Efficacy and clinical significance of omitting blue dye injection during sentinel lymph node biopsy before Mohs micrographic surgery for malignant melanoma of the lower extremities.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is usually performed using a triple technique that includes lymphoscintigraphy (LSG), which involves the injection of a radiolabelled tracer, blue dye injection, and detection of the radioisotope with a gamma probe. However, blue dye injection may cause pathological misinterpretation and obscure clinical margins, especially when combined with Mohs micrographic surgery (MMS) for cutaneous melanoma. OBJECTIVES: To assess the efficacy of SLNB without blue dye injection in patients who subsequently underwent MMS for melanomas of the lower extremities. METHODS: We evaluated patients who underwent MMS with or without SLNB using preoperative localization of the primary melanoma via LSG and intraoperative confirmation using a gamma probe between 2010 and 2016. RESULTS: Seventy-two patients with melanoma of mean Breslow thickness 3·03 ± 1·44 mm were evaluated. Sixty-five of the 72 patients underwent SLNB, the success rate of which was 98%. The 5-year overall and disease-free survival rates were 78% and 76%, respectively. CONCLUSIONS: Blue dye injection can be omitted without compromising the accuracy of standard SLNB. Omitting blue dye injection also has marked advantages in MMS for melanoma. What's already known about this topic? Sentinel lymph node biopsy (SLNB) is usually performed using a triple technique including lymphoscintigraphy, which involves the injection of a radiolabelled tracer, blue dye injection, and radioisotope detection using a gamma probe. Blue dye injection may cause pathological misinterpretation and obscure clinical margins. What does this study add? Omitting the dye does not decrease diagnostic accuracy and is particularly advantageous for Mohs micrographic surgery (MMS) in melanomas with clinically indistinct tumour borders. SLNB without blue dye injection is feasible in MMS for melanoma.

The utility of intra-operative frozen section for the evaluation of microscopic extrathyroidal extension in papillary thyroid carcinoma.

OBJECTIVES: This study was designed to evaluate the usefulness of intra-operative frozen section for the evaluation of microscopic extrathyroidal extension (ETE) in papillary thyroid carcinoma (PTC). DESIGN: Retrospective cohort study. SETTING: Dong-A University Medical Center, Busan, Korea. PARTICIPANTS: Three hundred and sixty-four patients who underwent thyroid surgery from January 2000 to December 2010 with PTC confined to one unilateral lobe as diagnosed using preoperative ultrasonography were enrolled. MAIN OUTCOME MEASURES: The patients who had microscopic ETE on frozen section were classified into "group A," and those who did not have microscopic ETE on frozen section were classified into "group B." Clinicopathologic factors including age, gender, size of the tumour, extent of operation, ETE, multifocality, bilaterality, lymph node metastasis and recurrence were compared between the two groups. RESULTS: Of the 364 patients enrolled, ETE was confirmed in 100 patients (group A, 27.5%) on frozen biopsy. The nodule size in group A (0.94±0.87 cm) was larger than that in group B (0.86±0.79 cm) (P=.042). In group A, 15 patients (15%) showed multifocality and 11 patients (14.47%) showed bilaterality. In group B, 37 patients (14.02%) showed multifocality and seven patients (43.35%) showed bilaterality. They did not differ significantly between the two groups (P=.811, P=.182). There was a higher frequency of lymph node metastases in group A (52/86, 60.47%) than in group B (7/16, 43.75%, P=.214). Recurrence was observed in only two patients who had received thyroid lobectomy as the initial surgery in group A. CONCLUSIONS: Intra-operative frozen biopsy can be a useful method for identifying the microscopic ETE. During the surgery, it can also help the surgeon to decide the optimal extent of surgery and the need for central compartment neck dissection in PTC patients.

Atypia of undetermined significance on thyroid fine needle aspiration - risk factors for malignancy.

OBJECTIVES: This study is designed to determine the clinical predictors of malignancy in the atypia of undetermined significance (AUS) category resulted from thyroid fine needle aspiration (FNA). DESIGN: Retrospective cohort study. SETTING: Dong-A University Medical Center, Busan, Korea. PARTICIPANTS: Sixty-two patients who underwent thyroid surgery from January 2010 to December 2013, following a diagnosis of AUS from preoperative thyroid FNA. MAIN OUTCOME MEASURES: We investigated the age, gender, maximum size and site of the nodules, ultrasonographic findings, cytological features, BRAF gene mutation, surgical method, number of AUS on repeated FNA and final pathologic results. RESULTS: Forty-one of sixty-two patients underwent total thyroidectomy and the rest had lobectomy. The final pathologic results were 41 malignancies and 21 benign diseases. Nodules less than 1.5 cm, ultrasonographic findings suggestive of malignancy were risk factors for malignancy on univariated analysis (P < 0.001). Multivariated analysis showed that nodules less than 1.5 cm, ultrasonographic findings suggestive of malignancy and more than 2 results of atypia from repeated FNAs were significant risk factors for malignancy (P < 0.001). A BRAF gene mutation analysis was performed in 38 patients, and 13 patients had the mutation. All patients with the BRAF gene mutation had been diagnosed with papillary thyroid cancer (P > 0.05). CONCLUSIONS: We recommend close observation or diagnostic surgery in patients with nodules <1.5 cm and with two or more malignant ultrasound feature and a BRAF mutation, or with two or more AUS findings on repeated FNAs.

Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer.

p130Cas regulates cancer progression by driving tyrosine receptor kinase signaling. Tight regulation of p130Cas expression is necessary for survival, apoptosis, and maintenance of cell motility in various cell types. Several studies revealed that transcriptional and post-translational control of p130Cas are important for maintenance of its expression and activity. To explore novel regulatory mechanisms of p130Cas expression, we studied the effect of microRNAs (miRs) on p130Cas expression in human breast cancer MCF7 cells. Here, we provide experimental evidence that miR-362-3p and miR-329 perform a tumor-suppressive function and their expression is downregulated in human breast cancer. miR-362-3p and miR-329 inhibited cellular proliferation, migration, and invasion, thereby suppressing tumor growth, by downregulating p130Cas. Ectopic expression of p130Cas attenuated the inhibitory effects of the two miRs on tumor progression. Relative expression levels of miR-362-3p/329 and p130Cas between normal and breast cancer correlated inversely; miR-362-3p/329 expression was decreased, whereas that of p130Cas increased in breast cancers. Furthermore, we showed that downregulation of miR-362-3p and miR-329 was caused by differential DNA methylation of miR genes. Enhanced DNA methylation (according to methylation-specific PCR) was responsible for downregulation of miR-362-3p and miR-329 in breast cancer. Taken together, these findings point to a novel role for miR-362-3p and miR-329 as tumor suppressors; the miR-362-3p/miR-329-p130Cas axis seemingly has a crucial role in breast cancer progression. Thus, modulation of miR-362-3p/miR-329 may be a novel therapeutic strategy against breast cancer.

Production of human papillomavirus type 33 L1 major capsid protein and virus-like particles from Bacillus subtilis to develop a prophylactic vaccine against cervical cancer.

We developed a bacterial expression system to produce human papillomavirus (HPV) type 33 L1 major capsid protein and virus-like particles from a recombinant Bacillus subtilis strain. For the first time, we have isolated self-assembled virus-like particles (VLPs) of HPV type 33 from B. subtilis, a strain generally recognized as safe (GRAS). The gene encoding the major capsid protein L1 of HPV type 33 was amplified from viral DNA isolated from a Korean patient and expressed in B. subtilis; a xylose-induction system was used to control gene activity. HPV33 L1 protein was partially purified by 40% (w/v) sucrose cushion centrifugation and strong cation exchange column chromatography. Eluted samples exhibited immunosignaling in fractions of 0.5-1.0 M NaCl. The HPV33 L1 protein was shown to be approximately 56 kDa in size by SDS-PAGE and Western blotting; recovery and purity were quantified by indirect immuno-ELISA assay. The final yield and purity were approximately 20.4% and 10.3%, respectively. Transmission electron microscopic analysis of fractions immunoactive by ELISA revealed that the L1 protein formed self-assembled VLPs with a diameter of approximately 20-40 nm. Humoral and cellular immune responses provoked by the B. subtilis/HPV33 L1 strain were approximately 100- and 3-fold higher than those of the empty B. subtilis strain as a negative control, respectively. Development of a VLP production and delivery system using B. subtilis will be helpful, in that the vaccine may be convenient production as an antigen delivery system. VLPs thus produced will be safer for human use than those purified from Gram-negative strains such as Escherichia coli. Also, use of B. subtilis as a host may aid in the development of either live or whole cell vaccines administered by antigen delivery system.

Radiosurgery for metastatic spinal tumors: follow-up MR findings.

BACKGROUND AND PURPOSE: MR imaging is the primary tool for evaluation and monitoring of spinal tumors. We retrospectively analyzed the MR imaging findings before and after SRS for metastatic spinal tumors. MATERIALS AND METHODS: We reviewed MR imaging findings on 79 metastatic spinal tumor lesions in 44 patients (29 male and 15 female)who had undergone radiosurgery between November 2003 and April 2008. Posttreatment MR imaging was evaluated retrospectively for 3 aspects: 1) changes in tumor volume; 2) changes in T2 signal intensity;and 3) changes in contrast enhancement patterns. RESULTS: With regard to tumor volume on MR images, 32 lesions(40.5%) decreased in volume (group 1), 39 (49.4%) showed no change (group 2), and 8 (10.1%) increased in volume (group 3). T2 signal intensities were unchanged in 4 lesions (type 1), homogeneously increased in 3 (type 2), and changed to a homogeneously dark signal in 4 (type 4). The T2 signal intensity was increased and inter mixed with dark signal intensity (type 3) in 68 lesions. A decrease in contrast enhancement with or without non-enhancing foci was seen in 73 lesions. A persistent homogeneous enhancement pattern was seen in all 4 of the type 1 lesions, in 1 of the 3 type 2 lesions, and in 1 of the 68 type 3 lesions. CONCLUSIONS: Main MR imaging features of locally controlled metastatic spinal tumors included no increase in tumor volume, increased T2 signal intensity with intermixed T2 dark signal intensity,and decreased contrast enhancement. Follow-up MR imaging also provided several patterns of tumor recurrence [corrected].

Versatility of right gastroepiploic and gastroduodenal arteries for arterial reconstruction in adult living donor liver transplantation.

BACKGROUND: In cases where there is severe intimal dissection in the recipient hepatic artery (HA), or if the HA has been used already and additional operations are needed due to graft rejection or arterial occlusion, an alternative is necessary. In the present study, we have reported the feasibility of using the right gastroepiploic artery (RGEA) and gastroduodenal artery (GDA) in various situations where the HA is not a feasible option. METHODS: Among 463 patients who underwent primary adult-to-adult living donor liver transplantation from January 2002 to July 2010, eight subjects required alternative vessels. Four recipients displayed severe intimal injury associated with previous transarterial chemoembolization (TACE); two, required a salvage operation due to hepatic artery thrombosis (HAT); and two, retransplantations due to chronic rejection. The RGEA was used in five and the GDA in three patients. RESULTS: Postoperative Doppler ultrasonography and three-dimensional computed tomography showed patent arterial flow in all patients. However, HAT recurred in one patient who underwent a salvage operation with the RGEA; she died 2 months later. Two other patients died due to wound infection and respiratory failure within 3 months despite intact hepatic arterial flow. Four patients had no further complications during follow-up (mean = 33 months). CONCLUSION: Although there was a discrepancy in the diameter of the HA and the RGEA (or GDA), there was no problem with mobilization and microanastomosis. We therefore believe that these vessels can be good alternatives when the hepatic artery is unavailable.

An optical and microPET assessment of thermally-sensitive liposome biodistribution in the Met-1 tumor model: Importance of formulation.

The design of delivery vehicles that are stable in circulation but can be activated by exogenous energy sources is challenging. Our goals are to validate new imaging methods for the assessment of particle stability, to engineer stable and activatable particles and to assess accumulation of a hydrophilic model drug in an orthotopic tumor. Here, liposomes were injected into the tail vein of FVB mice containing bilateral Met-1 tumors and imaged in vivo using microPET and optical imaging techniques. Cryo-electron microscopy was applied to assess particle shape prior to injection, ex vivo fluorescence images of dissected tissues were acquired, excised tissue was further processed with a cell-digest preparation and assayed for fluorescence. We find that for a stable particle, in vivo tumor images of a hydrophilic model drug were highly correlated with PET images of the particle shell and ex vivo fluorescence images of processed tissue, R(2)=0.95 and R(2)=0.99 respectively. We demonstrate that the accumulation of a hydrophilic model drug is increased by up to 177 fold by liposomal encapsulation, as compared to accumulation of the drug at 24 hours.

Simultaneous peripheral tuberculous lymphadenitis and a tuberculous liver abscess in a hemodialysis patient.

A tuberculous liver abscess is an extremely rare condition. However, extrapulmonary tuberculosis is more common in end-stage renal disease patients. We report a 64-year-old woman on hemodialysis with liver cirrhosis. She had no evidence of pulmonary or intestinal tuberculosis on the chest radiograph, abdominal computed tomography (CT), or colonoscopy. She had fever and an enlarged right supraclavicular lymph node. A CT showed several cystic ring-enhancing nodules in the liver. Histopathologic examinations were performed on the enlarged lymph node and a cystic nodule in the liver, which revealed caseating granulomas. Systemic antituberculous therapy was started immediately. A subsequent sonographic examination of the lesion in the liver showed improvement. In end-stage renal disease patients, we should be concerned with extrapulmonary tuberculosis. The diagnosis and antituberculous therapy must be performed promptly.

Decomposition of 1,4-dioxane by photo-Fenton oxidation coupled with activated sludge in a polyester manufacturing process.

The cyclic ether 1,4-dioxane is a synthetic industrial chemical that is used as a solvent in producing paints and lacquers. The EPA and the International Agency for Research on Cancer(IARC) classified 1,4-dioxane as a GROUP B2(probable human) carcinogen. 1,4-dioxane is also produced as a by-product during the manufacture of polyester. In this research, a polyester manufacturing company (i.e. K Co.) in Gumi, Korea was investigated regarding the release of high concentrations of 1,4-dioxane (about 600 mg/L) and whether treatment prior to release should occur to meet with the level of the regulation standard (e.g., 5 mg/L in 2010). A 10 ton/day pilot-scale treatment system using photo-Fenton oxidation was able to remove approximately 90% of 1,4-dioxane under the conditions that concentrations of 2800 ppm H(2)O(2) and 1,400 ppm FeSO(4) were maintained along with 10 UV-C lamps (240 microW/cm(2)) installed and operated continuously during aeration. However, the effluent concentration of 1,4-dioxane was still high at about 60 mg/L where TOC concentration in the effluent had been moreover increased due to decomposed products such as aldehydes and organic acids. Thus, further investigation is needed to see whether the bench scale (reactor volume, 8.9 L) of activated sludge could facilitate the decomposition of 1,4-dioxane and their by-products (i.e., TOC). As a result, 1,4-dioxane in the effluent has been decreased as low as 0.5 mg/L. The optimal conditions for the activated sludge process that were obtained are as follows: DO, 3-3.5 mg/L; HRT, 24 h; SRT 15 d; MLSS, 3,000 mg/L. Consequently, photo-Fenton oxidation coupled with activated sludge can make it possible to efficiently decompose 1,4-dioxane to keep up with that of the regulation standard.

Percutaneous insertion of Zilver stent in malignant biliary obstruction.

BACKGROUND: We evaluated the clinical efficacy and technical feasibility of the percutaneously inserted self-expandable nitinol stent (Zilver stent) for palliation of malignant biliary obstruction. METHODS: Seventeen patients with malignant tumors involving the intra- or extrahepatic bile duct who presented with obstructive jaundice underwent percutaneous insertion of a self-expandable nitinol stent. We retrospectively reviewed the hospital records of patients and evaluated the technical feasibility on stent placement, complications, patient survival, and duration of stent patency. RESULTS: Percutaneous biliary stenting with 27 Zilver stents was performed in 17 patients with malignant biliary obstruction. Technical success was 95%. Malposition of the stent was encountered in one patient. Minor technical problems were encountered in two patients: the introducer tip was broken during stent insertion, so endoscopic removal was done. Mean follow-up period for the 17 patients was 182 days (range 29-485 days): nine patients died of progressive disease at a mean follow-up of 151 days (range 61-371days) after stent insertion and eight patients remained alive at the final follow-up of 216 days (range 29-485 days). The median survival period for all patients was 277 days. The stent occlusion rate was 26% and the mean patency period was 280 days. In five patients, seven stents were obstructed by tumor ingrowth and overgrowth. Stent patency rates were 100%, 100%, 75%, 61%, and 41% at 1, 2, 3, 6, and 12 months, respectively. A late complication, erosive bleeding of the hepatic artery by the stent, developed in one patient. CONCLUSION: Percutaneous biliary stenting using the nitinol stent is technically feasible and safe and clinically efficacious treatment for malignant biliary obstruction, even with a minor technical problem during stent insertion.

Immunobiologic analysis of arterial tissue in Buerger's disease.

INTRODUCTION: the cause of thromboangiitis obliterans (TAO) still remains unknown. We have reported that immunologic injury associated with T lymphocytes infiltration might be the initial etiologic mechanism in TAO. The present study was undertaken to examine further the mechanism of immune injury. METHODS: arterial walls affected by TAO were obtained from eight patients with eight non-pulsatile arteries and one patent artery. Immunohistochemical and TUNEL studies were performed for phenotyping of the infiltrating cells with CD4 (helper T cell), CD8 (cytotoxic T cell), CD56 (natural killer cell), and CD68 (macrophage), for identification of cell activation with VCAM-1 and i -NOS, for the presence of cell death with TUNEL analysis, and for inflammatory cytokine detection with RT-PCR. RESULTS: the characteristic features were luminal obliteration, together with a varying degree of recanalization. T cells infiltrated mainly in thrombus, intima, and adventita. Among infiltrating cells, CD4 T cells greatly outnumbered CD8 cells. VCAM-1 and i -NOS were expressed in endothelial cells around the intima (patent segment) or vaso vasorum (occluded segment). Endothelial cells in vaso vasorum stained positive with TUNEL. Interferon-gamma mRNA was detected in two specimens. CONCLUSIONS: our results suggest that T cell mediated immune inflammation is a significant event in the development of TAO.

Expression of NF-kappaB and cytokines in chronic rejection of transplanted murine heart.

The heart transplantation-associated accelerated graft arteriosclerosis (AGAS) is one of the major causes of cardiac allograft failure. We investigated the early time-course of expresssion patterns of cytokines, transcription factor, and its inhibitor in the intraabdominally transplanted mice hearts that differed only in the D locus of class I histocompatibility antigen. The allograft hearts were harvested at 1-3, 5, 7, 14, 28, and 42 days after the transplantation, and the expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) were examined in these specimens. The expressions of TNF-alpha and INF-gamma were observed on day 1, peaking on day 5 and 7, respectively. Activated NF-kappaB (p65) expression was present on the cytoplasm and perinuclear area in the endothelial cells of coronary arteries on day 1. The peak of translocation of NF-B from cytoplasm to nucleus appeared on day 5 in the endothelial cells, myocytes, and leukocytes within the vessels, and remained elevated until day 42. The I-kappaB expression gradually increased from day 1 until day 5, but a remarkable decrease was detected on day 7. Our data suggest that the increased expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) play an important role in inducing immune responses in the donor allograft heart and hence the blockage of the expressions might be mandatory to avoid a potential graft failure.

Light and electron microscopic analyses for ischaemia-reperfusion lung injury in an ovine cardiopulmonary bypass model.

An experiment to study the role of contact-activation leukocyte sequestration in the formation of ischaemia-reperfusion injury (I-R injury) was carried out. The study was conducted using light and electron microscopic analyses in an ovine cardiopulmonary bypass (CPB) model using a membrane oxygenator. Five adult sheep were used in the study. The CPB circuitry consisted of a roller pump and a membrane oxygenator. During CPB, flow rates ranged from 50 to 60 ml/kg/min with mild hypothermia. The CPB time was fixed at 120 min. Ten minutes after the start of CPB, total CPB was established. Thereafter, total CPB was performed for 100 min, followed by another 10 min of partial CPB. Lung biopsy specimens for light and electron microscopy were obtained from the upper lobe of the right lung before CPB, 109 min after the start of CPB (just before reperfusion) and 30 min after weaning (after reperfusion). A portion of the lung biopsy specimen was taken for a water content measurement at the same time intervals. For measuring the left and right atrial leukocyte counts, blood samples were taken before thoracotomy, 5 and 109 min after the start of CPB, and 30 and 120 min after weaning. C3a was measured before thoracotomy, 109 minafter the start of CPB, and 30 and 120 min after weaning. Plasma malondialdehyde (MDA) was checked before thoracotomy, 109 min after the start of CPB and 30 min after weaning. On both light and electron microscopic examination, mild to moderate acute lung change was observed after ischaemia-reperfusion. Interstitial oedema, leakage of erythrocytes into the alveolar space and endothelial cell swelling were the main findings. However, few neutrophils were seen. Water content of the lung showed a slight increase after the start of CPB, but there was no statistical significance. Neither significant differences in the transpulmonary gradients of leukocytes nor a significant complement activation, expressed by C3a levels, was observed. The MDA level did not display a significant change related to lung reperfusion despite an increase in MDA after the start of CPB. These findings indicate that I-R injury during CPB may not be from complement-activation leukocyte sequestration, but from another source of oxygen free radicals related to CPB.

Correlation of Fas and Fas ligand expression with rejection status of transplanted heart in human.

BACKGROUND: Activation of pro-apoptotic systems has been proven in rejection model of animal heart transplantation. The role of Fas and Fas ligand (FasL) in graft rejection is not fully understood, and the expression changes of these genes in human transplanted heart have not been elucidated. METHODS: Endomyocardial biopsy samples were taken from 13 consecutive patients undergoing heart transplantation at various times, and they were classified into rejection (REJ, grade 3A or more) and lack of rejection (TOL, grade 1B or less) by International Society of Heart and Lung Transplantation rejection grade. Semiquantitative reverse transcription-polymerase chain reaction and immunohistochemistry were performed to evaluate the status of Fas and FasL expression in each sample. RESULTS: Fas was constitutively expressed both in REJ and TOL specimens (expression levels normalized by glyceraldehyde-3-phosphate dehydrogenase expression in semiquantitative reverse transcription-polymerase chain reaction of REJ vs. TOL, 0.842+/-0.096 vs. 0.848+/-0.103, P=0.776); however, FasL expression was detected in 66% of REJ samples and 40% of TOL samples. Normalized levels of FasL expression were 0.591+/-0.494 (REJ) and 0.383+/-0.507 (TOL) (P<0.05). FasL was expressed by cardiomyocytes as well as graft-infiltrating cells. CONCLUSIONS: This up-regulation of FasL may be one of possible mechanisms of apoptosis in rejection process of human cardiac allograft.

Infantile hemangioendothelioma treated with high dose methylprednisolone pulse therapy.

Infantile hemangioendothelioma is a severe disease with a high mortality. It is characterized by multiple hemangioma affecting the skin and visceral organs. We report that high doses of methylprednisolone pulse therapy improved symptoms and signs of infantile hemangioendothelioma in a male neonate, and completely resolved the hepatic and cutaneous hemangioendothelioma on follow up.

Correlation between ICAM-1 and functional recovery of piglet myocardium with leukocyte-depleted reperfusion.

BACKGROUND: Reperfusion injury involves leukocyte-endothelial interaction mediated by cell adhesion molecules. This study was designed to determine the time course of intercellular adhesion molecule-1 (ICAM-1) expression and the functional recovery of myocardium when reperfused with leukocyte depleted whole blood. METHODS: Sixteen neonatal piglet hearts were harvested and stored with 4 degrees C cold University of Wisconsin Solution (UWS) for 12 hours. An ex vivo model consisting of an isolated working heart perfusion circuit, roller pumps, and a membrane oxygenator, was used for reperfusion. Atrial tissues were taken for staining ICAM-1. The stroke work index (SWI) was calculated during 4 hours of reperfusion. Two groups (group 1: reperfused with whole blood, group 2: with leukocyte depleted blood) were compared. RESULTS: The differences of ICAM-1 expression between group 1 and 2 were significant at 3 and 4 hours of reperfusion (p < 0.05). The differences of the mean stroke work indices were significant at 2, 3, and 4 hours after reperfusion (p < 0.05). CONCLUSIONS: Leukocyte-depleted reperfusion attenuates the expression of ICAM-1 and reduces the time-dependent functional deterioration of the myocardium. These results suggest that adhesion molecule like ICAM-1 plays a major role in deteriorating myocardial function during the reperfusion, possibly by leukocyte-mediated inflammatory process.