Purpose: Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. Materials and Methods: The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. Results: We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. Conclusion The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.

Ulcerative colitis is a chronic inflammatory bowel disease of unknown etiology, associated with extraintestinal manifestations, including the rarely reported immune thrombocytopenic purpura. Here, we present a case of immune thrombocytopenic purpura associated with preexisting ulcerative colitis. The patient was diagnosed with ulcerative colitis 13 years ago. Two years after diagnosis, he presented with hematochezia and active ulcerative colitis. Despite steroid use, the platelet count gradually decreased to 21,000/mm3. Hematochezia and the platelet count recovered after the administration of cyclosporine, and ulcerative colitis was in near complete remission for 11 years. However, the patient was re-admitted for hematochezia and thrombocytopenia persisting over a month. Medical management including increased doses of steroids in combination with cyclosporin failed to control hematochezia and thrombocytopenia. Immune thrombocytopenic purpura was suspected on the basis of normocellular marrow with a normal number of megakaryocytes. To treat uncontrolled colitis and steroid-refractory thrombocytopenia, total proctocolectomy with ileal pouch-anal anastomosis and splenectomy were performed. The patient was followed up for 10 months after surgery and was found to be in good health with a normal platelet count. Therefore, colectomy alone or in combination with splenectomy should be considered in cases of life-threatening ulcerative colitis complicated with steroid-refractory immune thrombocytopenic purpura.
Bone Marrow ; Colectomy* ; Colitis ; Colitis, Ulcerative* ; Cyclosporine ; Gastrointestinal Hemorrhage ; Humans ; Inflammatory Bowel Diseases ; Megakaryocytes ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic* ; Splenectomy* ; Steroids ; Thrombocytopenia ; Ulcer*

BACKGROUND: The activation of guanine nucleotide binding protein-coupled receptors, such as adenosine receptor (ADR) and opioid receptor (OPR), protects the heart against ischemia and reperfusion injury. We hypothesized that ADR or OPR might be involved in polyphenol (-)-epigallocatechin gallate (EGCG)-induced cardioprotection. METHODS: Langendorff perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Hearts were treated with 10 microM of EGCG, with or without the ADR or OPR antagonist at early reperfusion. Infarct size measured with 2,3,5-triphenyltetrazolium chloride staining was chosen as end-point. RESULTS: EGCG significantly reduced infarct volume as a percentage of ischemic volume (33.5 +/- 4.1%) compared to control hearts (14.4 +/- 1.1%, P < 0.001). A nonspecific ADR antagonist 8-(p-sulfophenyl) theophylline hydrate (27.1 +/- 1.9%, P < 0.05 vs. EGCG) but not a nonspecific OPR antagonist naloxone (14.3 +/- 1.3%, P > 0.05 vs. EGCG) blocked the anti-infarct effect by EGCG. The infarct reducing effect of EGCG was significantly reversed by 200 nM of the A1 ADR antagonist DPCPX (25.9 +/- 1.1%, P < 0.05) and 15 nM of the A2B ADR antagonist MRS1706 (29.3 +/- 1.7%, P < 0.01) but not by 10 microM of the A2A ADR antagonist ZM241385 (23.9 +/- 1.9%. P > 0.05 vs. EGCG) and 100 nM of the A3 ADR antagonist MRS1334 (24.1 +/- 1.8%, P > 0.05). CONCLUSIONS: The infarct reducing effect of EGCG appears to involve activation of ADR, especially A1 and A2B ADR, but not OPR.
Adenosine ; Animals ; Catechin ; Guanine ; Heart ; Ischemia ; Myocardial Infarction ; Naloxone ; Purines ; Rats ; Receptors, Opioid ; Receptors, Purinergic P1 ; Reperfusion ; Reperfusion Injury ; Tetrazolium Salts ; Theophylline ; Triazines ; Triazoles ; Xanthines

Left ventricular hypertrabeculation/noncompaction (LVHT) is an uncommon type of genetic cardiomyopathy characterized by trabeculations and recesses within the ventricular myocardium. LVHT is associated with diastolic or systolic dysfunction, thromboembolic complications, and arrhythmias, including atrial fibrillation, ventricular arrhythmias, atrioventricular block and Wolff-Parkinson-White syndrome. Herein, we describe a patient who presented with heart failure and wide-complex tachycardia. Echocardiography showed LVHT accompanied with severe mitral regurgitation. The electrophysiologic study revealed a fasciculo-ventricular accessory pathway and atrial flutter (AFL). The AFL was successfully treated with catheter ablation.
Arrhythmias, Cardiac ; Atrial Fibrillation ; Atrial Flutter ; Atrioventricular Block ; Cardiomyopathies ; Catheter Ablation ; Echocardiography ; Heart Failure ; Humans ; Isolated Noncompaction of the Ventricular Myocardium ; Mitral Valve Insufficiency ; Myocardium ; Pre-Excitation, Mahaim-Type ; Tachycardia ; Wolff-Parkinson-White Syndrome

Aortic coarctation is usually diagnosed and repaired in childhood and early adulthood. Survival of a patient with an uncorrected coarctation to more than 70 years of age is extremely unusual, and management strategies for these cases remain controversial. We present a case of a 75-year-old woman who was first diagnosed with aortic coarctation and severe aortic valve stenosis 5 years ago and who underwent a successful one-stage repair involving valve replacement and insertion of an extra-anatomical bypass graft from the ascending to the descending aorta.
Aged ; Aorta, Thoracic ; Aortic Coarctation ; Aortic Valve Stenosis ; Female ; Humans ; Thoracic Surgical Procedures ; Transplants

BACKGROUND: Characterization of clinical features of bacteremic severe sepsis acquired from the community has been inadequate; therefore, our goal in this study was to identify prognostic factors associated with outcome in patients with community-acquired bacteremic severe sepsis. MATERIALS AND METHODS: Adult patients (> or =18 years) with community-acquired severe sepsis in whom pathogens were identified from blood cultures were included in the study. Data were collected prospectively from 12 teaching hospitals between May, 2005, and February, 2009. Data included demographic characteristics, co-morbid medical conditions, primary infection sites, sepsis severity, mortality, causative microorganisms, and the appropriateness of initial empirical antibiotic therapy. RESULTS: During the study period, 1,152 patients were diagnosed with community-acquired severe sepsis and 422 patients were found to harbor pathogens in their blood. Among the 422 patients analyzed, 253 (60.0%) patients went into shock and 121 patients (28.7%) died during hospitalization. Risk factors, including respiratory tract infection (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.11-6.09), number of organ dysfunctions (OR, 1.39; 95% CI, 1.13-1.71), and higher APACHE II scores (OR, 1.08; 95% CI, 1.03-1.13) showed an association with poor survival, whereas Escherichia coli as a pathogen (OR, 0.31; 95% CI, 0.16-0.64) showed an association with lower mortality. CONCLUSIONS: In addition to severity of illness, the primary site of infection and causative microorganisms were also identified as important prognostic factors in patients with community-acquired bacteremic severe sepsis.
Adult ; APACHE ; Bacteremia ; Community-Acquired Infections ; Escherichia coli ; Hospitalization ; Hospitals, Teaching ; Humans ; Prospective Studies ; Respiratory Tract Infections ; Risk Factors ; Sepsis ; Shock ; Shock, Septic

In surgeries that require the implantation of a pacemaker, the endocardial pacemaker leads are introduced into the cardiac chambers through subclavian or axillary venous catheterization or cephalic vein cutdown. The drawback of this type of surgery is scarring of the pectoral area, which can be a serious cosmetic problem especially for young women. In this study, we report on 2 cases where a permanent pacemaker in two young women with symptomatic bradycardia was implanted using a transaxillary incision. Both patients successfully recovered with no complications and were asymptomatic for more than 17 months after the procedure. Therefore, we found that implantation of a pacemaker via transaxillary incision provided excellent cosmetic results and should be considered in young women that require this type of surgery.
Axilla ; Bradycardia ; Catheterization ; Catheters ; Cicatrix ; Cosmetics ; Female ; Humans ; Venous Cutdown

BACKGROUND/AIMS: We examined the ischemia-modified albumin (IMA) level during exercise in patients with coronary artery disease (CAD). METHODS: Forty patients with a history of chest pain underwent both symptom-limited treadmill exercise stress testing and coronary angiography within one week. During the treadmill tests, blood samples were obtained at baseline and 5 min after exercise to measure the serum IMA level. RESULTS: Of the 40 patients, fourteen (35%, CAD group) had significant coronary artery stenosis, while the other 26 (65%, non-CAD group) did not. The baseline and post-exercise IMA levels in the two groups did not differ significantly (105.2+/-7.2 vs. 107.7+/-6.7 U/mL at baseline and 93.1+/-10.1 vs. 94.8+/-5.7 U/mL at post-exercise in the CAD and non-CAD groups, p=0.29 and 0.57, respectively). The changes in IMA after exercise did not differ either (-10.4+/-7.5 vs. -14.0+/-7.6 U/mL in the CAD and non-CAD groups, respectively, p=0.10). Similarly, the change in IMA between the exercise ECG test positive (TMT positive, n=9) and negative (TMT negative, n=20) groups did not differ (-14.63+/-5.19, vs -8.50+/-9.01 U/mL, p=0.15, in the TMT positive and negative groups, respectively). CONCLUSIONS: Our results suggest that IMA has limitation in detecting myocardial ischemia during symptom-limited exercise stress tests.
Aged ; Albumins/*diagnostic use/metabolism ; *Chest Pain ; Electrocardiography ; *Exercise Test/instrumentation ; Female ; Humans ; Lactic Acid/blood ; Male ; Middle Aged ; Myocardial Ischemia/blood/*diagnosis/physiopathology ; Pilot Projects

We report here on the use of the Venture(TM) catheter to facilitate successful advancement of a guidewire across difficult, complex lesions after the prior attempts at guide wire passage were unsuccessful with using standard wires. This Venture(TM) catheter may increase the success rate and reduce the procedural time for such a challenging interventional procedure.
Angioplasty ; Catheters

PURPOSE: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the develoopement of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-beta-D-arabino-furanosyl-5-[124/125I]iodo- uracil ([124/125I]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. MATERIAL AND METHODS: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [125I]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [124I]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. RESULTS: Specific accumulation of [125I]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [125I]FIAU uptake was linearly correlated (R2=0.964, p=0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [125I]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small aninal PET, [124I]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. CONCLUSION: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.
Animals ; Arabinofuranosyluracil ; Carcinoma, Hepatocellular ; Cell Count ; Cell Line ; Genes, Reporter ; Genetic Therapy ; Herpes Simplex ; Herpesvirus 1, Human ; Humans ; Liver ; Liver Neoplasms, Experimental ; Methylmethacrylates ; Mice ; Polystyrenes ; Simplexvirus ; Statistics as Topic ; Uracil ; Ursidae