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Biomedical subjects

Shashi Kant

Publications and source records attributed to Shashi Kant.

9 recordsLinked to original sources
PubMed2006

Alternative medicine use in dialysis patients: potential for good and bad!

Although alternative medicines are widely used within the general population, the extent of their use within the dialysis population is unknown. It is possible that dialysis patients may be more likely to turn towards alternative therapies in view of the chronicity of their disease. In addition, this particular patient population could be at an increased risk of toxicity from these therapies due to an absence of renal excretion. A detailed assessment of complementary and alternative medicine use in our dialysis patients revealed that 18% of our patients had used or were using some form of alternative medicine therapy. An additional 63% of our patients, however, were willing to use a complementary or alternative medication. Our results suggest that hemodialysis patients are extremely receptive to the use of such therapies and are therefore exposed to all their potential benefit and harm.

Adult↗
PubMed2006

Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5.

The extracellular-regulated kinase (ERK) 4 (MAPK4) and ERK3 (MAPK6) are structurally related atypical MAPKs displaying major differences only in the C-terminal extension. ERK3 is known as an unstable mostly cytoplasmic protein that binds, translocates, and activates the MAPK-activated protein kinase (MK) 5. Here we have investigated the stability and expression of ERK4 and have analyzed its ability to bind, translocate, and activate MK5. We show that, in contrast to ERK3, ERK4 is a stable protein that binds to endogenous MK5. Interaction of ERK4 with MK5 leads to translocation of MK5 to the cytoplasm and to its activation by phosphorylation. In transfected HEK293 cells, where overexpressed catalytically dead ERK3 is able to activate MK5, catalytic activity of ERK4 is necessary for activation of MK5, indicating that ERK4 directly phosphorylates MK5. Interestingly, ERK4 dimerizes and/or oligomerizes with ERK3, suggesting that overexpressed inactive ERK3 recruits active endogenous ERK4 to MK5 for its activation. Hence, ERK3 and ERK4 cooperate in activation of MK5.

Cell Line↗
PubMed2005

Wnt/beta-catenin signaling mediates antineoplastic effects of imatinib mesylate (gleevec) in anaplastic thyroid cancer.

CONTEXT: Dysregulation of Wnt signaling is a key step in neoplastic thyrocyte proliferation. However, it is unclear whether the selective tyrosine kinase (TK) inhibitor, imatinib mesylate, is linked to the Wnt/beta-catenin cascade and is able to modulate the pathway. OBJECTIVE: Conflicting data are reported on the therapeutic effects of imatinib in anaplastic thyroid carcinomas (ATCs), but the molecular mechanism of action is unclear. Here, we further delineated the antitumor effects and the potential efficacy of imatinib in dedifferentiated thyroid carcinomas. RESULTS: Tissue microarray of histologically proven ATCs (n = 12) demonstrated that six of 12 tumors expressed at least one of the imatinib-sensitive TKs. Similarily, imatinib-sensitive TKs were detected in seven of 10 thyroid cancer cell lines derived from metastatic papillary, follicular, and ATCs. Coimmunoprecipitation in ARO cells demonstrated a direct link between c-abl and beta-catenin. Imatinib (10 microM for 48 h) drastically reduced beta-catenin expression and redistributed it from the nucleus to the cell membrane. It stabilized adherens junctions by increasing beta-catenin/E-cadherin binding and reduced the invasive potential of thyroid cancer. Furthermore, imatinib (10 microM for 48 h) attenuated T cell factor/lymphoid enhancer factor activity, reduced cyclin D1 levels and dose-dependently suppressed thyrocyte proliferation by half without affecting apoptosis. CONCLUSION: Our data provide a molecular mechanism for the antitumor activity of imatinib that may help to develop it as a therapeutic option in a subset of ATC patients.

Antineoplastic Agents↗
PubMed2004

Scaffolding by ERK3 regulates MK5 in development.

Extracellular-regulated kinase 3 (ERK3, MAPK6) is an atypical member of the ERKs, lacking the threonine and tyrosine residues in the activation loop, carrying a unique C-terminal extension and being mainly regulated by its own protein stability and/or by autophosphorylation. Here we show that ERK3 specifically interacts with the MAPK-activated protein kinase 5 (MK5 or PRAK) in vitro and in vivo. Expression of ERK3 in mammalian cells leads to nuclear-cytoplasmic translocation and activation of MK5 and to phosphorylation of both ERK3 and MK5. Remarkably, activation of MK5 is independent of ERK3 enzymatic activity, but depends on its own catalytic activity as well as on a region in the C-terminal extension of ERK3. In mouse embryonic development, mRNA expression patterns of ERK3 and MK5 suggest spatiotemporal coexpression of both kinases. Deletion of MK5 leads to strong reduction of ERK3 protein levels and embryonic lethality at about stage E11, where ERK3 expression in wild-type mice is maximum, indicating a role of this signalling module in development.

Animals↗
PubMed2002

Putative homeodomain proteins identified in prokaryotes based on pattern and sequence similarity.

A putative homeodomain has been identified in eubacterial genomes, which include several pathogens. The domain is related in sequence to homeodomain, a component specific to transcription factors and playing a very important role in eukaryotes such as controlling the developmental processes of the organism. The putative homeodomain has been characterized utilizing the eukaryotic homeodomain protein sequence signature present in PROSITE as well as the sequence similarity search using BLAST suite for different eubacterial genomes. These findings provide evidence for the occurrence of DNA-binding motif in prokarya similar to that in eukarya.

Amino Acid Sequence↗
PubMedDate not supplied

Choices of ecosystem capital without discounting and prices.

In the last decade, neo-classical economists have used the Consumption-Growth Based Utility (CGBU) framework to suggest an appropriate discount rate for eco-system capital. The CGBU framework, being based on the simplicity and single-valued nature of man-made capital, is subject to many limitations. Three general limitations of the framework, irrespective of its use for man-made capital or ecosystem capital, paradox of consumption growth, expectations' insensitive utility specification, and insensitivity to the nature of returns, are discussed. With respect to its use for ecosystem capital, the framework has two limitations: ecosystems cannot be commoditized and ecosystem capital satisfies differentiated needs, and, hence, gross substitution between different components of ecosystem capital or between ecosystem capital and man-made capital is not possible. Therefore, the rate of discount for ecosystem capital suggested on the basis of the framework is arbitrary. In the context of international security, choices of ecosystem capital are similar to the choices of military decisions. Similar to military decisions, ecosystem choices should be made without discounting and prices. The neo-classical framework does not have appropriate tools for such decision analyses, and other streams of economics, specifically post-Keynesian economics, may assist decision-makers in analysing ecosystem choices without prices and discounting.

Conservation of Natural Resources↗