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Articles by S Han
Total Records ( 5 ) for S Han
  S Han , S. A Arnold , S. D Sithu , E. T Mahoney , J. T Geralds , P Tran , R. L Benton , M. A Maddie , S. E D'Souza , S. R Whittemore and T. Hagg

Blood vessel loss and inflammation cause secondary degeneration following spinal cord injury. Angiopoietin-1 through the Tie2 receptor, and other ligands through vβ3 integrin, promote endothelial cell survival during developmental or tumour angiogenesis. Here, daily intravenous injections with an vβ3-binding peptide named C16 or an angiopoietin-1 mimetic following a spinal cord contusion at thoracic level 9 in mice rescued epicentre blood vessels, white matter and locomotor function, and reduced detrimental inflammation. Preserved vascularity and reduced inflammation correlated with improved outcomes. C16 and angiopoietin-1 reduced leukocyte transmigration in vitro. Growth factor receptors and integrins facilitate each others’ function. Therefore, angiopoietin-1 and C16 were combined and the effects were additive, resulting in almost complete functional recovery. The treatment had lasting effects when started 4 h following injury and terminated after one week. These results identify vβ3 integrin and the endothelial-selective angiopoietin-1 as vascular and inflammatory regulators that can be targeted in a clinically relevant manner for neuroprotection after central nervous system trauma.

  J. Y Lee , A. K Park , K. M Lee , S. K Park , S Han , W Han , D. Y Noh , K. Y Yoo , H Kim , S. J Chanock , N Rothman and D. Kang

Objectives: This study was conducted to investigate the role of common variation in innate immunity-related genes as susceptibility factors to breast cancer risk in Korean women. Methods: Total 1536 single-nucleotide polymorphisms (SNPs) in 203 genes were analyzed by Illumina GoldenGate assay in 209 cases and the same numbers of controls. Both SNP and gene-based tests were used to evaluate the association with breast cancer risk. The robustness of results was further evaluated with permutation method, false discovery rate and haplotype analyses. Results: Both SNP and gene-based analyses showed promising associations with breast cancer risk for 17 genes: OR10J3, FCER1A, NCF4, CNTNAP1, CTNNB1, KLKB1, ITGB2, ALOX12B, KLK2, IRAK3, KLK4, STAT6, NCF2, CCL1, C1QR1, MBP and NOS1. The most significant association with breast cancer risk was observed for the OR10J3 SNP (rs2494251, P-value = 1.2 x 10–4) and FCER1A SNP (rs7548864, P-value = 7.7 x 10–4). Gene-based permutation and false discovery rate P-values for OR10J3 SNP (rs2494251) with breast cancer risk were also significant (P = 4 x 10–5 and 0.008, respectively). Haplotype analyses supported these findings that OR10J3 and FCER1A were most significantly associated with risk for breast cancer (P = 2 x 10–4 and 0.004, respectively). Conclusion: This study suggests that common genetic variants in the OR10J3 and FCER1A be strongly associated with breast cancer risk among Korean women.

  S Li , Y Sun , C. P Liang , E. B Thorp , S Han , A. W Jehle , V Saraswathi , B Pridgen , J. E Kanter , R Li , C. L Welch , A. H Hasty , K. E Bornfeldt , J. L Breslow , I Tabas and A. R. Tall

Rationale: The complications of atherosclerosis are a major cause of death and disability in type 2 diabetes. Defective clearance of apoptotic cells by macrophages (efferocytosis) is thought to lead to increased necrotic core formation and inflammation in atherosclerotic lesions.

Objective: To determine whether there is defective efferocytosis in a mouse model of obesity and atherosclerosis.

Methods and Results: We quantified efferocytosis in peritoneal macrophages and in atherosclerotic lesions of obese ob/ob or ob/ob;Ldlr–/– mice and littermate controls. Peritoneal macrophages from ob/ob and ob/ob;Ldlr–/– mice showed impaired efferocytosis, reflecting defective phosphatidylinositol 3-kinase activation during uptake of apoptotic cells. Membrane lipid composition of ob/ob and ob/ob;Ldlr–/– macrophages showed an increased content of saturated fatty acids (FAs) and decreased -3 FAs (eicosapentaenoic acid and docosahexaenoic acid) compared to controls. A similar defect in efferocytosis was induced by treating control macrophages with saturated free FA/BSA complexes, whereas the defect in ob/ob macrophages was reversed by treatment with eicosapentaenoic acid/BSA or by feeding ob/ob mice a fish oil diet rich in -3 FAs. There was also defective macrophage efferocytosis in atherosclerotic lesions of ob/ob;Ldlr–/– mice and this was reversed by a fish oil–rich diet.

Conclusions: The findings suggest that in obesity and type 2 diabetes elevated levels of saturated FAs and/or decreased levels of -3 FAs contribute to decreased macrophage efferocytosis. Beneficial effects of fish oil diets in atherosclerotic cardiovascular disease may involve improvements in macrophage function related to reversal of defective efferocytosis and could be particularly important in type 2 diabetes and obesity.

  A. W Johnson , S Han , A. M Blouin , J Saini , P. F Worley , M. J During , P. C Holland , J. M Baraban and I. M. Reti

Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates -amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this localization pattern, Narp knockout mice show deficits in using the current value of a reinforcer to guide behavior, a critical function of the limbic system. To help assess whether this behavioral deficit is due to impairment of synaptogenesis during development or in modulating synaptic signaling in the mature brain, we have used a dominant negative Narp viral construct which blocks trafficking of endogenous Narp to axons. Focal injection of this viral construct into the medial prefrontal cortex (mPFC) of adult mice, a region containing Narp-positive projection neurons, blocked reinforcer devaluation. Thus, these results indicate that Narp released from mPFC neurons plays a key role in mediating synaptic changes underlying instrumental reinforcer devaluation.

  S Han and L. Soylu

Accessory liver of the thoracic cavity is usually asymptomatic, and its incidental detection is extremely rare. In this study, an unusual case of an accessory liver lobe of the thoracic cavity in a 26-year-old woman is described. A chest roentgenogram and thoracic computed tomographic scan revealed a mass in the left thoracic cavity. Left posterolateral thoracotomy was performed by removing a 10 x 8 x 5 cm3 mass separated from lung. The arterial and venous supply of the mass originated from the abdomen. The diaphragm was found to be intact. The pathologist reported a normal hepatic tissue. This report presented a very rare occurrence of accessory liver in the thoracic cavity.

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