Indolent Small Intestinal CD4+ T-cell Lymphoma Is a Distinct Entity with Unique Biologic and Clinical Features

Enteropathy-associated T-cell lymphomas (EATL) are rare and generally aggressive types of peripheral T-cell lymphomas. Rare cases of primary, small intestinal CD4+ T-cell lymphomas with indolent behavior have been described, but are not well characterized. We describe morphologic, phenotypic, genomic and clinical features of 3 cases of indolent primary small intestinal CD4+ T-cell lymphomas. All patients presented with diarrhea and weight loss and were diagnosed with celiac disease refractory to a gluten free diet at referring institutions. Small intestinal biopsies showed crypt hyperplasia, villous atrophy and a dense lamina propria infiltrate of small-sized CD4+ T-cells often with CD7 downregulation or loss. Gastric and colonic involvement was also detected (n = 2 each). Persistent, clonal TCRβ gene rearrangement products were detected at multiple sites. SNP array analysis showed relative genomic stability, early in disease course, and non-recurrent genetic abnormalities, but complex changes were seen at disease transformation (n = 1). Two patients are alive with persistent disease (4.6 and 2.5 years post-diagnosis), despite immunomodulatory therapy; one died due to bowel perforation related to large cell transformation 11 years post-diagnosis. Unique pathobiologic features warrant designation of indolent small intestinal CD4+ T-cell lymphoma as a distinct entity, greater awareness of which would avoid misdiagnosis as EATL or an inflammatory disorder, especially celiac disease.     

In silico identification of viper phospholipaseA2 inhibitors: validation by in vitro,in vivo studies

Snake venom, particularly of vipers from the Indian subcontinent, contains Phospholipase A2 (PLA2) as one its constituents which is widely implicated in hemorrhagic, cardiac arrest and death. Development of inhibitors of the protein can facilitate the weakening or annihilation of the venom toxicity and save many human lives. In the present communication, our studies relate to the design and development of structure-based ligands as inhibitors of PLA2 of Viper venom. The study involves the computational approach towards evaluating a library of molecules comprising of natural products, and synthetic molecules through docking studies on the venom protein PDB ID: 1OXL (a dimer, available in the literature). In silico experiments have resulted in the identification of several of them as PLA2 inhibitors. The inhibitory effect of PLA2 by these compounds is attributed to a great extent to their interaction with the residues Phe 46 and Val47 of chain B of the target protein and hence these two residues are identified as the key contributor for the said activity. In order to validate the in silico findings, a selected panel of compounds have been tested by in vitro and in vivo experiments against the venom, which has led to the observance of significant corroboration between the wet lab and in silico findings, validating thereby the in silico approach used in the present study.     

Characterization of hydrocarbon emulsification and solubilization occurring during the growth of Endomycopsis lipolytica on hydrocarbons

A comparative characterization of the phenomena of hydrocarbon emulsification and solubilization taking place during the growth of Endomycopsis lipolytica on n-alkanes and alkenes was made. Evidence was obtained for the cellular production of different factors involved in emulsification and solubilization of hydrocarbons. It was shown that the production of these factors closely followed cell growth. The inducible nature of the alkane solubilizing factor was demonstrated using actidione as inhibitor. Whereas emulsifying factor was demonstrated using actidione as inhibitor. Whereas emulsifying factors showed a broad affinity to some particular hydrocarbons, solubilizing factor was found to be highly specific for the particular hydrocarbon on which the cells were grown. The emulsifying factor was heat stable whereas the solubilizing factor was highly unstable even at ?4°C. Metal-ion chelating agents strongly inhibited the activity of both of the factors. A crude isolate of the alkane emulsifying factor was obtained and its peptide characteristics were demonstrated. Using EDTA as an inhibitor for the emulsification–solubilization activity, evidence was obtained for the predominent role played by the emulsification–solubilization mechanism in the uptake of alkane by yeast cells.