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A 52-year-old man with consciousness disorder following a 2-day history of general fatigue, diarrhea, vomiting and excessive thirst was admitted to our hospital. Severe hyperglycemia (1,739 mg/dL) with a slightly elevated HbA1c level (6.9%), ketonuria and low C-peptide level (0.07 ng/mL) confirmed the diagnosis of fulminant type 1 diabetes mellitus (FT1DM). Following sudden unexplained cardiogenic shock shortly after the initiation of insulin therapy with no evidence of myocardial ischemia assessed by coronary angiography, the patient was supported with percutaneous venoarterial extracorporeal membrane oxygenation. Electron microscopic analysis of the myocardium revealed massive lipid droplets without the infiltration of inflammatory cells. His left ventricular function began to recover during the following days and returned to a normal level on day 14. Currently, the impact of FT1DM on intramyocardial lipid deposition is poorly understood. However, this case suggests that even short-term exposure to high concentrations of glucose can be responsible for lipotoxicity followed by severe cardiac dysfunction.

Spontaneous cholesterol embolization is thought to be due to aortic plaque-derived shower emboli; however, flowing cholesterol crystals have not been detected. Free multilayer cholesterol crystals obtained from the femoral artery were observed using polarized light microscopy. Detection of these crystals may indicate the occurrence of spontaneous shower emboli. (Level of Difficulty: Intermediate.), Graphical abstract, Spontaneous cholesterol embolization is thought to be due to aortic plaque-derived shower emboli; however, flowing cholesterol crystals have not been…

Recent advances in non-obstructive general angioscopy (NOGA) have enabled the detection of aortic atherosclerosis. The incidence of spontaneous ruptured aortic plaques (SRAPs) and aortic injuries was found to be high in patients diagnosed with or suspected of having coronary artery disease. These facts may result in a paradigm shift for diseases such as aging and acute aortic syndrome because the incidence of systemic embolic diseases and aortic disease are assumed be high. Aortic thromboembolism has been thought to be mainly iatrogenic and is referred to as "cholesterol embolization syndrome" or "cholesterol crystal embolization", although the cholesterol crystals (CCs) were not demonstrated routinely as real images. Atheromatous materials, fibrins, calcifications, macrophages, and a mixture of such substances are released through a puff or puff-chandelier rupture. Among atheromatous materials, CCs can be easily detected clinically in sampled blood via polarized light microscopy. Atheromatous materials include rich CCs and free monolayers, and multilayer CCs are released when the atheromatous materials from vulnerable plaques break into pieces, such as in puff or puff-chandelier rupture. Released SRAPs seem to be asymptomatic; however, accumulation of SRAPs referred to as accumulated spontaneous asymptomatic plaques may cause aging through systemic "embolic" processes, such as mechanical obstruction and an inflammasome pathway. Unique findings in "atherosclerotic" acute aortic syndrome, such as a clear boundary between the dissected lesion and the normal lesion, fissure/fissure bleeding suggesting an entry or a reentry, and subintimal blood flow detected through NOGA are reported. Fissure/fissure bleeding and subintimal blood flow may be the first or last triggers of "atherosclerotic" acute aortic syndrome. Pre-emptive diagnosis and risk stratification of acute "atherosclerotic" aortic dissection and feedback for endovascular therapy may be enabled through the use of NOGA in the future.

Coronary stenting was performed for a 76-year-old patient with acute coronary syndrome with severe stenosis of the right coronary artery. Puff rupture including cholesterol crystals was detected on nonobstructive general angioscopy. One month after intervention, continuous release of cholesterol crystals was found despite successful percutaneous coronary intervention. (

Objective Nonobstructive general angiography (NOGA) is a novel modality to detect and sample spontaneous ruptured aortic plaques (SRAPs). We aimed to establish novel methods to detect cholesterol crystals (CCs) in sampled SRAPs. Methods Blood specimens containing SRAPs were obtained from patients using NOGA. Blood was instantly frozen on a glass slide and subsequently thawed for quantitative analysis and spread onto a filter paper that was rinsed using distilled water. Qualitative analysis was performed for the rinsed water using polarized light microscopy, and the filter paper was embedded in paraffin for histologic analysis. Results The CCs were clearly observed after hemolysis using the instant freeze-thaw method. The filter paper rinse method indicated free CCs of varying shapes under polarized light microscopy without erythrocytes. On the filter paper, sampled SRAPs showed Lamé-like small particles. Histopathology revealed various atheromatous components. Conclusion A set of novel methods for detecting CCs from sampled blood was established.

Development and expansion of cholesterol crystals (CCs) within a lipid rich atherosclerotic core are believed to predispose to plaque rupture. We have used non-obstructive general angioscopy to described a range of appearances of spontaneously ruptured atherosclerotic plaques (SRAPs) in the aorta in-situ, and have confirmed that debris extruding from some SRAPs (puff-chandelier lesions) are rich in cholesterol crystals and leukocytes. The purpose of this study was to characterized the nature of the inflammatory infiltrate of this debris.Debris was collected from puff-chandelier lesions at the time of angioscopy in patients with known coronary disease. Prepared specimens were examined by light microscopy, and immunostaining was used to detect markers of activation of the innate inflammatory pathway including CD68, NLRP3, caspase-1, IL-1β, IL-18, and IL-6.We analysed debris sampled from 20 puff-chandelier lesions. Microscopy confirmed the presence of large CCs, macrophages, fibrin, calcified gruel, lymphocytes, and neutrophils in 100%, 100%, 95%, 25%, 20%, and 15% of the specimens respectively. Immunostaining confirmed the presence of CD68, NLRP3, IL-1β, and IL-6 within the debris in 100%, 90%, 80%, and 80%, of the specimens respectively. CCs, NLRP3, caspase-1, IL-1β, IL-18, were also identified in the cytoplasm of macrophages.Debris from SRAPs with a puff-chandelier appearance invariably contained large CCs associated with a range of activated leukocytes involved in innate inflammation. This observation supports the thesis that the development and enlargement of CCs in the core of lipid rich plaques may precipitate traumatic and inflammatory injury that may lead to plaque rupture.

An autopsy case of chronic Chagas disease, a debilitating disorder caused by persistent infection by protozoa, Trypanosoma cruzi (Tr. cruzi), is reported. The patient was a 73-year-old Brazilian woman of Japanese descent, who had emigrated to Japan at the age of about 40 years. She died of chronic cardiac insufficiency about 8 years after the onset of cardiac symptoms. At autopsy, the heart showed typical features of chronic Chagastic cardiomyopathy: chronic lymphocytic myocarditis with extensive fibrosis and the formation of an apical aneurysm. The pathogenic protozoa were not detected in the cardiac tissue. The kidney showed typical features of membranoproliferative glomerulonephritis (MPGN). On the basis of experimental data which suggested that chronic infection of Tr. cruzi could elicit immune complex-mediated glomerulonephritis, we considered that the chronic persistent infection by Tr. cruzi contributed to the pathogenesis of MPGN in this patient.

Background Non-obstructive general angioscopy (NOGA) can be used to diagnose aortic atherosclerotic plaques. We examine the association between the number of aortic plaques detected by NOGA and the risk of subsequent cardiovascular events. Methods The Evaluation of AtheroScleroTic and rupture events by Non-Obstructive General Angioscopy (EAST-NOGA) was a prospective cohort study of patients with suspected coronary artery disease who underwent NOGA. Results Of the 577 patients who underwent NOGA, 532 (92%) completed the follow-up (median follow-up: 13 months, interquartile range: 12-16). The median number of plaques per person was 6 (interquartile range: 3-12), and 567 (98%) had at least one aortic plaque. During the 13-month follow-up, 38 (7.1%) patients had a primary composite endpoint [including cardiovascular death, myocardial infarction, stroke, peripheral artery disease (PAD), or worsening renal function], which was significantly associated with chronic kidney disease, a history of PAD, a lower hemoglobin level, and large numbers of aortic plaques [11 (5-17) vs. 6 (2-11), p = 0.003]. A receiver operating characteristic curve analysis for the number of aortic plaques predicting composite endpoints revealed that the cut-off value of aortic plaques was 12. After multivariate adjustment, the presence of ≥12 aortic plaques remained a significant predictor for composite endpoint events (hazard ratio 2.53, 95% confidence interval 1.26-5.04, p = 0.010). Conclusions The number of aortic plaques detected by NOGA may predict subsequent clinical events.

Background: Although aortogenic stroke is recognized as one of the embolic strokes, examinations to identify the embolic source has been insufficient. Recently, non-obstructive general angioscopy (NOGA) has developed to be applied to observe atheromatous change of aorta. NOGA can help visualize the in vivo surface of aorta and plaques in detail. Methods: We examined the 114 consecutive patients whose aorta was observed by NOGA and ischemic stroke lesions were searched by brain MRI. The evaluation of the aortic observation by NOGA was defined as the presence and location of spontaneous ruptured aortic plaque (SRAP). The ascending aorta and arch were defined as proximal aorta (PAo), which ranges from the origin of the aorta to the left subclavian artery. The segment from the left subclavian artery to the height of the 5th thoracic vertebra was defined as the proximal descending aorta (DAo). Findings: Forty-nine of 114 patients included in the study had SRAP observed by NOGA. Of those, 24 patients had SRAP in PAo, and 43 had SRAP in DAo. Patients with ischemic stroke had a significantly higher frequency of SRAP detection than those without ischemic stroke (69% vs. 33%, p

Sporadic gastrin-producing neuroendocrine tumors (NETs) of the duodenum present with either Zollinger-Ellison syndrome or unspecific syndromes. Ki-67 scoring in cytopathology is an alternative approach for establishing the gastrinoma grade. Although the majority of NETs, including gastrinomas, occur in the duodenum, most research regarding the Ki-67 index is focused on tumors of pancreatic origin. To the best of our knowledge, there is no study on the Ki-67 index for cytological analysis of duodenal gastrinoma. The current report presents two cases of a 56-year-old man and a 66-year-old woman with NET G1 and G2 gastrinoma, respectively, arising in the duodenal bulb. The present report focused on the differences in nuclear pleomorphism and Ki-67 index between these two cases.

Background Spontaneous ruptured aortic plaques (SRAP), which might cause atheromatous embolization, are thought to be mainly iatrogenic and have not been observed directly. Objectives The purpose of this study was to clarify the incidence, types, and dimensions of SRAP using angioscopy. Methods In a cross-sectional study, 324 consecutive patients diagnosed with or suspected of having coronary artery disease were subjected to intra-aortic scans with nonobstructive angioscopy. Samples of SRAP were taken from the aorta. The dimensions of cholesterol crystals of atheromatous materials were measured with a polarizing microscope and compared with those of the ghost images of cholesterol crystals. Results SRAP were detected in 262 patients (80.9%); 120 of 262 patients had ruptured aortic plaques below the diaphragmatic level. Samples were successfully obtained from 96 patients. The detected numbers of atheromatous material, fibrin, macrophage, and calcification were 237 (49.1%), 244 (50.6%), 111 (23.0%), and 127 (26.3%) out of 482 samples, respectively. The median lengths and widths of the sampled plaques were 254 μm (interquartile range [IQR]: 100 to 685 μm) and 148 μm (IQR: 535 to 423.5 μm), respectively. The lengths and widths of the cholesterol crystals isolated from atheromatous materials were 40 μm (IQR: 32.7 to 53.7 μm), and 30 μm (IQR: 23 to 38 μm), respectively, compared with the respective dimensions of the ghost images of 86 μm (IQR: 53 to 119) and 13 μm (IQR: 7 to 18 μm). No embolic symptoms were observed within 24 h of general care via cardiac catheterization. Conclusions SRAP are commonly scattered, and their dimensions were smaller than previously recognized. (Detecting Ruptured Aortic Plaques by Nonobstructive Angioscopy; UMIN000029772)

Non-obstructive angioscopy (NOA) is used to visualize the surface of the coronary artery, and a clear visual field is obtained by injecting transparent fluid into the gap between the probing catheter and the fiber. This study examines visual field expansion by a dual infusion method, which involves an infusion from the probing and guiding catheters, and the relationships between visual grade and vessel characteristics. Thirty-two patients and thirty patients performed coronary plaque analysis with NOA using the conventional method and the novel dual infusion method, respectively. Images were blindly analyzed retrospectively. Visual fields were assessed from image slices using a 5-point scale (0 = invisible, 1 = poor, 2 = adequate, 3 = good, 4 = excellent) at 5-s intervals. The relationships between visual grade and vessel characteristics were analyzed using multiple stepwise linear regression analysis. The mean visual grade, “excellent” ratio, and “adequate” ratio were significantly higher using the dual infusion method than those obtained using the conventional method (p = 0.003, p = 0.004, and p = 0.005 respectively). The “invisible” ratio was significantly lower using the dual infusion method than the conventional method (p = 0.027). The visual field was negatively associated with the conventional method (β = −0.154, p

Generally, in acute myocardial infarction, the plaque rupture site is around the occluded site. In this case, coronary angioscopy effectively detected a rupture at a nonstenotic lesion, and the consequent thrombotic occlusion may lead to acute myocardial infarction apart from rupture. Aspirated plaques contained atheromatous materials, cholesterol crystals, and fibrin. (Level of Difficulty: Intermediate.), Generally, in acute myocardial infarction, the plaque rupture site is around the occluded site. In this case, coronary angioscopy effectively detected…

Background The major concerns with coronary computed tomography angiography (CCTA) is the amount of contrast media (CM) injected and the radiation dose. Purpose To establish low radiation CCTA with low amount of contrast media. Methods Consecutive 60 patients (body weight ≤70mg or less and Agatston score ≤400) who were scheduled coronary computed tomography angiography were enrolled. Dual-source scanner (SOMATOM Force, Siemens, Germany) was used and CM used was Iopamidol 370mg/I (Bayer, Germany). Coronary CT angiography was performed with Turbo Flash Spiral and Sinogram Affirmed Iterative Reconstruction was done. The dose of contrast media was decided according to our original predicting system for 300HU. This study was approved by the local ethics committee and all patients gave written, informed consent. Exclusion criteria for CCTA were low Agatston score ( Results All patients successfully performed CCTA. Age averaged 46±15 yo (mean±S.D.) and body mass index averaged 22.5±3.0. Used CM was 12±7ml and intracoronary CT number 329±28HU. Dose-length product averaged 21.7±15.0 mGy cm and effective dose averaged 0.30±0.21mSv. Image quality averaged 4.8±0.7. CCTA with the lowest effective dose was 0.04mSv and CCTA with the lowest CM was 4ml. Conclusions Ultra-low dose 70kV-CCTA with low dose of contrast media can be performed using dual source computed tomography in patients with body weight ≤70mg or less and Agatston score ≤400.

Background Cholesterol crystals (CCs) have been recognized as only ghost images. Recently, free monolayer and multilayer CCs besides atheromatous materials from aortic ruptured plaque, obtained using nonobstructive angioscopy, were demonstrated using polarized light microscopy. Purpose The aim of the study was to detect free CCs from coronary slow flow. Methods A total of 86 patients with coronary artery disease underwent angioscopy with coronary artery sampling. Blood in the coronary artery with and without temporary slow flow was sampled. The blood sample was spread onto a filter paper, and the filter paper was rinsed with distilled water (filter paper-rinse method). The rinse water was scanned using polarized light microscopy, and CCs were detected. The dimensions of CCs from the coronary artery and aortic ruptured plaques were measured for 100 randomly selected samples. The lengths and widths of the CCs were measured. Results CCs were obtained in 31 of 86 patients (36.0%). CCs were detected in 38.4% of patients with acute coronary syndrome and in 31.9% of patients with stable angina. CCs were detected 47.1% with slow flow and in 25% without slow flow. Cholesterol Crystals in Coronary Artery Conclusions CCs from the coronary artery can be successfully obtained by using our original method. CCs were detected in patients with clinically stable angina and in those without coronary artery slow flow.

Background Non-obstructive general angioscopy has enabled to demonstrate high incidence of various types of spontaneous ruptured aortic plaques/injuries (SRAPIs). Purpose The aim of the study is to clarify the relationship between SRAPI and cardiovascular risk factors. Methods A total of 439 consecutive patients who had or suspected coronary artery disease were performed angioscopy and were screened SRAPI from ascending aorta to iliac artery. The incidence and the number of SRAPI were analyzed. Association between the total number of total SRAP and patients' characteristics were analyzed. Results The total number of SRAPI detected was 2211, 10 [4,22](median [IQR]) per patient. The numbers of high incidence of representative SRAPI, such as erosion, intramural bleeding, puff-chandelier rupture, puff rupture, fissure, flap, bleeding from fissure, and subintimal bleeding were 327, 313, 268, 262, 224, 167, 120, and 91, respectively. Stepwise multiple linear regression analysis indicated that age, smoking, HbA1c, and coronary heart disease significantly affected the numbers of overall SRAPI (Table). Conclusions SRAPIs were associated with cardiovascular risk factors.

Background Giant cell arteritis (GCA) is a granulomatous vasculitis and targets large vessels with predominance for the aortic arch and the cranial branches. GCA with cranial symptoms shows headache, jaw claudication, and ophthalmologic symptoms and thus was previously called temporal arteritis. Recently, cases of GCA without cranial manifestations and extracranial GCA have been reported. Case presentation A 76-year-old woman was referred to our hospital complaining of sudden abdominal pain and high fever. Her present history of illness did not show any cranial symptoms such as headache, visual disturbance, or stroke. CT images showed severe thickening of the small intestinal mesentery and massive ascites. She was diagnosed to have acute abdomen probably with gastrointestinal perforation and underwent the emergent laparotomy. Excisions of a 60-cm length of the jejunum including the thickening mesenteric lesion were carried out. Marked hypertrophy of the vascular intima and mild stenosis of the arterial lumen were displayed with infiltration of lymphocytes, neutrophils, and eosinophils. Scattered multinucleated giant cells on the endothelium, in the intima, media, and adventitia were demonstrated. Elastica van Gieson stain showed focal loss and fragmentation of the internal elastic lamina. Histopathological examinations showed typical GCA. Her postoperative process was uneventful without any symptoms, and she was followed as an out-patient prescribed with daily doses of 40 mg of prednisolone. Conclusions We hereby report a rare case of mesenteric involvement in GCA without cranial manifestations and elucidate the histopathological features of extracranial GCA in arteries as well as veins and jejunum.

Cerebral arterial air embolism is a rare and unexpected complication of advanced esophageal cancer. The entry of air to systemic circulation is an esophago-left atrial or pulmonary vein fistula formation. Herein, we report an autopsy case of a 64-year-old man. He was diagnosed esophageal cancer 2 years ago and underwent chemotherapy and concurrent chemoradiotherapy but the disease progressed, unfortunately. Then two metal stents were inserted into the middle thoracic esophagus as a palliation of dysphagia. After initiation of oral intake, he developed deterioration of consciousness. The cranial computed tomography showed cerebral arterial air emboli with multiple low-density areas. He failed to gain consciousness again and died one and half days later. In a literature survey, this autopsy case is the first presentation that confirmed histologically the close association between stent placement and formation of esophago-left atrial fistula. Due to the fatality of cerebral arterial air embolism, clinicians should keep in mind the possibility of this catastrophic complication after multimodality treatment of esophageal cancer.

Aims Enzyme replacement therapy (ERT) has been shown to be effective in the treatment of Anderson–Fabry disease (AFD). However, there have thus far been few reports on the histological findings of the heart in cases treated with ERT for more than 10 years. We had an opportunity to examine the heart of an AFD patient that had received ERT for more than 10 years, as well as those of two other patients, by autopsy, and compare the pathological findings. Methods and results Three AFD patients who had received ERT for different durations underwent autopsy. Marked left ventricular hypertrophy was observed in all three cases. The myocardial fibrosis of the patient that had been administered ERT for more than 10 years was much slighter when compared with the remaining two cases. We further observed significant differences in globotriaosylceramide (Gb3) deposition and mitochondria in the cytoplasm of myocytes by electron microscopy. Conclusion ERT may not reduce left ventricular hypertrophy in AFD, but does prevent myocardial fibrosis when initiated before progression of fibrotic change.

We could observe the endoluminal stent graft (SG) following thoracic endovascular aneurysm repair (TEVAR) by a coronary artery angioscope and establish intravascular visualization of SG. The patient was a 70-year-old woman with the distal aortic arch aneurysm and the descending aortic aneurysm, and debranching TEVAR were performed. After 12 months follow up, urgent hospitalization was required for chest pain, and cardiac catheter examination with a coronary artery angioscope was performed. The endoluminal SG was observed. The observation in angioscope which is a video image is better than CT that is a still image, and observation in blood vessel or SG is possible. It may be possible to observe the endoluminal SG, allowing potential investigation of an endoleak, or the covering status of the SG with the native aortic vessel wall, or the state of intimal membrane formation in the endoluminal graft.

Objective: Pathologic features of atherosclerotic plaques on CT are not established. We compared CT values among pathologically confirmed plaque constituents and evaluated their ability to distinguish plaque constituents. Methods: 50 histopathological images of carotid endarterectomy samples from 10 males and 2 females (age 54–74 years, average 65.9 years) were examined. We compared pre-operative CT [pre-contrast (CT-P), early post-contrast phase (CT-E), delayed post-contrast phase (CT-D)] of lipid-rich necrotic core (NC) and fibrous tissue (F) plaque components with pathological images. The ability of features to differentiate plaque components using several discrimination techniques were compared. Results: CT values of NC and F were 36 ± 13, 45 ± 11 (mean ± standard deviation, Hounsfield unit, HU), 41 ± 17, 69 ± 18, and 44 ± 16, 70 ± 13 in CT-P (p < 0.01), CT-E (p < 0.0001), and CT-D (p < 0.0001), respectively. The threshold, sensitivity, and accuracy for distinguishing NC from F were 44 HU, 74%, and 68%; 55 HU, 85%, and 85%; and 63 HU, 92%, and 84% in CTP, CT-E, and CT-D, respectively. CT-P had lower accuracy than CT-E and CT-D (both p < 0.05), but CT-E and CT-D were similar. CT-E and CT-D yielded 90 and 91% sensitivity and accuracy, respectively in linear discrimination analysis. Conclusion: In both pre- and post-contrast CT, CT values were lower in NC than F. Although values overlapped, using two-phase post-contrast CTs improved discrimination ability. Advances in knowledge: Our findings may help to establish computer-aided diagnosis of vulnerable atherosclerotic plaques in future.

Backgroud Epstein-Barr virus (EBV) is associated with B-cell lymphoma in various conditions, such as immunodeficiency and chronic inflammation. We report an unusual case of EBV-positive diffuse large B-cell lymphoma (DLBCL) lacking the expression of many B-cell markers. Case presentation An 83-year-old man presented with a submandibular tumor. Histology of a lymph node biopsy specimen revealed diffuse proliferation of centroblast- or immunoblast-like lymphoid cells with plasmacytic differentiation. Scattered Hodgkin/Reed-Sternberg-like cells were also visible. A routine immunohistochemistry antibody panel revealed that the tumor cells were negative for B-cell and T-cell markers (i.e., CD3, CD19, CD20, CD38, CD45RO, CD79a, CD138, and Pax-5), but were positive for CD30 and MUM-1, not defining the lineage of tumor cells. The final diagnosis of EBV-positive DLBCL was confirmed based on the expression of B-cell-specific transcription factors (Oct-2 and BOB.1), PCR-based identification of monoclonal rearrangement of the immunoglobulin genes, and the presence of EBV-encoded small RNAs in the tumor cells (identified using in situ hybridization). Conclusion The downregulation of broad band of B-cell markers in the present case with EBV-positive DLBCL posed a diagnostic dilemma, as the possible diagnoses included differentiation from anaplastic large cell lymphoma and CD20-negative B-cell lymphomas. Results of immunohistochemical panel including B-cell-specific transcription factors and gene rearrangement analyses critically support the correct diagnosis.

Cholesterol crystals (CCs) have been recognized as only ghost images. Recently, free monolayer and multilayer CCs besides atheromatous materials from aortic ruptured plaque, obtained using nonobstructive angioscopy, were demonstrated using polarized light microscopy. The aim of the study was to

The relationship between spontaneous ruptured aortic plaques/injuries (SRAPIs) and peripheral artery disease (PAD) has not been elucidated. This study aimed to determine if SRAPIs may be related to PAD. A total of 440 consecutive patients with or suspected of having coronary artery disease were

Background Pulmonary vascular remodeling with idiopathic pulmonary arterial hypertension (IPAH) is associated with impaired apoptosis of pulmonary artery smooth muscle cells (PASMCs). We have reported that high-dose prostaglandin I 2 (PGI 2 ) therapy markedly improved hemodynamics in IPAH patients. The therapy is thought to reverse vascular remodeling, though the mechanism is unclear. The aim of this study is to assess proapoptotic effects of PGI 2 on PASMCs obtained from IPAH patients. Methods We investigated proapoptotic effects of PGI 2 in PAH-PASMCs by TUNEL assays, caspase-3,-7 assays and transmission electron microscopy. We examined the expression of Fas ligand (FasL), an apoptosis-inducing member of the TNF cytokine family, in PAH-PASMCs. We measured the serum FasL levels in IPAH patients treated with PGI 2 . Results TUNEL-positive, caspase-3, 7-active cells and fragmentation of the nucleus were detected in PAH-PASMCs treated with PGI 2 . The percentage of apoptotic cells induced by PGI 2 at a high concentration was higher than that induced by PGI 2 at a low concentration. PCR-array analysis revealed that PGI 2 upregulated the FasL gene in PAH-PASMCs, and we measured the FasL expression by quantitative RT-PCR and Western blotting. PGI 2 significantly increased the mRNA level of FasL by 3.98 fold and the protein level of FasL by 1.70 fold. An IP receptor antagonist inhibited the induction of apoptosis, elevation of cyclic AMP and upregulation of FasL by PGI 2 . Serum FasL level had a significant positive correlation with PGI 2 dose in IPAH patients treated with PGI 2 . Conclusions PGI 2 has proapoptotic effects on PAH-PASMCs via the IP receptor and upregulation of FasL.

An inflammatory myofibroblastic tumor (IMFT) is recognized as benign tissue proliferative response comprising a variety of inflammatory and mesenchymal cells, and presents commonly at a young age. Although it occurs most frequently in the lung, it has also been observed in other organs and tissues such as the liver, spleen, bladder, and lymph nodes. However, IMFT of the heart is rare, and previously only 38 cases have been reported in the English literature. We herein report the case of a 65-year-old woman with asymptomatic IMFT in the right ventricular outflow tract. Previously reported cases are reviewed.

A 76-year-old man underwent coronary angiography to treat unstable angina with a rest angina for a week. It revealed severe stenosis in the middle of left circumflex artery ([Figure 1A][1], arrow). Percutaneous coronary intervention was performed using a 3.0 × 15-mm Xience V stent (Abbott

Oxidative modification of low density lipoprotein (LDL) is one of the critical steps for the development of atherosclerosis and leucocyte-type 12-lipoxygenase, highly expressed in macrophages, has been suggested to play an essential role in this process. In the present study, we show that guava leaf extracts inhibited, not only the leucocyte-type 12-lipoxygenase activity, but also LDL oxidation, mediated by the enzyme-overexpressing macrophage-like J774A.1 cells. Oral administration of guava leaf extracts to apoE-knockout mice at 100 mg of dry extracts/kg of body weight, once a day for 16 weeks, significantly reduced the area of atherogenic lesions developed in the aorta and aortic sinus. The major components inhibiting leucocyte-type 12-lipoxygenase contained in guava leaf extracts were identified as ethyl gallate and quercetin. The inhibitory effects of guava leaf extracts on the leucocyte-type 12-lipoxygenase activity, as well as on cell-mediated LDL oxidation, might be involved in the antiatherogenic effect of the extracts.