Abstract-Receptor-mediated endocytosis of oxidized low density lipoprotein (Ox-LDL) by macrophages and the subsequent foam cell transformation in the arterial intima are key events in early atherogenesis. Recently, we have identified a novel macrophage cell-surface receptor for Ox-LDL by expression cloning from a cDNA library of phorbol 12-myristate 13-acetate-stimulated THP-1 cells, designated as the scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX). Here, we examined SR-PSOX expression in human atherosclerotic lesions. Total cellular RNA and fresh frozen sections were prepared from human carotid endarterectomy specimens (from 21 patients) and directional coronary atherectomy specimens (from 11 patients). Fragments of human aortas of 2 patients without visible atherosclerotic lesions served as negative controls. Quantitative reverse transcription-polymerase chain reaction demonstrated that SR-PSOX mRNA expression was prominent in atherosclerotic lesions but undetectable in normal aortas. Immunohistochemistry showed that SR-PSOX was predominantly expressed by lipid-laden macrophages in the intima of atherosclerotic plaques in carotid endarterectomy and directional coronary atherectomy specimens, although its expression was not detectable in normal arterial wall. 9 have been identified to support cellular uptake of Ox-LDL; however, additional molecules may also be involved in the endocytosis of Ox-LDL. Recently, by expression cloning from a cDNA library of phorbol 12-myristate 13 acetate (PMA)-stimulated THP-1 cells, we have identified a novel cell-surface receptor for Ox-LDL, which has been designated the scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX). 10Human SR-PSOX is a 30-kDa type I membrane protein consisting of 254 amino acids, which does not share any structural homology with other Ox-LDL receptors. SR-PSOX can bind and internalize Ox-LDL but not a significant amount of acetylated or native LDL. Internalized Ox-LDL, in cells expressing SR-PSOX, was subjected to lysosomal degradation. SR-PSOX also recognizes phosphatidylserine, polyinosinic acid, and dextran sulfate but not polycytidylic acid or chondroitin sulfate. In addition to PMA-stimulated THP-1 cells, expression of SR-PSOX has also been shown on human monocyte-derived macrophages and murine thioglycollate-elicited peritoneal macrophages. 10 These data demonstrate that SR-PSOX is a novel class of molecule that belongs to the scavenger receptor family; however, the relation of this novel receptor to atherogenesis has not yet been clarified.In the present study, therefore, we have explored the expression of SR-PSOX in atherosclerotic lesions of human Methods Tissue SamplesFresh frozen sections (6 m) were prepared from human carotid endarterectomy specimens from 21 patients who had transient ischemic attacks or minor completed strokes before their operations, and sections were also prepared from human directional coronary atherectomy specimens from 11 patients who underwent elective percutaneou...

No abstract

Four novel peptides were isolated from the venoms of the solitary eumenine wasps Eumenes rubrofemoratus and Eumenes fraterculus. Their sequences were determined by MALDI-TOF/TOF (matrix assisted laser desorption/ionization time-of-flight mass spectrometry) analysis, Edman degradation and solid-phase synthesis. Two of them, eumenitin-R (LNLKGLIKKVASLLN) and eumenitin-F (LNLKGLFKKVASLLT), are highly homologous to eumenitin, an antimicrobial peptide from a solitary eumenine wasp, whereas the other two, EMP-ER (FDIMGLIKKVAGAL-NH(2)) and EMP-EF (FDVMGIIKKIAGAL-NH(2)), are similar to eumenine mastoparan-AF (EMP-AF), a mast cell degranulating peptide from a solitary eumenine wasp. These sequences have the characteristic features of linear cationic cytolytic peptides; rich in hydrophobic and basic amino acids with no disulfide bond, and accordingly, they can be predicted to adopt an amphipathic α-helix secondary structure. In fact, the CD (circular dichroism) spectra of these peptides showed significant α-helical conformation content in the presence of TFE (trifluoroethanol), SDS (sodium dodecylsulfate) and asolectin vesicles. In the biological evaluation, all the peptides exhibited a significant broad-spectrum antimicrobial activity, and moderate mast cell degranulation and leishmanicidal activities, but showed virtually no hemolytic activity.

BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )

MD; the J-CRT investigatorsBackground: This multicenter prospective cohort study aimed to identify both ability of echocardiographic parameters to detect cardiac resynchronization therapy (CRT) volume responders and relation of these parameters with clinical outcomes. Methods and Results:CRT responder was defined as ≥15% reduction of left ventricular (LV) end-systolic volume at 6 months. Seven echocardiographic dyssynchrony parameters were evaluated. The clinical endpoint comprised time to death from any cause or unplanned hospitalization for a major cardiovascular event. Of the 217 patients enrolled, 63 percent were classified as volume responders, in whom significantly fewer events occurred than in non-responders (log rank, P<0.001). No single echocardiographic criterion had significant power to detect volume responders, but a combining measurement of dyssynchrony between septum and LV free wall with M-mode and tissue Doppler imaging was independently associated with volume responders. In addition, this combined parameter was associated with the endpoint (hazard ratio, 0.66, 95% confidence interval 0.30-0.98, P=0.04). In contrast, left bundle branch block was identified as an independent predictor of volume responders and more strongly associated with the endpoint (hazard ratio, 0.38, 95% confidence interval 0.20-0.72, P=0.003). Conclusions:Echocardiographic parameters did not show significant power to detect CRT responders independently. (Circ J 2011; 75: 1156 - 1163

ABSTRACT. A simple method of lymphography of the thoracic duct was investigated. Using three female beagles, contrast media were administered rectally, vaginally and into the perianal tissue. The administration sites were gently massaged, and imaging was carried out at constant intervals using computed tomography and radiograph. Moreover, Indian ink was administered into the rectum mucous membrane in dogs for proof of this method of lymphography, and the lymph drainage routes were observed. The investigation showed that clear computed tomography and radiographic contrast images of the thoracic duct were obtained by subcutaneous and submucosa injection of angiography contrast medium and 3D processing of these images revealed the three-dimensional positions and course of the thoracic duct and cisterna chyli. Chylothorax is a condition in which chyle leaks into the thoracic cavity and accumulates. Symptoms include respiratory impairment, weight loss and exercise intolerance. In most cases, the etiology is unknown [4]. A number of medical and surgical treatments are currently suggested for the treatment of chylothorax. In many cases, because medical therapies are unable to resolve chylothorax completely, surgical treatment must ultimately be considered. To date, surgical treatment of chylothorax has included thoracic duct ligation [2], pleuroperitoneal shunting [11], thoracic omentalization [8], cisterna chyli ablation [6] and pericardiectomy [5], either alone or in combination with thoracic duct ligation. Thoracic duct ligation is recommended as the 1st choice among these methods [3,5]. One possible cause for the failure of thoracic duct ligation and subsequent recurrence is the occurrence mistakes in the surgery itself, such as failure to tie all of the complex tributaries into which the thoracic duct divides [1]. The thoracic duct in dogs is known to form either a single duct or multiple tributaries within the thoracic cavity after passing through the aortic hiatus, and their courses also display a complex morphology [7]. The position and course of the thoracic duct and cisterna chyli must be confirmed preoperatively when thoracic duct ligation or cisterna chyli ablation is performed, for which lymphography of the thoracic duct is of course required [1]. Current methods for performing lymphography of the thoracic duct involve the injection of contrast medium into the mesenteric lymph nodes during laparotomy under anesthesia or contrast imaging of the thoracic duct after the injection of contrast medium into the popliteal lymph node of a pelvic limb [2, 9, 10]. However, laparotomy is an invasive procedure, and reliable results cannot be obtained by percutaneous penetration of lymph nodes when the size and position of these lymph nodes are undetermined. In the present study, beagles were used to investigate new simple sites for administration of contrast media and for obtaining lymphographic images by computed tomography (CT) or radiography of the thoracic duct, which will have clinical applicability.Three healthy ...

Acute pancreatitis, an uncommon side effect of pegylated interferon α (PEG-IFN α) and ribavirin (RBV) combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN α (60, 80, and 90 μg) plus a daily oral dose of RBV (600 mg). The therapy was discontinued, however, because of the onset of acute pancreatitis (after 15 weeks, 48 weeks, and 3 weeks respectively). The drug-induced pancreatitis was diagnosed on the basis of elevated levels of amylase and lipase and the absence of other identifiable causes. High tumor necrosis factor-α was found in one patient and high interleukin-6 in the other two. The immune system stimulated by PEG-IFN and RBV combination therapy might have caused the acute pancreatitis. Further study is needed to clarify the mechanism of the onset of drug-induced pancreatitis by PEG-IFN and RBV combination therapy.

A case of an inflammatory pseudotumor of the liver in a 75-year-old female with chronic hepatitis C whose radiologic features simulated that of hepatocellular carcinoma (HCC) is presented. On imaging studies, hypervascularity by CO2 ultrasound (US) angiography, enhancement at an early phase and isodensity at a late phase by incremental dynamic computed tomography (CT), perfusion defect by CT during arteriography (CTAP), and clinical background of hepatitis C virus (HCV) infection strongly suggested HCC. A US-guided needle biopsy revealed a mainly diffuse and polyclonal proliferation of lymphocytes positive for leukocyte common antigen (pan-lymphocyte cells), L-26 (B cell lymphocytes), and UCHL-1 (T cell lymphocytes), negative for both kappa and lambda light chains and sparsely distributed neutrophils and histiocytes. No lymphoid follicles were observed. The liver tissue around this tumor showed chronic hepatitis with mild activity and mild fibrosis. These histopathologic findings suggested that the diagnosis of inflammatory pseudotumor of the liver was tenable. As it is difficult to differentiate between inflammatory pseudotumor of the liver and HCC by imaging studies alone, supplemental biopsy, where possible, should be obtained when diagnostic imaging of tumors suggesting HCC is carried out. We emphasize that histopathology is a true gold standard in the diagnosis of this disease.