The metastasis of cancer cells and leukocyte extravasation into inflamed tissues share common features. Specialized carbohydrates modified with sialyl Lewis x (sLe^x) antigens on leukocyte membranes are ligands for selectin adhesion molecules on activated vascular endothelial cells at inflammatory sites. The activity of the enzyme core 2 β1,6 <it>N</it>-acetylglucosaminyltransferase (C2GnT1) in leukocytes greatly increases their ability to bind to endothelial selectins. C2GnT1 is essential for the synthesis of core 2-branched O-linked carbohydrates terminated with sLe^x(C2-O-sLe^x). Our goal was to determine the expression profiles of C2-O-sLe^xin the malignant progression and metastasis of colorectal adenocarcinomas. The well characterized CHO-131 monoclonal antibody (mAb) specifically recognizes C2-O-sLe^xpresent in human leukocytes and carcinoma cells. Using CHO-131 mAb, we investigated whether C2-O-sLe^xwas present in 113 human primary colorectal adenocarcinomas, 10 colorectal adenomas, 46 metastatic liver tumors, 28 normal colorectal tissues, and 5 normal liver tissues by immunohistochemistry. We also examined mRNA levels of the enzyme core 2 β1,6-<it>N</it>-acetylglucosaminyltransferase (C2GnT1) in 20 well, 15 moderately, and 2 poorly differentiated colorectal adenocarcinomas, and in 5 normal colorectal tissues by using quantitative real-time polymerase chain reactions (RT-PCR).</p> <p>Results</p> <p>We observed high reactivity with CHO-131 mAb in approximately 70% of colorectal carcinomas and 87% of metastatic liver tumors but a lack of reactivity in colorectal adenomas and normal colonic and liver tissues. Positive reactivity with CHO-131 mAb was very prominent in neoplastic colorectal glands of well to moderately differentiated adenocarcinomas. The most intense staining with CHO-131 mAb was observed at the advancing edge of tumors with the deepest invasive components.</p> <p>Finally, we analyzed C2GnT1 mRNA levels in 37 colorectal adenocarcinomas and 5 normal colorectal tissues by RT-PCR. Significantly, we observed a greater than 15-fold increase in C2GnT1 mRNA levels in colorectal adenocarcinomas compared to normal colorectal tissues.</p> <p>Conclusion</p> <p>C2-O-sLe^x, detected by the CHO-131 mAb, is a tumor associated antigen whose expression is highly upregulated in colorectal adenocarcinomas and metastatic liver tumors compared to normal tissues. C2-O-sLe^xis a potentially useful early predictor of metastasis.</p

The development of mental health services within primary care in India: learning from oral history.

BACKGROUND: In India very few of those who need mental health care receive it, despite efforts of the 1982 National Mental Health Programme and its district-level component the District Mental Health Programme (DMHP) to improve mental health care coverage. AIMS: To explore and unpack the political, cultural and other historical reasons for the DMHP's failures and successes since 1947 (post-independence era), which may highlight issues for today's current primary mental health care policy and programme. METHODS: Oral history interviews and documentary sourcing were conducted in 2010-11 with policy makers, programme managers and observers who had been active in the creation of the NMHP and DMHP. RESULTS: The results suggest that the widely held perception that the DMHP has failed is not entirely justified, insofar that major hurdles to the implementation of the plan have impacted on mental health coverage in primary care, rather than faults with the plan itself. These hurdles have been political neglect, inadequate leadership at central, state and district levels, inaccessible funding and improperly implemented delivery of services (including poor training, motivation and retention of staff) at district and community levels. CONCLUSION: At this important juncture as the 12th Five Year Plan is in preparation, this historical paper suggests that though the model may be improved, the most important changes would be to encourage central and state governments to implement better technical support, access to funds and to rethink the programme leadership at national, state and district levels

Agriculture’s role in the Indian enigma: help or hindrance to the crisis of undernutrition?

In recent decades India has achieved one of the fastest economic growth rates in the world, yet its progress against both child and adult undernutrition has been sluggish at best. While this Indian variant of the so-called Asian enigma presents many puzzles, one of the puzzles pertains to agriculture's role. Many researchers and policymakers have high expectations of agriculture's potential to reduce undernutrition, despite a lack of substantive evidence. In this paper we assess this tenuous evidence base by exploring two key channels by which agricultural production conditions can influence nutritional outomes: a food consumption pathway and a maternal employment-time use pathway. We conclude with an appraisal of some possible entry points for pro-nutrition agricultural policies