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Biomedical subjects

S Prabakaran

Publications and source records attributed to S Prabakaran.

7 recordsLinked to original sources

Protein profiling of human postmortem brain using 2-dimensional fluorescence difference gel electrophoresis (2-D DIGE).

Two-dimensional gel electrophoresis (2-D GE) is a key tool for comparative proteomics research. With its ability to separate complex protein mixtures with high resolution, 2-D GE is a technique commonly employed for protein profiling studies. Significant improvements have been made in 2-D GE technology with the development of two-dimensional fluorescence difference gel electrophoresis (2-D DIGE), where proteins are first labelled with one of three spectrally resolvable fluorescent cyanine dyes before being separated over first and second dimensions according to their charge and size, respectively. When used in conjunction with automated analysis packages, this multiplexing approach can accurately and reproducibly quantify protein expression for control and experimental groups. Differentially expressed proteins can be subsequently identified by mass spectrometric methods. Here, we describe the successful application and optimisation of 2-D DIGE technology for human postmortem brain studies. This technology, especially when coupled with other functional genomics approaches, such as transcriptomics and metabolomics studies, will enhance our current understanding of human disease and lead to new therapeutic and diagnostic possibilities.

Brain Chemistry↗

Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress.

The etiology and pathophysiology of schizophrenia remain unknown. A parallel transcriptomics, proteomics and metabolomics approach was employed on human brain tissue to explore the molecular disease signatures. Almost half the altered proteins identified by proteomics were associated with mitochondrial function and oxidative stress responses. This was mirrored by transcriptional and metabolite perturbations. Cluster analysis of transcriptional alterations showed that genes related to energy metabolism and oxidative stress differentiated almost 90% of schizophrenia patients from controls, while confounding drug effects could be ruled out. We propose that oxidative stress and the ensuing cellular adaptations are linked to the schizophrenia disease process and hope that this new disease concept may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.

Brain↗

Expression of Fas ligand by microglia: possible role in glioma immune evasion.

The immune-privileged status of the central nervous system is thought to limit the application of immunotherapy for treatment of malignant brain tumors. Because the Fas pathway has been proposed to play a role in immune evasion, we examined the effect of tumor environment on the expression of Fas ligand (FasL) in a mouse glioma model. Immunoblotting revealed the expression of membrane-bound FasL to nearly double when murine G26 gliomas were propagated intracranially (IC) as compared to subcutaneously (SC). Further analysis by flow cytometry revealed microglia, which were absent in the SC tumors, to account for half of the FasL expression in the IC tumors. Interestingly, when FasL activity was inhibited in IC tumors, the proportion of tumor-infiltrating leukocytes increased three-fold, reaching the same frequency as the SC tumors. These observations suggest that microglia are a major source of FasL expression in brain tumors and possibly contribute to the local immunosuppressive milieu of malignant gliomas.

Animals↗

Adenocarcinoma of the colon as a second malignancy in a child.

Solid tumors as second malignancies are not common in children who have been managed for lymphoproliferative disorders. We report a case of adenocarcinoma (AC) of the colon as a second malignancy in a patient who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL). In children, primary AC of the colon is very rare; colonic AC occurring as a second malignancy in a child is rarer still. A case of AC of the colon following chemotherapy for ALL has not yet been published.

Adenocarcinoma↗

Botulinum neurotoxin types B and E: purification, limited proteolysis by endoproteinase Glu-C and pepsin, and comparison of their identified cleaved sites relative to the three-dimensional structure of type A neurotoxin.

Botulinum neurotoxin (NT) serotypes B and E are approximately 150 kDa proteins. Isolated from the liquid culture of Clostridium botulinum the NT type E is a single chain protein while the NT type B, from the proteolytic strain of the bacteria, is a mixture of dichain (nicked within a disulfide loop located about one-third the way from the N-terminus to the C-terminus) protein and its precursor single-chain protein. Endoproteinase Glu-C (EC 3.4.21.19) and pepsin (EC 3.4.23.1) were used for controlled digestion of NT types B and E; the amino acid residues flanking many of the cleavable peptide bonds were identified and the corresponding proteolytic fragments partially characterized. Chemical identification of 82 and 108 residues of types B and E NT, respectively, revealed that the residue 738 and 1098 in type E NT, identified as Leu and Asn, respectively, differ from those deduced from nucleotide sequences. Several fragments overlapped spanning various segments of the NT's functional domains; they appear to have potential for structure-function studies of the NT. The cleavage sites were compared with the previously determined proteolyzed sites on NT types A and E. The cleavage sites of the NT types A, B and E, all exposed on the protein surface, were scrutinized in the context of the three-dimensional structure of crystallized NT type A [Lacy, D.B., Stevens, R.C., 1999. J. Mol. Biol. 291, 1091-1104]. Detailed procedures for isolation of pure NT types B and E in large quantities (average yield 92 and 62 mg, respectively) suitable for crystallization are reported.

Amino Acid Sequence↗

Duplication of the urethra.

Accessory urethra or duplication of the urethra is a rare anomaly. The vast majority occur in the sagittal plane; however, collateral or side-by-side duplications in the absence of bladder duplication also exist. We report six cases of urethral duplications. The mode of presentation and the importance of complete examination are discussed.

Child↗