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A 66-year-old man was diagnosed with inoperable advanced gastric cancer with liver and peritoneal metastases. The patient underwent SOX therapy as primary chemotherapy; subsequently, liver and peritoneal metastases disappeared. However, lung metastasis was detected later, and weekly paclitaxel(PTX)combined with ramucirumab(RAM)chemotherapy was initiated; subsequently, lung metastasis and advanced gastric cancer disappeared. During remission, lung metastasis was detected again. Although weekly PTX combined with RAM chemotherapy was reinitiated, a progressive disease status was achieved. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 2 weeks)was initiated for 20 courses over 11 months. This therapy was significantly effective, which aid the patient to achieve a complete response. The patient survived and is healthy for 5 years due to chemotherapy administration alone.

Controlling the crystallographic orientation of 3D photonic crystals is important as it determines the behavior of light propagating through the device. Blue phases self-assemble into unique soft 3D photonic crystals with chiral structures for circular-polarization selectivity, but it has remained a challenge to control its 3D orientation. Here, we show that the orientation of blue phases can be precisely controlled to follow a predefined pattern imprinted on a substrate by exploiting field-induced phase transitions. Obtaining the blue phase through the field-induced chiral nematic phase and tetragonal blue phase X results in a highly oriented blue phase I with the crystallographic [001] direction aligned along the surface anchoring. Our approach is applied to fabricating a Bragg-Berry hologram with omnidirectional circular-polarization selectivity, where the hologram is visible only for one circular-polarization under all incident angles. Such devices are difficult to fabricate using conventional optical materials, thereby demonstrating the potential of self-organizing soft matter for photonics. Controlling the alignment of blue phase liquid crystals is challenging. Here, electric-field induced phase transitions are exploited to control the crystal orientation of blue phase I, and applied to the fabrication of holograms with omnidirectional circular-polarization selectivity.

A 74-year-old man presented to our hospital because of anorexia. Upper gastrointestinal endoscopy revealed type 3 gastric cancer. Further examination disclosed metastasis to the perigastric lymph nodes and to the liver, and a diagnosis of non- resectable advanced gastric cancer(cT4N2H1P0M0)in cStage Ⅳ was made. A total of 4 courses of S-1 plus oxaliplatin therapy(80 mg/body/day and 100 mg/m2/cycle, respectively, for 2 weeks followed by a 1-week rest)were administered as the primary chemotherapy. Then, another metastasis to the abdominal lymph nodes and increased liver metastasis were found; thus, the patient's condition was rated as progressive disease(PD). Secondary chemotherapy comprising 10 courses of weekly nab-paclitaxel(nab-PTX)plus ramucirumab(RAM)therapy(100 mg/m2 on days 1, 8, and 15 and 8 mg/kg on days 1 and 15, respectively, every 4 weeks)were administered. Although temporary reductions in the perigastric lymph node metastasis and liver metastasis as compared with the baseline were observed, another metastasis to the abdominal lymph nodes occurred subsequently, resulting in PD. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 3 weeks) was repeated up to a total of 30 courses over 13 months. This therapy was markedly effective, achieving a near complete response. The patient is currently being followed up as an outpatient.

A male patient in his 80s, diagnosed with rectal cancer, underwent transverse colon resection(pT3, pN0, cM0, and pStage Ⅱa, RAS wild-type, BRAF-mutant). However, 19 months later, intraperitoneal metastasis was detected and the patient received 8 courses of mFOLFOX6 plus bevacizumab. Following the observation of an allergic reaction that was attributable to oxaliplatin, the regimen was changed to a total of 7 courses of sLV5FU2 plus bevacizumab. Subsequently, a marked decrease was observed in intraperitoneal metastasis. The patient completed sLV5FU2 plus bevacizumab chemotherapy. At 1 year after the marked decrease, the metastatic recurrence was not exacerbated.

The usefulness of stratum corneum neutrophil gelatinase-associated lipocalin and stratum corneum galectin-7 as biomarkers of acne vulgaris was studied. A comparison of neutrophil gelatinase-associated lipocalin levels on the cheeks of patients with acne vulgaris at the start of the study and at the time of symptom improvement showed a significant decrease. On the other hand, the galectin-7 levels at the time of symptom improvement were significantly higher than those at the start of the study. Therefore, because the inflammation in the epidermis and hair follicles was reduced after therapy, as a result of the solution of the inflammatory eruptions caused by acne vulgaris, the neutrophil gelatinase-associated lipocalin level also showed a significant decrease after therapy. These results suggest that stratum corneum neutrophil gelatinase-associated lipocalin may be useful as an objective biomarker of changes in acne vulgaris symptoms.

A 63-year-old man diagnosed with a perforated gastric ulcer and generalized peritonitis underwent surgical intervention. However, computed tomography(CT), esophagogastroduodenoscopy(EGD), and positron emission tomography-CT(PETCT) revealed an inoperable gastric cancer with liver and peritoneal metastases(cT4NxH1P1M0, cStage Ⅳ, for which he received S-1 and oxaliplatin chemotherapy[SOX therapy]). The patient underwent 10 SOX therapy cycles. Following the initial chemotherapy course, the peritoneal and liver metastases disappeared on radiographic images. However, lung metastasis was detected, and the patient initiated weekly paclitaxel(PTX)and ramucirumab(RAM)chemotherapy. After 4 treatment cycles, lung metastasis and gastric cancer disappeared.

A new cytotoxic agent designated isomethoxyneihumicin (1 and 2), a mixture of lactam-lactim tautomers, was isolated along with methoxyneihumicin (3) from the culture broth of the marine Nocardiopsis alba KM6-1. The structures of 1 and 2 were elucidated in spectroscopic analyses (1D and 2D NMR data, and ROESY correlations). Isomethoxyneihumicin (15.0 μM) and 3 (15.0 μM) arrested the cell cycle of Jurkat cells at the G2/M phase (66 and 67%) in 12 h. Isomethoxyneihumicin and 3 exhibited cytotoxicity against Jurkat cells with IC50 values of 6.98 and 30.5 μM in 20 h, respectively. These results strongly suggest that isomethoxyneihumicin and 3 exhibit cytotoxicity against Jurkat cells by inhibiting the cell cycle at the G2/M phase.

We previously reported a patient with cerebral proliferative angiopathy (CPA) who showed cerebral ischemia in resting and acetazolamide-stressed N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (123I-IMP-SPECT). At onset, the patient was treated conservatively. However, during the 2 years following initial onset, his hemiparesis and aphasia had gradually aggravated and his IQ scores were markedly decreased. MRI revealed progressive vascular proliferation and brain atrophy. 123I-IMP-SPECT showed more severely impaired cerebral blood flow (CBF) and cerebrovascular reactivity over the affected hemisphere. We performed an indirect revascularization to augment CBF; however, his neurological deficits were not improved and new arteriovenous shunts via extracranial-intracranial bypass were developed, followed by an asymptomatic small intracerebral hemorrhage. There are no reports on CPA patients who have shown cerebral hemorrhage after indirect revascularization. Treatments for CPA are still challenging and controversial. Cases with severe stenosis of the proximal arteries may benefit from indirect revascularization. But indirect bypass should not be indicated for such patients without main arterial stenosis, even if they have persistent ischemia.

A patient in his 70s was diagnosed with sigmoid colon cancer[pT3pN1cM1(PUL1), pStage IV ]for which he underwent sigmoid colectomy and received S-1 adjuvant therapy for the lung metastases. The patient received a total of 10 courses of S- 1, administered orally on days 1-14 of a 21-day cycle. The lung metastases showed a complete response, and the patient completed the S-1 chemotherapy. No recurrence of lung metastases was detected up to 6 months later.

An all-optical switch using saturable absorption that accompanies refractive-index change such as in graphene films is proposed. The switching conditions are theoretically derived for arbitrary values of absorption and refractive-index change. It is found that switching can be performed by weaker control light when the refractive-index change is accompanied in saturable absorption. Switching conditions for various combinations of absorption and refractive-index change are confirmed by FD-BPM simulation. The saturable absorption and refractive-index change in multilayered graphene sheets are also discussed based on reported experimental results.

Merkel cell carcinoma (MCC) is a highly virulent neuroendocrine cutaneous neoplasm. MCC occasionally coexists with other diseases [1]. Herein, we describe a case of MCC concurrent with squamous cell carcinoma (SCC) in the same chest nodule.A 73-year-old man presented with a 2-year history of an irregularly shaped erythematous patch on his chest. One month earlier, a painless, bleeding and rapidly growing erythematous nodule had developed on the patch. Physical examination revealed a reddish, protruding, [...]

A patient in his 70s was diagnosed with rectal cancer (pT3, pN1, cM0, and pStage IIIa) for which he underwent low anterior resection of the rectum and received adjuvant therapy with UFT/LV. Multiple liver, lung, and para-aortic lymph node metastases were detected after 6 months, and the patient then received a total of 24 courses of FOLFOX4 plus bevacizumab instead of UFT/LV. The liver and para-aortic lymph node metastases showed a complete response (CR), and the lung metastases markedly diminished. Therefore, the patient completed the FOLFOX4 plus bevacizumab chemotherapy regimen. After 2 years, a recurrence of the initial liver metastases was detected. A CR on radiological imaging does not correspond to a pathological CR. Therefore, a careful follow-upis required even when a CR on radiological imaging is achieved.

Venous thrombus is subsequently organized and replaced by fibrous connective tissue. However, the sequential changes in venous thrombi are not reliably detected by current noninvasive diagnostic techniques. The purpose of this study is to reveal whether magnetic resonance (MR) can detect venous thrombus, define thrombus age and predict thrombolytic responses. Thrombus in the rabbit jugular vein was imaged with a 1.5-T MR system at 4 h and at 1, 2 and 4 weeks using three-dimensional (3D) fast asymmetric spin echo T2-weighted (T2W) and 3D-gradient echo T1-weighted (T1W) sequences. The jugular veins were histologically assessed at each time point. Magnetic resonance imaging (MRI) was also performed in vivo before and 30 min after tissue plasminogen activator (t-PA) administration. The thrombi in MRI were comparable in size to histological sections. The signal intensity (SI) of thrombi at 4 h was heterogeneously high or low on T2W or T1W images, respectively. The SI of thrombi on T2W images decreased time-dependently, but increased on T1W images at 1 and 2 weeks. Morphological analysis showed time-dependent decreases in erythrocyte, platelet and fibrin areas and time-dependent increases in smooth muscle cell, macrophage, collagen and iron areas. The t-PA administration significantly decreased thrombus volume at 4 h but not at 1, 2 and 4 weeks. Venous thrombosis can be reliably and noninvasively detected by MRI. Measurement of SI might support assessments of thrombus age and thrombolytic response.

We succeeded in synthesizing single crystals of a novel nickel sulfate Ni2-δSO5 by a hydrothermal method. A single-crystal X-ray diffraction revealed a tetragonal structure with lattice constants, a = 5.184 Å and c = 12.91 Å. In this structure, one-dimensional chains composed of face-shared NiO6 octahedra elongate along the a axis and the b axis alternately, constructing a ‘log-cabin’ type framework where neighbor chains lying orthogonally to each other are connected by SO4 tetrahedra. A detailed refinement of the structure suggested that the site occupancy of Ni is only 63%, corresponding to δ ≈ 2/3. Furthermore, X-ray oscillation photographs exhibit diffuse-scattering patterns probably arising from a short-range order of the Ni defects. Magnetic susceptibility revealed an antiferromagnetic transition accompanied by a weak ferromagnetism at 17 K.

SPIE Organic Photonics + Electronics, 2018, San Diego, California, United States, H. Yoshida, M. Takahashi, T. Ohkawa, J.-i. Fukuda, H. Kikuchi, and M. Ozaki "Three-dimensional crystal orientation of blue phase liquid crystals on surfaces", Proc. SPIE 10735, Liquid Crystals XXII, 107350I (14 September 2018). https://doi.org/10.1117/12.2323159, Liquid crystalline cholesteric blue phases (BPs) are of high interest for tunable electro-optic applications owing to their fast response times and quasi-polarization-independent phase modulation capabilities. Various approaches have recently been proposed to control the crystal orientation of BPs on substrates, but their basic orientation properties on standard, unidirectionally orienting substrates had not been investigated in detail. Here, detailed studies have been made on the Kossel diagrams of BPs on unidirectionally orienting substrates to understand the three-dimensional crystal orientation of BPs. We find that BPs show strong thermal hysteresis and that the structure of the preceding phase determines the orientation of BPs. Specifically, the BP II – I transition is accompanied by a rotation of the crystal such that the crystal direction defined by certain low-value Miller indices transform into different directions, and within the allowed rotations, different azimuthal configurations are obtained in the same cell depending on the thermal process. Our findings demonstrate that, for the alignment control of BPs, the thermal process is as important as the properties of the alignment layer.

Liquid crystalline cholesteric blue phases (BPs) continue to attract interest due to their fast response times and quasi-polarization-independent phase modulation capabilities. Various approaches have recently been proposed to control the crystal orientation of BPs on substrates; however, their basic orientation properties on standard, unidirectionally orienting alignment layers have not been investigated in detail. Through analysis of the azimuthal orientation of Kossel diagrams, we study the 3D crystal orientation of a BP material—with a phase sequence of cholesteric, BP I, and BP II—on unidirectionally orienting surfaces prepared using two methods: rubbing and photoalignment. BP II grown from the isotropic phase is sensitive to surface conditions, with different crystal planes orienting on the two substrates. On the other hand, strong thermal hysteresis is observed in BPs grown through a different liquid crystal phase, implying that the preceding structure determines the orientation. More specifically, the BP II–I transition is accompanied by a rotation of the crystal such that the crystal direction defined by certain low-value Miller indices transform into different directions, and within the allowed rotations, different azimuthal configurations are obtained in the same cell depending on the thermal process. Our findings demonstrate that, for the alignment control of BPs, the thermal process is as important as the properties of the alignment layer.

Rationale and Objectives Atherothrombosis usually occurs on macrophage- and lipid-rich unstable plaque, but rarely on smooth muscle cell (SMC)-rich stable plaque. Magnetic resonance imaging (MRI) has been extensively applied for noninvasive vascular imaging. We therefore investigated whether MRI provides valuable information about the characteristics of atherosclerotic vessels using rabbit models of macrophage-rich or SMC-rich atherosclerotic arteries. Materials and Methods Rabbits were fed with a conventional (CD group, n = 3) or 0.5% cholesterol (ChD group, n = 3) diet for 1 week before and 3 weeks after balloon injury of the left iliac arteries. Three weeks later, these arteries were investigates by 1.5 T MRI and by conventional angiographic imaging, followed by histological and immunohistochemical analyses. Results Three weeks after balloon injury, injured iliac arteries of both groups formed neointima with luminal stenosis. Conventional and MRI angiographic findings of the luminal diameter significantly and positively correlated. T1 relaxation time was significantly shorter and the lipid content was much higher in injured arteries from the ChD than from the CD group. The injured arteries from the ChD also contained more macrophages and less SMCs that those from the CD group. The T1 relaxation time and lipid content in injured arteries negatively and positively correlated with the degree of macrophage accumulation, respectively. Conclusion These results showed that MRI could provide valuable information about luminal stenosis and the characteristics of atherosclerotic vessels in rabbits.

Introduction Thrombus growth under low blood flow velocity plays an important role in the development of deep venous thrombosis (DVT). Increased plasma levels and activities of coagulation factor VIII (FVIII) comprise risk factors for DVT and pulmonary thromboembolism. Objective To localize FVIII in human venous thrombi of DVT and to determine whether FVIII contributes to thrombus formation under low shear conditions. Methods The localization of FVIII in venous thrombi obtained from patients with DVT was examined by immunohistochemistry. The role of FVIII in thrombus formation was investigated using a flow chamber system. Venous blood from healthy volunteers were incubated with an anti-FVIII monoclonal antibody (VIII-3776) or non-immunized mouse IgG1. Blood samples were perfused on immobilized type III collagen at wall shear rates of 70/s and 400/s and then the surface area covered by platelets and fibrin was morphometrically evaluated. Prothrombin fragment 1+2 (PF1+2) generation was measured before and after perfusion. Results Venous thrombi of DVT comprised a mixture of platelets, fibrin and erythrocytes. Factor VIII appeared to be colocalized with glycoprotein IIb/IIIa, fibrin and von Willebrand factor in the thrombi. VIII-3776 specifically recognized the light chain of FVIII and prolonged the activated partial thromboplastin time (aPTT), but not prothrombin time (PT). The antibody significantly reduced platelets and fibrin covering, as well as PF1+2 generation at wall shear rates of 70/s and 400/s. Conclusions These results suggest that FVIII contributes to platelet aggregation and fibrin formation via thrombin generation under low shear conditions.

Arterial thrombosis occurs in atherosclerotic, but rarely in non-atherosclerotic arteries. The present study investigates how hyperlipidemic condition affects thrombus formation on macrophage-rich neointima or normal intima in rabbits. Rabbits were fed with a 0.5% cholesterol diet, and then the femoral artery on one side of each rabbit was injured with a balloon catheter. Three weeks later, bilateral femoral arteries were similarly injured with a balloon catheter to produce thrombi on neointima and normal intima. We compared the expression and activity of intimal tissue factor (TF) as well as thrombus size and composition between these femoral arteries. 0.5% cholesterol diet combined with a balloon injury induced macrophage-rich neointima in injured arteries. The whole blood coagulation activity or plasma thrombin generation activity did not differ after consuming the 0.5% cholesterol diet for 4 weeks, and an anti-TF antibody did not affect the measured parameters. TF activities were increased in the neointima/media compared with normal intima/media. Balloon injury induced large platelet-fibrin thrombi on macrophage-rich neointima, whereas small platelet thrombi were produced in normal arteries even under hyperlipidemic conditions. Recombinant human tissue factor pathway inhibitor (25microg/(kgmin)) and argatroban (100microg/(kgmin)), a specific thrombin inhibitor, significantly reduced thrombus formation on induced neointima, but not on normal intima. Thrombin generation mediated by TF in intima contributes to thrombus formation on macrophage-rich neointima, but not on normal intima. The TF content in disrupted atherosclerotic plaques might play a more important role than hyperlipidemia in the development of atherothrombosis.

Plaque disruption with subsequent thrombus formation is a major cause of atherothrombotic diseases and von Willebrand factor (VWF), which is cleaved by ADAMTS-13, plays a critical role in thrombus formation. However, the role of ADAMTS-13 during thrombogenesis on atherosclerotic vessel remains unknown. We examined the localization of ADAMTS-13 in coronary thrombi obtained from patients with acute myocardial infarction. We also investigated the roles of ADAMTS-13 in thrombus formation using type I collagen-coated flow chambers (100S(-1) and 1500S(-1)) and on injured neointima of rabbit femoral arteries. ADAMTS-13 was present in thrombi of human coronary arteries, where it co-localized with VWF. In a flow chamber, both the average of the surface covered by platelet adhesion and the long axes of platelet thrombi were significantly augmented by an antibody to the ADAMTS-13 disintegrin-like domain (WH2-22-1A) at a shear rate of 1500s(-1), but not by an antibody to the ADAMTS-13 thrombospondin 1-3 domain (WH10). WH2-22-1A also reduced the activity of plasma ADAMTS-13 to cleave large VWF multimers during perfusion. Thrombi on injured neointima were induced by repeated balloon injury of rabbit femoral arteries, and were composed of platelet and fibrin, like human coronary thrombi. WH2-22-1A significantly augmented thrombus formation on injured neointima. These results suggest that the disintegrin-like domain of ADAMTS-13 functions in attenuating thrombus growth on diseased arteries exposed to a high shear rate.

Dengue fever (DF) is an infectious disease caused by the dengue virus (DENV). In addition to symptoms such as pyrexia, myalgia, arthralgia and eye pain, it presents with the characteristic skin finding of “white islands in a sea of red”. Serious cases include dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). We report a DHF patient with a Roth's spot.A 62-year-old man had returned from Thailand with fever (38 °C). He visited our department for systemic erythema developing 6 days [...]

A new chlorinated metabolite designated chlokamycin (1), was isolated along with ikarugamycin (2) from the culture broth of the marine-derived Streptomyces sp. MA2–12. The structure of 1 was elucidated based on spectroscopic analyses (1D and 2D NMR data and ROESY correlations). Chlokamycin moderately inhibited the growth of Jurkat cells and HCT116 cells with IC50 values of 24.7 and 33.5 μM, respectively.

Primary syphilis caused by Treponema pallidum usually develops after sexual contact as an initial solitary sclerosis or hard chancre in the genital region. We describe a case of primary syphilis at three sites in genital and extragenital regions of a man who had sex with men. A 29-year-old man visited our hospital for skin lesions on his lower lip, nipple-areola and penis. A positive syphilis serological test for rapid plasma reagin had a titer of 1:16; the patient also tested positive for specific antibodies against T. pallidum, with a cut-off index of 39.0. Histopathological examination of a nipple-areola biopsy specimen revealed a thickened epidermis and dense infiltration of inflammatory cells extending from the upper dermal layers to the deep dermis. The inflammatory cells were composed of abundant lymphocytes, plasma cells, histiocytes and neutrophils. Immunohistochemical staining for T. pallidum using an anti-T. pallidum antibody showed numerous spirochetes in the lower portion of the epidermis, scattered inside inflammatory cell infiltrate and perivascular sites throughout the dermis. Based on these findings, the patient was diagnosed with primary syphilis. Treatment with oral amoxicillin hydrate was started. Five days after starting treatment, a diffuse maculopapular rash (syphilitic roseola) occurred on his trunk and extremities. Perivascular cuffing due to T. pallidum was present throughout the dermis in the biopsy specimen of a localized lesion of primary syphilis. Moreover, syphilitic roseola, which indicates generalized dissemination of T. pallidum, developed during the course of treatment for primary syphilis. Therefore, we considered perivascular cuffing to be indicative of the dissemination phase.

Optical saturable absorption through monolayer graphene vertically inserted between fibers and overlaid on an ion-exchanged waveguide was measured for picosecond switching application. Modulation depth of absorption larger than 10dB was obtained in the latter structure.

High plasma levels of C-reactive protein (CRP) constitute a powerful predictive marker of cardiovascular events. Several lines of evidence suggest that CRP has prothrombogenic effects. However, whether CRP directly participates in the pathogenesis of thrombosis in vivo has not been fully clarified.To test whether human CRP (hCRP) affects arterial thrombus formation after balloon injury of smooth muscle cell (SMC)-rich or macrophage-rich neointima.We compared the susceptibility of transgenic (Tg) rabbits expressing hCRP (46.21 ± 13.85 mg L(-1), n = 22) and non-Tg rabbits to arterial thrombus formation after balloon injury of SMC-rich or macrophage-rich neointima.Thrombus size on SMC-rich or macrophage-rich neointima was significantly increased, and was accompanied by an increase in fibrin content in hCRP-Tg rabbits, as compared with non-Tg rabbits. Thrombus size did not significantly differ between SMC-rich and macrophage-rich neointima in hCRP-Tg rabbits. Tissue factor (TF) mRNA expression and activity in these neointimal lesions were significantly increased in hCRP-Tg rabbits as compared with non-Tg rabbits. The degree of CRP deposition correlated with the elevated TF expression and thrombus size on injured neointima. In addition, hCRP isolated from hCRP-Tg rabbit plasma induced TF mRNA expression and activity in rabbit cultured vascular SMCs.These results suggest that elevated plasma hCRP levels promote thrombus formation on injured SMC-rich neointima by enhancing TF expression, but have no additive effects in macrophage-rich neointima.

It has been generally considered that platelets are less important in venous thrombus formation. However, clinical studies have shown an association between venous thromboembolism (VTE) and von Willebrand factor (VWF). We therefore investigated the contribution of VWF and platelet interaction to the onset of VTE using tissues from autopsies and from an animal model. An immunohistochemical study revealed that glycoprotein (GP) IIb/IIIa, fibrin, glycophorin A (erythrocyte-specific protein) and VWF were consistently localized in ilio-femoral venous thrombi and in pulmonary thromboemboli from 8 autopsied cases who died of VTE, and VWF was closely associated with GPIIb/IIIa and fibrin. Venous thrombi and pulmonary emboli contained significant amounts of GPIIb/IIIa and VWF, in addition to glycophorin A and fibrin, and the factors did not significantly differ between them. A rabbit model of VTE was developed by inserting a polyethylene tube into the iliac vein. The constituents of the induced thrombi were quite similar to those of human VTE. An antibody against VWF (AJW200), which inhibits interactions between the VWF A1 domain and platelet GPIb, significantly reduced venous thrombus formation and pulmonary thromboembolism in the model. These results suggest that VWF A1-platelet GPIb interaction plays a significant role in venous thrombus formation.

Introduction In addition to acquired and inherited risk factors, the growth of venous thrombus under static conditions and endothelial injury play important roles in the development of deep venous thrombosis (DVT), for which risk factors include increased plasma levels of coagulation factor XI (FXI). The aim of this study is to understand the role of FXI in venous thrombus formation under conditions of endothelial denudation and/or blood stasis. Materials and methods The contribution of FXI to venous thrombus formation was investigated in a rabbit model and a flow chamber system. Thrombi were induced in the rabbit jugular veins by (1) endothelial denudation, (2) vessel ligation (blood stasis) or (3) by combined endothelial denudation and vessel ligation. Blood samples were perfused on immobilized type III collagen at a wall shear rate of 70/s and then the surface area covered by platelets and fibrin was morphometrically evaluated. Prothrombin fragment 1 + 2 (F1 + 2) generation was also measured before and after perfusion. Results All thrombi induced in rabbit jugular veins were composed of platelets, fibrin and erythrocytes. Anti-FXI antibody significantly reduced ex vivo plasma thrombin generation initiated by ellagic acid but not by tissue factor, and in vivo thrombus formation under endothelial denudation and/or vessel ligation. The antibody significantly reduced surface areas covered by platelets and fibrin, as well as F1 + 2 generation at a wall shear rate of 70/s in flow chambers. Conclusion These results suggest that FXI contributes to venous thrombus growth under conditions of endothelial denudation and/or blood stasis, and that thrombin generation by FXI interaction promotes further platelet aggregation and fibrin formation at low shear rates.