Intra-lobar sequestration of the lung--a case report.
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Biomedical subjects
Publications and source records attributed to S Subramaniam.
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Newly synthesized eukaryotic membrane proteins must be integrated into the membrane of the endoplasmic reticulum with the correct topology to enable the subsequent acquisition of the correctly folded, functional conformation. Here, an analysis is presented of N-terminal glycosylation and steady-state membrane orientation of a series of truncation mutants of the seven-helix protein rhodopsin expressed in COS-1 cells. Mutants containing one, three, or five N-terminal transmembrane segments of rhodopsin, as well as mutants containing only the first transmembrane segment, but with hydrophilic extensions at the C-terminus were studied. The findings demonstrate that the C-terminal transmembrane segments play a crucial role in determining the final orientation of rhodopsin, and that the commitment to the correct orientation occurs only after the synthesis of at least three transmembrane segments. The experiments also suggest that the molecular machinery involved in the integration of a newly synthesized seven-helix membrane protein into the endoplasmic reticulum membrane is sensitive to the overall hydrophobicity of the sequence that follows the first transmembrane segment.
Malignant tumors are known to exhibit high rates of glycolytic activity leading to high production of lactic acid. Hence, neoplastic cells have elevated activity of enzymes responsible for glycolysis. Echitamine chloride, an indole alkaloid extracted from the bark of Alstonia scholaris, has been reported to have a highly promising anticancer activity against fibrosarcoma in rats. In the present study, the effect of echitamine chloride on energy metabolism of S-180 cells is investigated to have a better understanding on the mode of action of echitamine chloride. The effect of echitamine chloride on the mitochondrial and cellular respiration of S-180 cells was studied. Also, the effects on glucose utilization, pyruvate utilization and lactate formation were studied on whole S-180 cells and S-180 cell-free homogenate. The levels of glycolytic enzymes such as hexokinase and lactate dehydrogenase were estimated in which particular emphasis has been laid on hexokinase which occurs both in cytosolic and particulate forms in neoplastic cells. Hence the differential effect of echitamine chloride on the levels of total, cytosolic and particulate hexokinase has been investigated. In conclusion, echitamine chloride affects both cellular and mitochondrial respiration, leading to reduction of the cellular energy pool and thereby resulting in the loss of viability of S-180 cells.
CMF and radiation treatment alter the erythrocyte membrane architecture in breast cancer patients by inducing free radical formation in the system. The increased free radicals hydrolyze the unsaturated fatty acyl chains of membrane phospholipids and thus alter the membrane lipid profile. To assess the erythrocyte membrane damage caused by CMF chemotherapy and radiation treatment among breast cancer patients and to find a way which can protect them from the observed toxic manifestations form the basis of this study.
Type II diabetes is a polygenic disorder, characterized in most cases by early onset of resistance to the action of insulin. Insulin sensitizers belonging to the thiazolidinedione class offer the first therapeutic option specifically targeting the underlying insulin resistance. Troglitazone is the prototype drug of this class and has been approved for marketing in several countries. Troglitazone offers several benefits over traditional oral hypoglycemic agents such as sulfonylureas and the biguanide metformin. Most of these advantages are related to better control of glycemic parameters with troglitazone alone or when added to existing treatment. In addition, it has interesting lipid lowering activity that may be of potential benefit in reducing morbidity from cardiovascular disease among diabetics. However, troglitazone may not be the ideal insulin sensitizer since 20-30% of diabetics do not respond to it. Also, it produces liver toxicity in 2% of patients, necessitating withdrawal of the drug. A number of second generation insulin sensitizers, belonging to the same chemical class as troglitazone, are in clinical development. The role of insulin sensitizers in the management of diabetes and other diseases in which insulin resistance is an underlying feature, is likely to undergo evolution as more information is obtained from clinical studies.
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