Tissue Vessels Research Articles

Hyperglycemia Induces Altered Expressions of Angiogenesis Associated Molecules in the Trophoblast

We previously reported that the increased level of perlecan with altered glycosaminoglycan (GAG) substitution was present in the placenta with gestational diabetes mellitus (GDM) and in the trophoblasts cultured under hyperglycemic condition. Trophoblast is the first cell lineage to differentiate, invasive, and migrate into the vessel tissues of placenta and fetal membrane during pregnancy. Therefore, active matrix remodeling and vessel formation must occur during placentation. In this study, we further investigated whether hyperglycemia-induced alterations of perlecan in the extracellular matrix (ECM) affect the proliferation and the expressions of angiogenesis-related growth factors and cytokines in the trophoblasts. 3A-Sub-E trophoblastic cells cultured in high glucose medium were conducted to mimic the hyperglycemic condition. Results showed that the hyperglycemia-induced GAG alterations in the cell surface perlecan as well as in the ECM indeed upregulated the expressions of IL-6, IL-8, and MCP-1 and the activities of MMP-2 and MMP-9 and downregulated the expressions of TIMP-2. A regulatory molecular mechanism of hyperglycemia-induced alterations of the cell surface proteoglycans and the ECM remodeling on the expressions of angiogenesis-related cytokines and growth factors in trophoblasts was proposed. This mechanism may contribute to the aberrant placental structure and the maternal and fetal complications during development.

Commentary on the paper “Cervicothoracic reconstruction with an anteromedial thigh flap: A novel flap concept”

This is a commentary on the paper “Cervicothoracic reconstruction with an anteromedial thigh flap: a novel flap concept”. It is an excellent case. The method to use a segment of SFA to replace the carotid artery is great and the defect of SFA could be reconstructed with a Gore-Tex prosthesis. This method has the following advantages: (1) When the cancer has invaded the carotid artery with encasement, this method provides a more radical way of ablating the malignancy. (2) In the presence of potential infection, this method provides an autogenous tissue graft for the carotid artery instead of an artificial graft which has more chance of infection and blow-out. (3) In addition to a segment of SFA, it carries soft tissue and skin for simultaneous reconstruction of defects of large vessel and soft tissue. However, the author should be careful about the anatomical variations of perforators at the medial thigh region. Secondly, the territory of the skin paddle is still not clearly defined with individual difference, so that partial loss can happen if the skin paddle is too large. Even CT angiography has proved the presence of perforators, the area of complete survival for medial thigh flap is not so clear as the anterolateral thigh flap. The venous return of the flap should also be watched for a large anteromedial thigh flap. I would suggest using a smaller anteromedial

Serum Sickness After Antithymocyte Globulin Administration in a Cardiac Transplant Patient

Serum Sickness After Antithymocyte Globulin Administration in a Cardiac Transplant Patient

Lotus-leaf-like structured heparin-conjugated poly(L-lactide-co-ɛ-caprolactone) as a blood compatible material

A heparin-conjugated biodegradable polymer was synthesized by direct coupling of heparin to poly(L-lactide-co-ɛ-caprolactone) (PLCL) and was manufactured into lotus-leaf-like structured films. We evaluated whether lotus-leaf-like structured heparin-conjugated PLCL (LH-PLCL) could be applied to blood vessel tissue engineering. Differences in the surface structures of the films with respect to hydrophobicity and the lotus effect as well as the antithrombotic efficiency in human whole blood were examined using scanning electron microscopy (SEM) and a contact angle meter. Recovery testing was conducted using a tensile strength testing machine, and quantitative analysis of conjugated heparin was performed using the toluidine blue colorimetric method. The concentration of conjugated heparin was 0.14μg/mg H-PLCL, and the contact angle with the lotus-leaf-like surface was approximately 120°. Furthermore, the LH-PLCL film yielded a lower platelet adhesion rate (around less than 1.4%) in whole blood than that yielded by an untreated PLCL film. These results indicate a unique property of bound heparin and the lotus-leaf-like structure. This novel LH-PLCL polymer could be applied as a blood/tissue compatible biodegradable material for implantable medical devices and tissue engineering.

Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half LIM domains 5 plays a key role for vein graft intimal hyperplasia

Intimal hyperplasia (IH) is the main cause of vein graft stenosis or failure after bypass surgery. Basic investigations are proceeding in an animal model of mechanically desquamated arteries, and numerous molecules for potential IH treatments have been identified; however, neither insights into the mechanism of IH nor substantially effective treatments for its suppression have been developed. The goals of the present study are to use human vein graft samples to identify therapeutic target genes that control IH and to investigate the therapeutic efficacy of these candidate molecules in animal models. Using microarray analysis of human vein graft samples, we identified two previously unrecognized IH-related genes, mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) and four-and-a-half LIM domains 5 (FHL5). Transfer of either candidate gene resulted in significantly elevated vascular smooth muscle cell (VSMC) proliferation and migration. Interestingly, cotransfection of both genes increased VSMC proliferation in an additive manner. These genes activated cyclic adenosine monophosphate response-element (CRE) binding protein (CREB), but their mechanisms of activation were different. MAPKAPK3 phosphorylated CREB, but FHL5 bound directly to CREB. A CREB dominant-negative protein, KCREB, which blocks its ability to bind CRE, repressed VSMC proliferation and migration. In a wire-injury mouse model, gene transfer of KCREB plasmid significantly repressed IH. In this vessel tissue, CRE-activated gene expression was repressed. Furthermore, we confirmed the changes in MAPKAPK3 and FHL5 expression using vein graft samples from eight patients. We successively identified two previously unrecognized IH activators, MAPKAPK3 and FHL5, using human vein graft samples. Gene transfer of KCREB repressed IH in an animal model. Inhibition of CREB function is a promising gene therapy strategy for IH.

Selection of Polyhydroxybutyrate-Co-Valerate (PHBV) as An Improved Polymer Choice in FTY720 Loaded Nanofibers for Islet Transplant

Introduction: These studies aim to determine a biodegradeable polymer that can be used within a tissue engineering device that does not reduce the viability of islets to the same degree as poly(lactic-co-glycolic acid) (PLAGA), but can still be successfully electrospun and loaded with FTY720. Drug release profile and in vivo immune response support the new polymer choice. Methods: Nanofibers are electrospun resulting in scaffolds consisting of several types of polymers, including equal blends by weight with polycaprolactone (PCL), with and without FTY720. Images are obtained from dorsal skinfold window chambers where a FTY720 loaded implant and an unloaded implant are placed in the same animal immediately following window surgery. Microvessel metrics are quantified with a MATLAB program. Islets are stained for viability (Propidium Iodide and Fluorescein Diacetate). Release samples are analyzed with Liquid Chromatography-Mass Spectrometry (LC-MS) following lipid extraction. Hematoxylin and Eosin stained slides are obtained from paraffin embedded tissue samples. Results: Human islets tested with PLAGA/PCL nanofibers displayed a decrease in viability compared to the media only controls (68% PLAGA/PCL verses 78% media only). Other polymer types polyhydroxybutyrate (PHB) and polyhydroxybutyrate-co-valerate (PHBV) performed better in this assay (75% and 79% respectively). LC-MS assisted in vitro release data indicate that a burst release (>10% loaded drug within 48 hours) is followed by a steady release resulting in 25% of the loaded FTY720 released by 2 weeks. Water droplet absorption time into nanofiber scaffolds indicate differences when FTY720 is added (< 5 sec FTY720 Loaded verses >3 min Unloaded scaffold, until complete wetting) likely related to the amphiphilic character of FTY720. Image analysis of window chambers with dual implants, indicate that after an initial 3 day time period a preferential blood flow in the area surrounding the FTY720 loaded implant exists as measured by both volume of blood in the tissue and length of visible blood vessels. Preliminary histology from subcutaneous implant studies indicate that the PLAGA/PCL fiber scaffolds contain more inflammatory cells and are characterized by tertiary lymphoid tissue development. In contrast, the PHBV/PCL fibers elicit an immune response, but do not result in formation of lymphoid tissue. Conclusion: The monomers of PLAGA are acidic. A decrease in culture media pH may contribute to a loss in islet viability with PLAGA fibers, which is less of an issue with the slower degrading PHBV. FTY720 releases from the fibers at a rate which can drive microvessel remodeling following injury perhaps by the recruitment of microvessel support cells. A depot of FTY720 is maintained however that will release for an extended period of time. Water droplet absorption combined with the burst release suggest that some of the FTY720 is locating near the surface of the fibers. PHBV scaffolds improved viability of islets in culture over PLAGA/PCL scaffolds. Preliminary in vivo studies demonstrate that PHBV/PCL fibers instigate less of an immune response than PLAGA/PCL fibers. In conclusion, PHBV has shown promise as a replacement polymer for PLAGA in FTY720 loaded nanofiber scaffolds for islet transplant.

Electrospinning collagen/chitosan/poly(L‐lactic acid‐co‐ϵ‐caprolactone) to form a vascular graft: Mechanical and biological characterization

For blood vessel tissue engineering, an ideal vascular graft should possess excellent biocompatibility and mechanical properties. For this study, a elastic material of poly (L-lactic acid-co-ε-caprolactone) (P(LLA-CL)), collagen and chitosan blended scaffold at different ratios were fabricated by electrospinning. Upon fabrication, the scaffolds were evaluated to determine the tensile strength, burst pressure, and dynamic compliance. In addition, the contact angle and endothelial cell proliferation on the scaffolds were evaluated to demonstrate the structures potential to serve as a vascular prosthetic capable of in situ regeneration. The collagen/chitosan/P(LLA-CL) scaffold with the ratio of 20:5:75 reached the highest tensile strength with the value of 16.9 MPa, and it was elastic with strain at break values of ~112%, elastic modulus of 10.3 MPa. The burst pressure strength of the scaffold was greater than 3365 mmHg and compliance value was 0.7%/100 mmHg. Endothelial cells proliferation was significantly increased on the blended scaffolds versus the P(LLA-CL). Meanwhile, the endothelial cells were more adherent based on the increase in the degree of cell spreading on the surface of collagen/chitosan/P(LLA-CL) scaffolds. Such blended scaffold especially with the ratio of 20:5:75 thus has the potential for vascular graft applications.

RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response

Recognition of virus infection by innate pattern recognition receptors (PRRs), including membrane-associated toll-like receptors (TLR) and cytoplasmic RIG-I-like receptors (RLR), activates cascades of signal transduction pathways leading to production of type I interferons (IFN) and proinflammatory cytokines that orchestrate the elimination of the viruses. Although it has been demonstrated that PRR-mediated innate immunity plays an essential role in defending virus from infection, it also occasionally results in overwhelming production of proinflammatory cytokines that cause severe inflammation, blood vessel leakage and tissue damage. In our efforts to identify small molecules that selectively enhance PRR-mediated antiviral, but not the detrimental inflammatory response, we discovered a compound, RO 90–7501 (‘2’-(4-Aminophenyl)-[2,5′-bi-1H-benzimidazol]-5-amine), that significantly promoted both TLR3 and RLR ligand-induced IFN-β gene expression and antiviral response, most likely via selective activation of p38 mitogen-activated protein kinase (MAPK) pathway. Our results thus imply that pharmacological modulation of PRR signal transduction pathways in favor of the induction of a beneficial antiviral response can be a novel therapeutic strategy.

CHRONIC INTERMITTENT HYPOXIA INDUCES HIGH BLOOD PRESSURE AND OXIDATIVE STRESS IN RATS

ObjectivesChronic intermittent hypoxia (CIH) is a typical feature of obstructive sleep apnoea (OSA) and is associated with oxidative stress and systemic endothelial dysfunction, which leads to systemic hypertension and other...

Florid Arteritis Confined to a Single Branch of the Superficial Temporal Artery

for the integrity of the data and the accuracy of the data analysis. Financial Disclosure: None reported. Funding/Support: This work was supported by Eye Tu- mor Research Foundation, Philadelphia, Pennsylvania (Drs J. A. Shields and C. L. Shields). Role of the Sponsor: The sponsor had no role in the de- sign and conduct of the study; in the collection, analy- sis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. 1. Zimmerman LE, Garron LK. Melanocytoma of the optic disc. Int Ophthalmol Clin. 1962;2:431-440. 2. Apple DJ, Craythorn JM, Reidy JJ, Steinmetz RL, Brady SE, Bohart WA. Ma- lignant transformation of an optic nerve melanocytoma. Can J Ophthalmol. 3. Shields JA, Shields CL, Eagle RC Jr, Lieb WE, Stern S. Malignant melanoma associated with melanocytoma of the optic disc. Ophthalmology. 1990;97 4. Meyer D, Ge J, Blinder KJ, Sinard J, Xu S. Malignant transformation of an op- tic disk melanocytoma. Am J Ophthalmol. 1999;127(6):710-714. 5. Shields JA, Demirci H, Mashayekhi A, Shields CL. Melanocytoma of optic disc in 115 cases: the 2004 Samuel Johnson Memorial Lecture, part 1. Ophthalmology. 6. Shields JA, Demirci H, Mashayekhi A, Eagle RC Jr, Shields CL. Melanocy- toma of the optic disk: a review. Surv Ophthalmol. 2006;51(2):93-104. 7. Horgan N, Shields CL, Swanson L, et al. Altered chromosome expression of uveal melanoma in the setting of melanocytosis. Acta Ophthalmol. 2009;87 branches of the superficial temporal artery. In fact, sur- geons usually fail to specify which branch was biopsied when they submit specimens, and no histological data exist regarding which branch is more likely to demon- strate arteritis. Recently, it was suggested that the parietal branch, rather than the frontal branch, should be biopsied in pa- tients with suspected temporal arteritis. 3 This approach eliminates the remote risk of facial nerve injury and usu- ally hides the scar behind the hairline. However, this rec- ommendation was predicated on the assumption that the prevalence of arteritis is equal in the parietal and frontal branches. We now show that selective involvement of a single vessel branch can occur in temporal arteritis. Magnetic resonance imaging has been used to com- pare the involvement of the parietal vs frontal branch in temporal arteritis. In 21 patients with suspected giant cell arteritis, involvement was rated by noting the amount of mural thickening and gadolinium enhancement of the vessel and perivascular tissue. 4 On the left side, abnor- malities were present in 14 patients in the frontal branch and in 6 patients in the parietal branch. On the right side, A Florid Arteritis Confined to a Single Branch of the Superficial Temporal Artery B iopsy of the superficial temporal artery provides vital confirmation of the diagnosis of giant cell arteritis. The vessel splits into 2 main branches: frontal and parietal. It is unknown which branch is most likely to yield a positive biopsy finding or, indeed, whether arteritis is ever confined to a single branch. Report of a Case. A 69-year-old woman had a 5-week history of neck stiffness and malaise. The erythrocyte sedi- mentation rate was 55 mm/h. A 30-mm segment of the parietal branch of the left superficial temporal artery was harvested. It was processed with hematoxylin-eosin stain and an elastic Van Gieson stain. A total of 108 sections were examined at 36 different levels. None showed evi- dence of arteritis ( Figure 1 ). Two days later, a 30-mm section of the frontal branch of the left superficial tem- poral artery was biopsied. Every section showed exten- sive granulomatous inflammation ( Figure 2 ). The pa- tient was treated with prednisone and her symptoms resolved. Comment. It is crucial to obtain a biopsy specimen of adequate length to avoid the problem of “skip areas” in the superficial temporal artery. It is also important to ex- amine the specimen thoroughly by reviewing sections cut at many levels because inflammation can be confined to just a few portions of the artery. Otherwise, there is risk of a false-negative biopsy result. 1,2 We describe an ex- treme example of a skip area: a parietal branch com- pletely free of inflammation in a patient with extensive arteritis of the frontal branch. To our knowledge, no prior report has compared pathological findings in the 2 B Figure 1. Patient showing biopsy sites from the parietal and frontal branches of the left superficial temporal artery (A), and representative sections, spaced evenly from 9 different levels of the parietal branch of the left superficial temporal artery, showing no evidence of arteritis (hematoxylin-eosin, original magnification ⫻12) (B). ARCH OPHTHALMOL / VOL 130 (NO. 10), OCT 2012 WWW.ARCHOPHTHALMOL.COM ©2012 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by a UCSF LIBRARY User on 08/10/2015

Rapidly-moving insect muscle-powered microrobot and its chemical acceleration

Insect dorsal vessel (DV) tissue seems well suited for microactuators due to its environmental robustness and low maintenance. We describe an insect muscle-powered autonomous microrobot (iPAM) and its acceleration with a neuroactive chemical, crustacean cardioactive peptide (CCAP). The iPAM, consisting of a DV tissue and a frame, was designed on the basis of a finite element method simulation and fabricated. The iPAM moved autonomously by spontaneous contraction of the DV tissue at a significantly improved velocity compared to our previous model. The best-case iPAM moved faster than other reported microrobots powered by mammalian cardiomycytes. It moved forward with a small declination of 0.54 ° during one contraction since the DV tissue not only shortened but also twisted. The iPAM frame should be designed by taking into account the innate contractile characteristic of DV tissue. The acceleration effect of CCAP on contracting frequency was evaluated using a micropillar array and was a maximum at 10(-6)M. The effect peaked 1 min after addition and remained for 2 min. CCAP addition at 10(-6)M accelerated the iPAM temporally and the velocity increased 8.1-fold. We view the DV tissue as one of the most promising materials for chemically regulatable microactuators.

Identification, spatial expression analysis and functional characterization of a pyrokinin-1 receptor in the Chagas’ disease vector, Rhodnius prolixus

The capability or capa gene, encodes a pyrokinin-related peptide (known as pyrokinin-1, PK1) that contains the consensus carboxy-terminal sequence of WFGPRL–NH2. Although the CAPA precursor polypeptide in Rhodnius prolixus yields the anti-diuretic hormone, RhoprCAPA-α2, no function has yet been elucidated for the pyrokinin-1 peptide, RhoprCAPA-αPK1. In order to elucidate the possible physiological roles of the PK1-related peptides in R. prolixus, we have isolated and functionally characterized the PK1 receptor, RhoprPK1-R. Additionally, we have determined a set of three optimal reference genes to utilize for normalization of data obtained when carrying out spatial expression analyses via quantitative reverse transcriptase PCR (RT-qPCR) in various tissues of fifth instar R. prolixus. The RhoprPK1-R expression profile differs strikingly from the receptor for the anti-diuretic hormone RhoprCAPA-α2, which is localized mainly to gut epithelial tissues. Instead, RhoprPK1-R expression in fifth instar stage insects was identified in tissues that are not involved in osmotic and ionic balance, including the prothoracic glands, male reproductive tissues and a pooled sample composed of fat body, dorsal vessel, abdominal nerves and female reproductive tissues. Thus, this research establishes novel possibilities for the physiological roles of the pyrokinin-related peptides in this medically relevant disease vector.

Development and evaluation of axially aligned nanofibres for blood vessel tissue engineering

Biodegradable polymers have been extensively used as scaffolds to regenerate lost tissues. The geometry of the three-dimensional (3D) scaffolds has an influence on the cellular behaviour. In this study, we have developed 3D-scaffolds of axially aligned nanofibres of poly(lactic acid) (PLA), poly(caprolactone) (PCL) and PLA:CL (50:50) with diameters in the range 100-400 nm, internal diameter 4 mm, length 4 cm and wall thickness 0.2 mm, by using a dynamic collector. PCL and PLA:CL nanofibres were significantly less hydrophobic than PLA nanofibres. The porosity of PCL (16.23 ± 9.88%) and PLA:CL nanofibres (14.77 ± 3.41%) were comparable, while PLA (6.57 ± 1.54%) nanofibres had lower porosity. The tensile strength and Young's modulus of PLA was significantly lower than PCL and PLA:CL nanofibres and the suture retention strengths of all three scaffolds were comparable. After 4 weeks, the molecular weight of PLA nanofibres was reduced by 53% compared to 44% and 41% for PCL and the PLA:CL nanofibres, respectively. However, the PLA:CL nanofibres maintained their structural integrity even after 28 days. Platelet adhesion studies showed that PCL nanofibres had least tendency to be thrombogenic, while PLA:CL blend nanofibres were highly thrombogenic. Further, in vitro responses such as cell adhesion, proliferation and gene expression of human umbilical vascular endothelial cells (HUVECs) were evaluated. After 6 days of culture, the surfaces of all the three scaffolds were completely covered with cells. Our results demonstrate that expression levels of elastin, angiopoietin, laminin-4α and -5α were upregulated in PCL and PLA:CL nanofibres without the addition of any exogenous factors.

Effects of Chinese herbal medicine Neiyi Recipe-medicated serum on angiopoiesis of endometriosis in the chick chorioallantoic membrane model

To compare angiopoiesis ability of eutopic and ectopic endometrial tissue isolated from women with endometriosis and endometrium isolated from women without endometriosis (control), and to explore the inhibitory effects of medicated serum of Neiyi Recipe, a compound traditional Chinese herbal medicine. Chick chorioallantoic membrane (CAM) model of endometriosis was established by transplanting endometrium onto CAM. The CAMs were then hatched with blank serum or medicated serum of danazol or Neiyi Recipe, which were prepared in rats by orally administering. The sizes of the transplanted tissue and new vessels around the transplanted tissue were measured. Expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemical method. There was no difference in the sizes of transplanted tissue among CAM models of ectopic and eutopic endometrial tissue isolated from women with endometriosis or control (P>0.05), and more new vessels were found around the ectopic and eutopic endometrial tissue than the endometrial tissue of control (P<0.05). Compared with the controls, the size of the transplanted tissue and positive area of new vessels were significantly inhibited by Neiyi Recipe-medicated serum (P<0.01, P<0.05), and similar changes happened in the danazol groups, except for the size of transplanted tissue from ectopic endometrial tissue (P>0.05). Expression of VEGF was significantly higher in eutopic and ectopic endometrial tissue than in the control (P<0.01); the level of VEGF obviously reduced in the Neiyi Recipe and danazol groups (P<0.01), but no significant difference was detected between them. Endometrium from women with endometriosis stimulates the formation of new vessels by increase the expression of VEGF. Neiyi Recipe-medicated serum significantly decreases the expression of VEGF in eutopic and ectopic endometrial tissues and thus restrains the formation of new vessels, reduces the blood supply and inhibits growth of ectopic endometrial tissue, which are similar to danazol, but has greater efficacy in suppressing the expression of VEGF.

Room Temperature Operable Autonomously Moving Bio-Microrobot Powered by Insect Dorsal Vessel Tissue

Living muscle tissues and cells have been attracting attention as potential actuator candidates. In particular, insect dorsal vessel tissue (DVT) seems to be well suited for a bio-actuator since it is capable of contracting autonomously and the tissue itself and its cells are more environmentally robust under culturing conditions compared with mammalian tissues and cells. Here we demonstrate an autonomously moving polypod microrobot (PMR) powered by DVT excised from an inchworm. We fabricated a prototype of the PMR by assembling a whole DVT onto an inverted two-row micropillar array. The prototype moved autonomously at a velocity of 3.5×10−2 µm/s, and the contracting force of the whole DVT was calculated as 20 µN. Based on the results obtained by the prototype, we then designed and fabricated an actual PMR. We were able to increase the velocity significantly for the actual PMR which could move autonomously at a velocity of 3.5 µm/s. These results indicate that insect DVT has sufficient potential as the driving force for a bio-microrobot that can be utilized in microspaces.

Histologic identification of brown adipose and peripheral nerve involvement in human atherosclerotic vessels

The disease mechanisms and histology of plaque development associated with atherosclerosis remain incredibly complex and not entirely understood. Recent investigations have emphasized the importance of inflammation in atherosclerosis. Several studies have also indicated heterotopic or extraskeletal bone formation in atherosclerotic vessels. The mechanisms behind heterotopic ossification appear to have similarities to those underlying atherosclerosis, with inflammation being a key inductive component to heterotopic ossification. Therefore, in the present study, we evaluated the histology associated with pathologies of atherosclerosis and heterotopic ossification in 271 coronary vessel tissue samples. We examined the prevalence and features of the inflammatory response as well as new vessel and bone formation. Inflammation and neovascularization were observed both in the adventitia and within the atherosclerotic lesions of the vessels themselves. Intriguingly, neural changes, including collections of inflammatory cells and expression of neuroinflammatory factors, were detected in the adventitial nerves of the vessels. Mature lamellar bone was found in 18 coronary vessels (7%), often with hematopoietic elements and active bone remodeling. Brown adipocytes, which pattern heterotopic bone formation, were present within the atherosclerotic lesions (28%, or 75/271). As expected, there was a strong correlation between the presence of cholesterol and plaque formation (P < .0001), but there also seemed to be a trend toward a connection between the presence of brown adipocytes and plaque. From this histologic evaluation, along with cholesterol and dystrophic calcification, we noted a novel appearance of brown adipocytes as well as neural changes, which may provide new insights to further our understanding of atherosclerosis.

SU-E-J-191: A Multivariate Framework for N-Tissue Classification in Treatment Assessment of Glioblastomas.

Glioblastoma is the most common primary brain tumor in adults and is rapidly fatal. Treatment monitoring of these patients has increased awareness that many patients have new areas of contrast enhancement without progressive clinical signs and symptoms. Although the enhancing areas mimic tumor progression, the lesions result from treatment effects and subsequently stabilize or improve without further treatment and are not correlated with poorer outcomes. This phenomenon has been termed pseudoprogression and is hypothesized to occur secondarily to edema and vessel permeability in the tumor area as a result of the combined effects of radiation and chemotherapy. Since the new enhancing lesions of pseudoprogression are indistinguishable from true disease progression, there is a need for a predictive model to distinguish the two phenomena. We developed a classification algorithm that combines perfusion and diffusion MRI imaging to effectively partition the cases as one exhibiting true or pseudo progression based on a vector of features containing T1, rCBV and ADC imaging. The multi-sequence classification algorithm uses an expectation maximization (EM) algorithm that learns from training cases with known clinical outcome to assigns each voxel to a type of tissue. A training set of 20 where the clinical outcome is known from biopsy or from long-term follow-up was used by EM algorithm to model typical imaging values within tissue of pseudo, tumor, edema, necrosis, vessels or brain anatomy to construct a database of expected values for each tissue type. When presented with a new case, the algorithm automatically classifies voxels by their geographical proximities and Mahalanobis distance to the pre-sampled values. Usage of advanced classification techniques allows automated labeling of voxels into normal, pseudoprogression or tumoral tissue types. The technique allows for early detection of pseudo progression to spare patients from unnecessary surgery or toxic chemotherapy.

Patient-Specific Prediction of Coronary Plaque Growth From CTA Angiography: A Multiscale Model for Plaque Formation and Progression

Computational fluid dynamics methods based on in vivo 3-D vessel reconstructions have recently been identified the influence of wall shear stress on endothelial cells as well as on vascular smooth muscle cells, resulting in different events such as flow mediated vasodilatation, atherosclerosis, and vascular remodeling. Development of image-based modeling technologies for simulating patient-specific local blood flows is introducing a novel approach to risk prediction for coronary plaque growth and progression. In this study, we developed 3-D model of plaque formation and progression that was tested in a set of patients who underwent coronary computed tomography angiography (CTA) for anginal symptoms. The 3-D blood flow is described by the Navier-Stokes equations, together with the continuity equation. Mass transfer within the blood lumen and through the arterial wall is coupled with the blood flow and is modeled by a convection-diffusion equation. The low density lipoprotein (LDL) transports in lumen of the vessel and through the vessel tissue (which has a mass consumption term) are coupled by Kedem-Katchalsky equations. The inflammatory process is modeled using three additional reaction-diffusion partial differential equations. A full 3-D model was created. It includes blood flow and LDL concentration, as well as plaque formation and progression. Furthermore, features potentially affecting plaque growth, such as patient risk score, circulating biomarkers, localization and composition of the initial plaque, and coronary vasodilating capability were also investigated. The proof of concept of the model effectiveness was assessed by repetition of CTA, six months after.

Clinicopathological features of lymph node metastatic EMPNST: a case report and review of literatures

Background Mesenchymal malignancies prefer hematogenous spread, while epithelial malignancies tend to prefer lymphatic spread. However, mesenchymal malignancies occasionally generate lymphatic metastases. Objective To investigate the clinicopathological features of the epithelioid malignant peripheral nerve sheath tumor (EMPNST). Methods The clinical data, histopathological, histochemical and immunohistochemical features in one case of EMPNST with lymph node metastases were retrospectively analyzed, and the related literatures were reviewed. Results A 42 ⁃ year ⁃ old woman presented right upper arm and shoulder numbness with a right axillary nodule measuring 4 cm × 4 cm × 3 cm for 2 months. Type⁃B ultrasonic examination showed substantive lesions in right axillary which appeared to be a neurofibroma. CT scan showed soft tissue masses in right axillary with multiple enlarged lymph nodes were considered to be malignant lesions. MR image showed nodules in right armpit muscles were considered to be malignant tumor. The multiple nodules were identified in right axillary and the largest one was about 5 cm × 3 cm × 3 cm intraoperatively. The section of specimen was hard, gray⁃red and sallow in color with focal necrosis. The nodules were partly circumvoluted with blood vessel and without distinct border. The surrounding nerves were not obviously compressed. Microscopically, the structure of lymph node was damaged. The tumor invaded the surrounding fibrous connective tissue and adipose tissue with focal hemorrhage and necrosis. Tumor cells arranged in sheets, nests, and were separated by thin fibrous and blood vessels tissue. Most tumor cells were epithelioid. They were large in size with abundant cytoplasm. Cell border was indistinct, and the cytoplasm consisted of fine granules. Nuclei were invariably intensely hyperchromatic with coarse chromatin, and were vacuolated with prominent nucleoli in the center of the nuclei. Tumor cells showed frequent mitotic activity. Multinucleated giant cells and interstitial mucous degeneration were presented. Immunohistochemical staining showed that tumor cells were positive for S⁃100 protein, strong nuclear reactivity for Sox⁃10, and were positive for vimentin and Col⁃Ⅳ, and were negative for CK, CEA, EMA, Melan⁃A, CD56, CD3 and CD20. P53 positive revealed by 40% nuclear of tumor cells. Ki⁃67 labeling index was above 90%. Histochemical staining showed that the tumor cells were surrounded by reticular fibers. The patient had a medical history which recorded a tumor at the right wrist was removed in other hospital 8 years ago, and the wrist tumor recurred 5 years ago. The pathological diagnosis of the recurred wrist tumor was EMPNST with focal hemorrhage and necrosis. According to the history and the final pathological diagnosis, axillary tumor was diagnosed as lymph node metastasis of EMPNST in right axillary. Conclusion The metastasis of MPNST is mostly through the blood channel. This is the first case of the lymph node metastasis of EMPNST. In clinical work, it should be differentiated from other tumors with similar histopathology. DOI：10.3969/j.issn.1672⁃6731.2012.02.017

Pathology of the Fetal Neck

ABSTRACT Fetal neck is the site of important pathological changes, related to genetic, cardiovascular, lymphatic, endocrine systems. Among the main neck pathology are fetal hygroma, goiter, teratoma/sarcoma, hemangioma/lymphangioma. Posterior anomalies of the fetal neural tube, such as occipital myelomeningocele or iniencephaly may also be included in this area. Fetal hygroma is the main pathology, probably related to abnormal development of the lymphatic drainage system. There is a large spectrum of the disease, from enlarged nuchal translucency to generalized edema. Enlarged nuchal translucency is often associated with aneuploidy, particularly trisomy 21 and Turner syndrome (monosomy X). However, the pathophysiology is different for the two aneuploidies. On the diagnostic side, cystic hygromas consist of large single or multilocular fluid-filled cavities, which are usually easily identified during first trimester ultrasound examination. About one-third of euploid fetuses with first trimester septated cystic hygromas have major structural anomalies. In contrast, structural anomalies are detected in only 4 to 10% of euploid fetuses with enlarged nuchal translucency. Enlargement of fetal thyroid gland is accompanied by increased or decreased level of thyroid hormones (hyper or hypothyroidism), but the thyroid function may also be normal. The physiopathology of fetal and neonatal goiter is complex. Causes of fetal goiter include inborn errors of thyroid hormone production, transplacental passage of maternal antibodies, maternal ingestion of antithyroid drugs and other goitrogens, thyroid tumors. Detection of the fetal goiter is facilitated by the associated maternal history, present in most of the cases. By definition, goiter means enlargement of the thyroid gland above the 95th centile of the normal range. Reliable and objective data about fetal thyroid function involves an invasive testing. Teratomas are large mixed tumors arising from the neck region. Teratomas are cystic, semicystic or solid tumors. They develop from all three germ cell layers. Cervical teratomas are detected antenatally in most cases, as they are large size tumors. Hemangiomas and lymphangiomas are tumors derived from the endothelial tissue of blood vessels or lymphatic vessels. They may develop anywhere in the body, but in the antenatal life and the first years they show a predisposition for the head, neck and axillar area. Regarding the occipital encephalocele and iniencephaly, even though they represent major anomalies that affect he cervical and cephalic area, from a developmental point of view they are part of the neural tube defects spectrum and should be considered as such especially from a prognosis point of view. How to cite this article Vladareanu R, Zvanca M, Andrei C. Pathology of the Fetal Neck. Donald School J Ultrasound Obstet Gynecol 2012;6(1):55-65.