Lacunar Spaces Research Articles

A Novel Treatment for Cervical and Cesarean Section Scar Pregnancies by Transvaginal Injection of Absolute Ethanol to Trophoblasts: Efficacy in 19 Cases

Study ObjectiveTo evaluate the efficacy of a nonsurgical treatment for cervical pregnancy (CP) and cesarean section scar pregnancy (CSP). DesignRetrospective clinical study (Canadian Task Force classification III). SettingPrivate assisted reproductive technology practice. PatientsNineteen women with CP (n = 16) or CSP (n = 3), including 6 patients with positive fetal heartbeat. InterventionTransvaginal local injection of absolute ethanol (AE) into the hyperechoic ring (lacunar space) around the gestational sac under ultrasound guidance. Measurements and Main ResultsSerum beta-human chorionic gonadotropin (β-hCG) was measured at frequent intervals, and ultrasound and/or magnetic resonance imaging was used to observe the gestational sac. In 9 patients, the serum β-hCG level was effectively reduced with a single AE injection at 2 hours. In the remaining 10 patients, the level decreased but then increased in 4 and slowly decreased in the other 6; all of these 10 patients required 2 to 5 repeat AE injections. In all patients, serum β-hCG level was reduced by 50% within 3 days and decreased to <10% of the initial level within 14 days. In 18 patients (95%), the level was decreased to 1.0 mIU/mL within 40 days. Seven patients were treated on an outpatient basis. Twelve patients received no anesthesia. Five patients subsequently became pregnant, and each had a live birth. There was no recurrent CP or CSP. The procedure was successful in all 19 patients. ConclusionThis procedure is an effective treatment for CP or CSP that could be used in place of conventional surgical interventions and medical treatment using MTX.

The clustering and morphology of chondrocytes in normal and mildly degenerate human femoral head cartilage studied by confocal laser scanning microscopy.

Chondrocytes are the major cell type present in hyaline cartilage and they play a crucial role in maintaining the mechanical resilience of the tissue through a balance of the synthesis and breakdown of extracellular matrix macromolecules. Histological assessment of cartilage suggests that articular chondrocytes insitu typically occur singly and demonstrate a rounded/elliptical morphology. However, there are suggestions that their grouping and fine shape is more complex and that these change with cartilage degeneration as occurs in osteoarthritis. In the present study we have used confocal laser scanning microscopy and fluorescently labelled insitu human chondrocytes and advanced imaging software to visualise chondrocyte clustering and detailed morphology within grade-0 (non-degenerate) and grade-1 (mildly degenerate) cartilage from human femoral heads. Graded human cartilage explants were incubated with 5-chloromethylfluorescein diacetate and propidium iodide to identify the morphology and viability, respectively, of insitu chondrocytes within superficial, mid- and deep zones. In grade-0 cartilage, the analysis of confocal microscope images showed that although the majority of chondrocytes were single and morphologically normal, clusters (i.e. three or more chondrocytes within the enclosed lacunar space) were occasionally observed in the superficial zone, and 15-25% of the cell population exhibited at least one cytoplasmic process of ~ 5μm in length. With degeneration, cluster number increased (~ 50%) but not significantly; however, the number of cells/cluster (P<0.001) and the percentage of cells forming clusters increased (P=0.0013). In the superficial zone but not the mid- or deep zones, the volume of clusters and average volume of chondrocytes in clusters increased (P<0.001 and P<0.05, respectively). The percentage of chondrocytes with processes, the number of processes/cell and the length of processes/cell increased in the superficial zone of grade-1 cartilage (P=0.0098, P=0.02 and P<0.001, respectively). Processes were categorised based on length (L0 - no cytoplasmic processes; L1<5μm; 5<L2≤10μm; 10<L3≤15μm; L4>15μm). With cartilage degeneration, for chondrocytes in all zones, there was a significant decrease (P=0.015) in the percentage of chondrocytes with 'normal' morphology (i.e. L0), with no change in the percentage of cells with L1 processes; however, there were significant increases in the other categories. In grade-0 cartilage, chondrocyte clustering and morphological abnormalities occurred and with degeneration these were exacerbated, particularly in the superficial zone. Chondrocyte clustering and abnormal morphology are associated with aberrant matrix metabolism, suggesting that these early changes to chondrocyte properties may be associated with cartilage degeneration.

Micrometer-Sized Magnesium Whitlockite Crystals in Micropetrosis of Bisphosphonate-Exposed Human Alveolar Bone.

Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bisphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed "micropetrosis". Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of ∼80 nm to ∼3 μm wide, distinctly faceted, magnesium whitlockite [Ca18Mg2(HPO4)2(PO4)12] crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae.

Peliosis Hepatis Complicating Pregnancy: A Rare Entity.

Peliosis hepatis (PH) is a rare, benign condition of the liver characterized by the presence of blood-filled lacunar spaces in the parenchyma. It usually has a chronic presentation and is a rare cause of portal hypertension reported in adult patients. Its etiology is diverse and ranges from infectious agents to tumors to toxic substances and anabolic steroids; however, the cause remains unclear in 25-50% of patients. Similarly, the symptomatology and imaging findings are diverse. Biopsy is the definitive test to diagnose the condition. Herein, we present a case of a young female presenting in her seventh month of gestational amenorrhea with signs of portal hypertension and subsequently diagnosed to have PH. She was managed conservatively and delivered her baby normally. Later, she presented with spontaneous bacterial peritonitis and hepatic encephalopathy and developed hepatorenal syndrome. She later succumbed to her illness. The condition should be kept in the differential diagnosis of the atypical liver masses and liver diseases causing portal hypertension.

Clinicopathological implications to micropapillary bladder urothelial carcinoma of the presence of sialyl Lewis X-decorated mucin 1 in stroma-facing membranes

ObjectivesBladder urothelial carcinoma (UC) comprises more than 90% of all bladder cancers. Among several UC variants, micropapillary UC (MPUC) is a rare one with high potential for lymphovascular invasion and subsequent lymph node metastasis. Histologically, MPUC is characterized by the presence of small papillary carcinoma cell clusters surrounded by lacunar spaces. Immunohistochemically, the outer circumference of these clusters, that is, the stroma-facing membrane of carcinoma cells, is reportedly almost invariably positive for mucin 1 (MUC1) protein and to a lesser extent for sialyl Lewis X (sLeX) carbohydrates; however, the clinicopathological implications of these expression patterns have not been fully investigated. Materials and methodsWe performed immunohistochemical analysis of MPUC (n = 11) and conventional UC (n = 57) for MUC1 and sLeX to determine whether these factors immunolocalized. Dual immunofluorescence staining was also carried out to assess MUC1 and sLeX colocalization. We also performed Western blot analysis of Chinese hamster ovary cells misexpressing both recombinant epitope-tagged MUC1 and glycosyltransferases enabling sLeX biosynthesis. ResultsMPUC samples preferentially exhibited both MUC1 protein and sLeX carbohydrate expression on the stroma-facing membrane of carcinoma cells. Based on univariate analysis, MUC1 expression in that pattern was positively correlated with tumor extension, lymphovascular invasion, lymph node metastasis, disease stage, and relatively poor patient prognosis. A comparable sLeX expression pattern also correlated positively with tumor extension and nodal metastasis. Based on multivariate analysis, localization of MUC1 and sLeX on the stroma-facing side of the membrane was positively correlated with lymph node metastasis. ConclusionsOverall, our immunofluorescence findings as well as immunoprecipitation analyses of Chinese hamster ovary cell transfectants strongly suggest that MUC1 is a potential scaffold protein for sLeX carbohydrates in MPUC. Both MUC1 and sLeX may cooperatively contribute to MPUC histogenesis and clinicopathological characteristics.

Evaluating differential nuclear DNA yield rates and osteocyte numbers among human bone tissue types: A synchrotron radiation micro-CT approach

Molecular human identification has conventionally focused on DNA sampling from dense, weight-bearing cortical bone tissue, typically from femora or tibiae. A comparison of skeletal elements from three contemporary individuals demonstrated that elements with high quantities of cancellous bone yielded nuclear DNA at the highest rates, suggesting that preferentially sampling cortical bone may be suboptimal (Mundorff & Davoren, 2014). Despite these findings, the reason for the differential DNA yields between cortical and cancellous bone tissues remains unknown. The primary goal of this work is to ascertain whether differences in bone microstructure can be used to explain differential nuclear DNA yield among bone tissue types observed by Mundorff and Davoren (2014), with a focus on osteocytes and the three-dimensional (3D) quantification of their associated lacunae. Osteocytes and other bone cells are recognized to house DNA in bone tissue, thus examining the density of their lacunae may explain why nuclear DNA yield rates differ among bone tissue types. Lacunae were visualized and quantified using synchrotron radiation-based micro-Computed Tomographic imaging (SR micro-CT). Volumes of interest (VOIs) from cortical and cancellous bone tissues (n=129) were comparatively analyzed from the three skeletons sampled for Mundorff and Davoren’s (2014) study. Analyses tested the primary hypothesis that the abundance and density of osteocytes (inferred from their lacunar spaces) vary between cortical and cancellous bone tissue types. Results demonstrated that osteocyte lacunar abundance and density vary between cortical and cancellous bone tissue types, with cortical bone VOIs containing a higher lacunar abundance and density. We found that the osteocyte lacunar density values are independent of nuclear DNA yield, suggesting an alternative explanation for the higher nuclear DNA yields from bones with greater quantities of cancellous bone tissue. The use of SR micro-CT allowed for a scale of analysis that revealed a high range of variation in lacunar abundance in both tissue types. Moreover, high-resolution SR micro-CT imaging revealed potential soft tissue remnants within marrow spaces not visible macroscopically. It is hypothesized that soft tissue remnants observed among the trabeculae of skeletal elements with high quantities of cancellous bone tissue are responsible for the high nuclear DNA yields. These findings have significant implications for bone-sample selection for nuclear DNA analysis in a forensic context when skeletal remains are recovered from the ground surface.

Bone Microvasculature Tracks Red Blood Cell Size Diminution in Triassic Mammal and Dinosaur Forerunners

Vertebrate red blood cells (RBCs) display a range ofsizes, spanning orders of magnitude in volume in different clades [1]. The importance of this size variation to diffusion during exercise is reinforced by functional links between RBC and capillary diameters [2, 3]. Small RBCs, such as those of mammals (which lack nuclei) and birds, contribute to shorter diffusion distances and permit relatively fast O2 uptake kinetics [4]. Although constraints on RBC size have been tied to the cell's need to attend capillary sizes for effective gas diffusion [3], as well as to genome size evolution [5, 6], major questions persist concerning patterns of RBC size evolution and its paleobiological significance. Here, we evaluate the relationship between RBC sizes and bone histometry and use microstructural evidence to trace their evolution in a phylogeny of extinct tetrapods. We find that several fossilizable aspects of bone microstructure, including the sizes of vascular and lacunar (cellular) spaces, provide useful indicators of RBC size in tetrapods. We also show that Triassic non-mammalian cynodonts had reduced and densely packed vascular canals identical to those of some mammals and likely accommodated smaller, more mammal-like RBCs. Reduced channel diameters accommodating smaller RBCs predated the origin of crown mammals by as much as 70 million years. This discovery offers a new proxy for the physiologic status of the mammal and avian stem groups and contextualizes the independent origins of their increased activity metabolism.

The Transdural Course of Radicular Spinal Cord Veins--A Microangiographical and Microscopical Study.

This study focuses on the following questions: What are the morphological features at the transdural course of radiculomedullary veins? How are these short transdural segments that may harbour pathological arteriovenous shunts connected to the internal vertebral venous plexus? Is the conception of a reflux-impeding mechanism at the transdural segment indispensable and convincing? A total of 102 radiculospinal veins were studied microscopically at various levels of the spinal canal using serial paraffin and semi-thin sections. In addition, 26 vessels were investigated microangiographically following orthograde (12) or attempted retrograde (14) opacification of the intradural venous segment with barium sulphate. After paraplast-embedding, contact-microradiographs were taken using high-resolution spectroscopic plates. At their transdural course, the veins showed narrowing of their lumen accompanied by changes in the vessel wall composition and a tortuous course. Two structurally distinct arrangements of the transdural segment could be identified: A slit type was seen in 60% of the veins studied and a bulge- or nodular type was seen in 35% of the veins. In total, 5% of cases could not be assigned to either one of these types. Reflux to radicular veins from the outside of the dura mater could be produced in 2 out of 14 specimens. The extradural venous plexus, which primarily receives the radicular vein, was composed more frequently of lacunar spaces rather than plexiform blood vessel convolutions. Rare observations were fibrotic, blind ending radiculomedullary veins and continuation of a distinct venous blood vessel after crossing the dura. Reflux from the epidural plexus to radicular veins is not reliably stopped at the dural level and possibly physiological. Different arrangements of the transdural course of the veins appear to be at least appropriate to modulate flow. The purpose for two different types of radicular vein exit is unclear. The clinical impact of disturbed reflux-control is uncertain, which is in stark contrast to the severe consequences resulting from dural arteriovenous shunts. The functional role of the probably predominant epidural venous plexus for the spinal cord blood circulation remains poorly understood.

Overexpression of Vascular Endothelial Growth Factor A in Invasive Micropapillary Colorectal Carcinoma.

Invasive micropapillary carcinoma (IMPC) is a rare variant of colorectal cancer with an adverse prognosis. "Retraction artifact" around tumor cells is a feature of IMPC. The aim of this study was to assess the nature of the retractions around the tumor cells and to describe the histopathological features of a group of 18 cases of IMPC. A pathology review of 128 consecutive colorectal cancers identified 18 cases of histologically proven IMPC using 5% of the total tumor volume comprised of a micropapillary component as the diagnostic criterion. Immunostains for D2-40, CD31, CD34, vascular endothelial growth factor A (VEGF-A), and mucin 1 (MUC-1) were performed using the avidin-biotin complex method. Cases of IMPC were characterized by pseudomicropapillae surrounded by lacunar-like clear spaces. These structures exhibited the inside-out growth pattern as highlighted by MUC-1 staining. The lining of the lacunar spaces was immunoreactive to CD31 but not CD34 or D2-40, indicating that they are neovascular structures. Furthermore, the tumor cells strongly and diffusely expressed VEGF-A. The strong coexpression of VEGF-A and CD31 suggests a prominent role of neoangiogenesis in these tumors.

Abstract No. 394 - Non-invasive vascular imaging and endovascular therapy for non-ischemic priapism

We aim to provide the reader with an educational depiction of the imaging findings and endovascular treatment options for non-ischemic priapism. A retrospective review of all the cases of non-ischemic priapism managed in our department in a period of 10 years: from August 2004 to August 2014. Specific examples of embolization cases were retrieved. We carried out a review of the current literature Non-ischemic (arterial, high-flow) priapism is usually the result of perineal or penile trauma. The injury results in a laceration in the cavernosal artery leading to the formation of a fistula between the artery and the lacunar spaces of the sinusoidal tissue. The diagnosis is usually made clinically and is aided by corporal blood aspiration and blood gas analysis. The role of non-invasive vascular imaging, both in diagnosis and in aiding conservative management (site specific perineal compression) is explored. Selective arterial embolization can be performed, usually after failure of conservative management. The relative merits of the different embolic agents used are summarised. The relevant angiographic anatomy is also presented. The operator must be familiar with the relevant anatomy including the critical variations which may necessitate alterations in technique. Non-ischemic priapism is a rare clinical entity that usually results from blunt trauma. Unlike ischemic priapism, it is not an emergency. Non-invasive vascular imaging can be performed to confirm the diagnosis and aid conservative management. Transarterial embolization can provide a definitive treatment in selected patients when conservative therapy has failed.

Ultrasound predictors of placental invasion: the Placenta Accreta Index

We sought to apply a standardized evaluation of ultrasound parameters for the prediction of placental invasion in a high-risk population. This was a retrospective review of gravidas with ≥1 prior cesarean delivery who received an ultrasound diagnosis of placenta previa or low-lying placenta in the third trimester at our institution from 1997 through 2011. Sonographic images were reviewed by an investigator blinded to pregnancy outcome and sonography reports. Parameters assessed included loss of retroplacental clear zone, irregularity and width of uterine-bladder interface, smallest myometrial thickness, presence of lacunar spaces, and bridging vessels. Diagnosis of placental invasion was based on histologic confirmation. Statistical analyses were performed using linear logistic regression and multiparametric analyses to generate a predictive equation evaluated using a receiver operating characteristic curve. Of 184 gravidas who met inclusion criteria, 54 (29%) had invasion confirmed on hysterectomy specimen. All sonographic parameters were associated with placental invasion (P < .001). Constructing a receiver operating characteristic curve, the combination of smallest sagittal myometrial thickness, lacunae, and bridging vessels, in addition to number of cesarean deliveries and placental location, yielded an area under the curve of 0.87 (95% confidence interval, 0.80-0.95). Using logistic regression, a predictive equation was generated, termed the "Placenta Accreta Index." Each parameter was weighted to create a 9-point scale in which a score of 0-9 provided a probability of invasion that ranged from 2-96%, respectively. Assignment of the Placenta Accreta Index may be helpful in predicting individual patient risk for morbidly adherent placenta.

Lamellar and Inverse Micellar Structures of Skin Lipids: Effect of Templating

The outermost layer of skin comprises rigid nonviable cells (corneocytes) in a layered lipid matrix. Using atomistic simulations we find that the equilibrium phase of the skin lipids is inverse micellar. A model of the corneocyte is used to demonstrate that lamellar layering is induced by the patterned corneocyte wall. The inverse micellar phase is consistent with in vivo observations in regions where corneocyte walls are well separated (lacunar spaces) and in the inner layers of skin, and suggests a functional role in the lipid synthesis pathway in vivo.

The transcriptional co-repressor TLE3 regulates development of trophoblast giant cells lining maternal blood spaces in the mouse placenta

TLE3 is a transcriptional co-repressor that interacts with several DNA-binding repressors, including downstream effectors of the Notch signaling pathway. We generated Tle3-deficient mice and found that they die in utero and their death is associated with abnormal development of the placenta with major defects in the maternal vasculature. In the normal placenta, maternal blood spaces are lined, not as usual in the mammalian circulation by endothelial cells, but rather by specialized embryo-derived cells of the trophoblast cell lineage named trophoblast giant cells (TGC). Tle3 mRNA is expressed in those specialized TGC and Tle3 mutants show severe defects in differentiation of TGC-lined channels and lacunar spaces that take blood out of the labyrinth zone of the placenta and into the uterine veins. The mutants also show somewhat milder defects on the arterial-side of the maternal vascular circuit in spiral arteries and canals that take blood into the labyrinth. Notch2 and Tle3 expression patterns overlap in several TGC subtypes and we found that Tle3 and Notch2 mutants have some overlapping features. However, they also show differences implying that TLE3 may mediate some but not all of the effects of Notch2 signaling during placenta development. Therefore, formation of the different types of maternal blood spaces by different TGC subtypes is regulated by distinct molecular mechanisms.

Osteocytes are not only mechanoreceptive cells

Osteocytes represent 95% of all bone cells. These cells are old osteoblasts occupying the lacunar space surrounded by the bone matrix. They possess cytoplasmic dendrites that form a canalicular network for communication between osteocytes and the bone surface. They have a mechanosensing role that is dependent upon the frequency, the intensity, and the duration of strain. The mechanical information transmitted into the cytoplasm also triggers a biological cascade, starting with nitric oxide and prostaglandin E 2 and followed by Wnt/ β-catenin signaling. This information is transmitted to the bone surface through the canalicular network, particularly to the lining cells, and is able to trigger bone remodeling by directing the osteoblast activity and the osteoclastic resorption. Furthermore, the osteocyte death seems to play an important role. The outcome of microcracks in the vicinity of osteocytes may interrupt the canalicular network and trigger cell apoptosis in the immediate surrounding environment thus transmitting a message to the bone surface and activate remodeling. This network also plays a recognized endocrine role, particularly concerning phosphate regulation and vitamin D metabolism.

3D Assessment of Cortical Bone Porosity and Tissue Mineral Density Using High-Resolution µCT: Effects of Resolution and Threshold Method

Current micro-computed tomography (µCT) systems allow scanning bone at resolutions capable of three-dimensional (3D) characterization of intracortical vascular porosity and osteocyte lacunae. However, the scanning and reconstruction parameters along with the image segmentation method affect the accuracy of the measurements. In this study, the effects of scanning resolution and image threshold method in quantifying small features of cortical bone (vascular porosity, vascular canal diameter and separation, lacunar porosity and density, and tissue mineral density) were analyzed. Cortical bone from the tibia of Sprague-Dawley rats was scanned at 1-µm and 4-µm resolution, reconstructions were density-calibrated, and volumes of interest were segmented using approaches based on edge-detection or histogram analysis. In 1-µm resolution scans, the osteocyte lacunar spaces could be visualized, and it was possible to separate the lacunar porosity from the vascular porosity. At 4-µm resolution, the vascular porosity and vascular canal diameter were underestimated, and osteocyte lacunae were not effectively detected, whereas the vascular canal separation and tissue mineral density were overestimated compared to 1-µm resolution. Resolution had a much greater effect on the measurements than did threshold method, showing partial volume effects at resolutions coarser than 2 µm in two separate analyses, one of which assessed the effect of resolution on an object of known size with similar architecture to a vascular pore. Although there was little difference when using the edge-detection versus histogram-based threshold approaches, edge-detection was somewhat more effective in delineating canal architecture at finer resolutions (1-2 µm). In addition, use of a high-resolution (1 µm) density-based threshold on lower resolution (4 µm) density-calibrated images was not effective in improving the lower-resolution measurements. In conclusion, if measuring cortical vascular microarchitecture, especially in small animals, a µCT resolution of 1 to 2 µm is appropriate, whereas a resolution of at least 1 µm is necessary when assessing osteocyte lacunar porosity.

Assessment of the effect of low-energy diode laser irradiation on gamma irradiated rats’ mandibles

ObjectiveThe purpose of the present study was to evaluate the biostimulative and regenerative effects of low intensity laser irradiation (LILT) (applied before or after initiation of radiotherapy) on gamma irradiated rats’ jaw bones. MethodsForty eight male Albino rats were equally divided into two groups: group 1, in which the left side of the mandible was subjected to three successive sessions of laser (LILT) prior to whole body gamma radiation (2Gy/3 fractions/week) and group 2, received whole body gamma radiation (2Gy/3 fractions/week) prior to three successive sessions of laser applied to left side. The right side of both groups was used as gamma irradiated non-lased control group. Each group was then subdivided into four equal subgroups (a, b, c, d) according to the time of scarification (3, 7, 14, 21 days respectively). Specimens were subjected to histological, histomorphometric and scanning electron microscopic examinations. ResultsThin irregular bone trabeculae and widened marrow spaces were identified in the control group. The lased sides of groups 1 and 2 demonstrated regular, thick and continuous bone trabeculae. Ultrastructurally, collagen fibres of the control group appeared irregularly arranged and more spaced compared to groups 1 and 2. Normal-sized osteocytic lacunae were seen in the lased groups, as compared to the wide lacunar spaces noted in the control group. Histomorphometric analysis showed a significant increase in the area of bone trabeculae, as well as the width of compact bone, for the lased groups. ConclusionsLILT seemed to attenuate the radiation-related damage in alveolar bones.

Metastatic Chondrosarcoma in a Corn Snake (Pantherophis guttatus)

An approximately two-year-old corn snake (Pantherophis guttatus) presented with a swelling of the mandible. The animal was treated for two months with no response. Unfortunately, the snake's condition deteriorated and it was euthanized. Grossly, the mass in the mandible was yellow–white and replaced normal bone and soft tissue of the jaw. Additional masses were noted in the heart, kidney, lung, pancreas, and eye. The mass in the mandible was comprised of a sheet of amorphous basophilic material resembling typical cartilage matrix with slightly irregular lacunar spaces. Tumor cells had abundant cytoplasm, vesicular or hyperchromatic nuclei, and prominent nucleoli. Mitotic figures were not seen. Scattered foci of neoplastic cartilaginous cells were noted in the heart, lung, kidney, pancreas, and eye. The final diagnosis for this case was secondary chondrosarcoma. Chondrosarcomas are not considered a common form of neoplasia in reptiles. When it is diagnosed, it appears to be more commonly associated with the vertebral column. Chondrosarcomas should be considered in the differential list for snakes (or other reptiles) that present with masses associated with the bone or cartilage.

Pre-embolization evaluation of high-flow priapism: magnetic resonance angiography of the penis

High-flow priapism is often a sequela of perineal trauma resulting in an arteriocavernosal fistula (ACF) between a cavernosal artery and lacunar spaces of the penis. We report our experience utilizing magnetic resonance angiography (MRA) in addition to color Doppler Sonography (CDS) in the workup and treatment planning of 4 patients with high-flow priapism. All patients had suspected high-flow priapism diagnosed by clinical exam and CDS and underwent MRA of the penis prior to sub-selective arterial embolization (SSAE) of the feeding vessel(s). While CDS is valuable in diagnosing and lateralizing high-flow priapism, it does not provide clear anatomic delineation of the number and origin of feeding vessels. MRA provided demonstration of the fistula, demonstrated bilateral ACF supply in 2 patients, and afforded three-dimensional display of the feeding vessels which facilitated pre-embolization planning. In all four cases, MRA was an effective tool for displaying arterial and venous anatomy, localizing the ACF, and planning subsequent SSAE. MRA influenced management in two out of 4 patients by demonstrating bilateral feeding vessels to their ACFs that required bilateral SSAE.

Ultrastructural immunolocalization of dentin matrix protein 1 on Sharpey's fibers in monkey tooth cementum

Despite the importance of dentin matrix protein 1 (DMP1) in the formation of mineralized tissue, including dentinogenesis and osteogenesis, its precise role in cementogenesis remains to be clarified fully. The purpose of our study was to demonstrate the ultrastructural immunolocalization of DMP1 in monkey molar tooth cementum. Japanese Macaca fuscata monkeys were fixed by perfusion. The upper molar teeth and accompanying periodontium then were dissected and demineralized with EDTA. Cryosections were obtained, incubated in anti-DMP1 polyclonal antibody, and processed by immunoperoxidase and immunogold labeling. Intense immunoperoxidase staining for DMP1 was observed in acellular extrinsic fiber cementum, particularly in Sharpey's fibers. Cementocyte lacunae with canaliculi showed DMP1 staining in the apical region of the tooth root. Electron immunomicroscopy revealed the close proximity of DMP1 to collagen fibrils in Sharpey's fibers at the mineralization front. Intense immunogold labeling was localized on the walls of the cementocyte lacunae in cellular cementum. These results should contribute to better understanding of the role of DMP1, not only in Sharpey's fiber biomineralization, but also in the maintenance of the cementocyte lacunar space in cementum.

A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors

Angiomotin (Amot) is one of several identified angiostatin receptors expressed by the endothelia of angiogenic tissues. We have shown that a DNA vaccine targeting Amot overcome immune tolerance and induce an antibody response that hampers the progression of incipient tumors. Following our observation of increased Amot expression on tumor endothelia concomitant with the progression from pre-neoplastic lesions to full-fledged carcinoma, we evaluated the effect of anti-Amot vaccination on clinically evident tumors. Electroporation of plasmid coding for the human Amot (pAmot) significantly delayed the progression both of autochthonous tumors in cancer prone BALB-neuT and PyMT genetically engineered mice and transplantable TUBO tumor in wild-type BALB/c mice. The intensity of the inhibition directly correlated with the titer of anti-Amot antibodies induced by the vaccine. Tumor inhibition was associated with an increase of vessels diameter with the formation of lacunar spaces, increase in vessel permeability, massive tumor perivascular necrosis and an effective epitope spreading that induces an immune response against other tumor associated antigens. Greater tumor vessel permeability also markedly enhances the antitumor effect of doxorubicin. These data provide a rationale for the development of novel anticancer treatments based on anti-Amot vaccination in conjunction with chemotherapy regimens.Electronic supplementary materialThe online version of this article (doi:10.1007/s10456-012-9263-3) contains supplementary material, which is available to authorized users.