Chan-Sik Park

Terahertz imaging of excised oral cancer at frozen temperature

The feasibility of terahertz (THz) imaging at frozen temperature for the clinical application of oral cancer detection was investigated by analyzing seven oral tissues resected from four patients. The size, shape, and internal position of the oral cancers were mapped by THz radiation in the frequency range of 0.2-1.2 THz at -20 °C and 20 °C, and compared with those identified in the histological examination. THz imaging of frozen tissue was found to offer greater sensitivity in distinguishing cancerous areas from surrounding tissue and a larger THz-frequency spectral difference between the oral cancer and normal mucosa than room-temperature THz imaging. A cancerous tumor hidden inside tissue was also detected using this method by observing the THz temporal domain waveform. The histological analysis showed that these findings resulted from cell structure deformations involving the invasion of oral tumor and neoplastic transformations of mucous cells. Therefore, a cytological approach using THz radiation at a frozen temperature might be applied to detect oral cancer.

Effect of αGal on corneal xenotransplantation in a mouse model

Choi HJ, Kim MK, Lee HJ, Jeong SH, Kang HJ, Park C‐S, Park C‐G, Kim SJ, Wee WR. Effect of αGal on corneal xenotransplantation in a mouse model. Xenotransplantation 2011; 18: 176–182.

Macrophage Heterogeneity of Culprit Coronary Plaques in Patients With Acute Myocardial Infarction or Stable Angina

We investigated the polarization states of macrophages in coronary atherectomy tissues retrieved from patients with acute myocardial infarction (AMI, n = 52) or stable angina pectoris (SAP, n = 22). The specimens were analyzed immunohistochemically using antibodies specific to CD11c (M1 marker), CD206 (M2 marker), and to markers of endothelial cells, macrophages, and smooth muscle cells. Baseline characteristics were similar in the 2 groups. The proportion of areas immunopositive for α smooth muscle actin was similar, but those positive for CD31 and CD68 were larger in the AMI group compared with the SAP group. In addition, AMI had significantly greater areas immunopositive for CD11c (P = .007) than did SAP, but CD206 (P = .102) positivity was not different in the 2 groups. In conclusion, M1 macrophage infiltration, not M2 macrophage infiltration, was increased in culprit plaques of patients with AMI. Macrophage heterogeneity may therefore be related to plaque instability.

Comparison of Differential Expression of P2Y12 Receptor in Culprit Coronary Plaques in Patients With Acute Myocardial Infarction Versus Stable Angina Pectoris

P2Y₁₂ receptor antagonists may have pleiotropic benefits. Little is known, however, about the expression of P2Y₁₂ receptors in coronary atherosclerotic plaques. We investigated the expression of P2Y₁₂ receptor in coronary atherectomy tissues retrieved from patients with acute myocardial infarction (AMI) or stable angina pectoris (SAP). Tissue specimens were collected from 35 patients with AMI and 19 with SAP who underwent directional coronary atherectomy. Specimens were analyzed immunohistochemically using antibodies specific to P2Y₁₂ receptor and to markers of endothelial cells, macrophages, and smooth muscle cells. The 2 groups had similar baseline clinical characteristics. Plaque types were more likely to be cellular in the AMI group. The proportion of areas immunopositive for α-smooth muscle actin was smaller but those positive for CD31 and CD68 were larger in the AMI than in the SAP group. In addition, the relative area immunopositive for P2Y₁₂ receptor was significantly larger for AMI than SAP (1.1 ± 0.9% vs 0.5 ± 0.4%, respectively, p < 0.001). P2Y₁₂ receptor positivity coincided with areas positive for CD31 and α-smooth muscle actin. In conclusion, P2Y₁₂ receptor is present in coronary atherosclerotic plaques and is increased in culprit plaques of patients with AMI. P2Y₁₂ receptor may play a role in plaque destabilization.

Effect of in vitroexpanded CD4(+)CD25(+)Foxp3(+) regulatory T cell therapy combined with lymphodepletion in murine skin allotransplantation.

A promising approach for preventing allograft rejection involves shifting the balance between cytopathic and regulatory T cells to dominance of the latter cell type. Nonspecific lymphodepletion was conducted by administration of depleting anti-CD4 and anti-CD8 antibodies to reduce effector T cells and adoptive transfer of ex vivo-expanded host Treg cells by stimulation with donor dendritic cells to augment the Treg cell compartment. Evaluation of an MHC-mismatched skin allograft model revealed that combined therapy with these two protocols consistently induced modest prolongation of allograft survival, although all skin grafts were eventually rejected. The administration of IL-2/anti-IL-2 complexes significantly improved the efficacy of combination therapy via promoting the expansion of adoptively transferred Treg cells as well as endogenous recipient Treg cells. We conclude that Treg cell therapy combined with lymphodepletion is of practical benefit for the control of allograft rejection, but requires supplementary measures to promote immune tolerance.

Comparison of ADAMTS-1, -4 and -5 expression in culprit plaques between acute myocardial infarction and stable angina

Background ADAMTS (a disintegrin and metalloproteinase with thrombospondin type 1 motifs) proteases might contribute to plaque destabilisation by weakening the fibrous cap. However, little is known about the expression of ADAMTS proteases in coronary atherosclerotic plaques. Objective To examine the expression of ADAMTS proteases in coronary atherectomy samples obtained from patients with acute myocardial infarction (AMI) or stable angina. Methods Atherectomy specimens were obtained from 34 patients with AMI (n=23) or stable angina (n=11) who underwent directional coronary atherectomy. The specimens were stained with H&E and analysed immunohistochemically using antibodies specific to ADAMTS-1, -4 and -5; versican cleavage products; and markers for endothelial cells, macrophages and smooth muscle cells. Results Baseline characteristics were similar between the two groups. The proportion of CD31 and CD68 immunopositive areas did not differ between the two groups, but the area immunopositive for smooth muscle α-actin was smaller in the AMI group. The relative area immunopositive for ADAMTS-1 in AMI (1.04% (IQR 0.59–2.09%)) was significantly greater than that in stable angina (0.24% (0.15–0.39%); p<0.001). In contrast, the proportion of areas immunopositive for ADAMTS-4 or -5 was similar in the two groups. Areas that stained for ADAMTS-1 largely overlapped with those positive for CD68 and versican cleavage products. The areas immunopositive for ADAMTS-1 were significantly correlated with CD68 immunostained areas (r=0.50, p=0.003). Conclusions ADAMTS-1, -4 and -5 were present in human coronary atherosclerotic plaques, and ADATS-1 was more strongly expressed in AMI plaques than in stable plaques. ADAMTS-1 may play a role in plaque instability.

Comparison of intravascular ultrasound and histological findings in culprit coronary plaques between ST-segment elevation and non-ST-segment elevation myocardial infarction.

It remains uncertain whether the histology of culprit coronary plaques differs between ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). We compared intravascular ultrasound (IVUS) and histologic findings in coronary culprit plaques among patients presenting with STEMI and NSTEMI. Atherectomy specimens were obtained from 96 patients, 70 with STEMI and 26 with NSTEMI, who underwent directional coronary atherectomy for de novo coronary artery lesions. IVUS examinations were performed before directional coronary atherectomy. IVUS and histologic data were analyzed. Clinical characteristics were largely similar between the 2 groups; however, normal antegrade flow before angioplasty was less frequently observed in patients with STEMI than those with NSTEMI. Plaque rupture was more common on the proximal side of the minimal lumen site. There were no differences in vessel area, lumen area, calcification, plaque burden, or remodelling index at the reference and culprit sites. However, the arc of the ruptured cavity was significantly greater in patients with STEMI than those with NSTEMI (69.4 ± 27.9° vs 51.8 ± 20.0°, respectively, p = 0.008). The proportion of atheroma, fibrocellular, and thrombus areas was not different between the 2 groups. Similarly, the relative areas immunopositive for CD31, smooth muscle α-actin, and CD68 were similar in the 2 groups. In conclusion, coronary culprit lesions in patients with STEMI show more severe plaque rupture with similar histologic features than those in patients with NSTEMI, supporting the idea that a large plaque rupture is more likely in STEMI patients.

Expression of stanniocalcin-1 in culprit coronary plaques of patients with acute myocardial infarction or stable angina

Background Stanniocalcin-1 (STC1) is involved in fundamental biological processes such as angiogenesis, inflammation and wound healing, but little is known about its expression in human coronary atherosclerotic plaques or its relationship to plaque instability. Objective STC1 expression was examined in the culprit coronary plaques of 70 patients with acute myocardial infarction (AMI; n=49) or stable angina (n=21) who underwent directional coronary atherectomy. Methods The specimens were stained with H&E, STC1-specific antibodies, and endothelial cells, macrophages and smooth muscle cell markers. Results The baseline characteristics of the two groups of patients were largely similar. CD31-immunopositive and CD68-immunopositive areas, indicative of the presence of endothelial cells and macrophages, respectively, were proportionately larger while areas immunopositive for α-actin, as a smooth muscle cell marker, were proportionately smaller in the AMI group than in the stable angina group. The proportion of STC1-immunopositive areas was significantly greater in the AMI group than in the stable angina group (20.0% (8.2–29.0%) vs 8.8% (3.9–19.4%), p=0.022). Areas positive for STC1 were independently correlated with those immunopositive for CD31 (r=0.42, p<0.001) and CD68 (r=0.40, p<0.001). STC1 immunoreactivity co-localised with CD31-immunopositive and CD68-immunopositive cells. Conclusions STC1 is differentially expressed in the culprit coronary plaques of patients with AMI versus those with stable angina. STC1 may play a role in plaque instability.

Innate immunity markers in culprit plaques of acute myocardial infarction or stable angina.

We analyzed the innate immunity markers, C-reactive protein (CRP), serum amyloid P component (SAP) and pentraxin-3 (PTX-3), and metalloproteinase-9 (MMP-9) in coronary atherectomy tissues obtained from patients with acute ST elevation myocardial infarction (STEMI) (nu2009=u200927) or stable angina (nu2009=u200915). The relative areas immunopositive for CRP and SAP were similar in the two groups. In contrast, the proportion of areas immunopositive for PTX-3 and MMP-9 was higher in the STEMI group, compared to the stable angina group. PTX-3 or MMP-9-stained areas largely overlapped with those positive for CD68. We concluded that PTX-3 plays a role in the pathogenesis of STEMI.

Aurintricarboxylic acid promotes the conversion of naive CD4+CD25− T cells into Foxp3-expressing regulatory T cells

Naive peripheral CD4(+)CD25(-) T cells can be converted into Foxp3-expressing regulatory T cells under appropriate stimulation conditions. Considering that continuous exposure to antigens is one of the prerequisites for the differentiation and maintenance of Treg cells, we investigated whether preventing activation-induced cell death while providing continuous TCR stimulation could promote the expression of Foxp3 in murine naive CD4(+) T cells. Among the several anti-apoptotic agents tested, aurintricarboxylic acid (ATA) was found to induce the in vitro conversion of naive CD4(+) T cells into Foxp3(+) Treg cells with suppressive activity. Neutralizing studies with an antibody against transforming growth factor (TGF)-β revealed that ATA requires the presence of TGF-β to induce Foxp3 expression in naive CD4(+)CD25(-) T cells. Although ATA itself did not activate the Smad signaling pathway, it down-regulated the extracellular signal-regulated kinase and mammalian target of rapamycin signaling cascade in activated T cells. Lastly, combined exposure to ATA and TGF-β had a synergistic effect on the rate of induction and maintenance of Foxp3 expression. These results indicate that ATA could be exploited to efficiently prepare inducible regulatory T cells in vitro and may aid in more precisely identifying the specific signaling pathways that drive Foxp3 expression in T cells.