Low grade fibromyxoid sarcoma: report of a case with fine needle aspiration cytology and histologic correlation

BACKGROUND: Low grade fibromyxoid sarcoma has been fully described histologically; however, the fine needle aspiration (FNA) cytologic findings are scantily defined, and the distinction from other benign and malignant soft tissue tumors can be difficult. CASE: We examined FNA cytologic material from a slowly growing, large chest wall mass in a 28-year-old woman. The surgical specimen was processed for routine histology and immunohistochemical studies. The cytologic smears were adequately cellular, showing spindly cells with uniform, elongated nuclei; small, inconspicuous nucleoli; and scanty, wispy cytoplasm associated with myxoid material. No significant nuclear pleomorphism or mitoses were noted. The excised tumor was well circumscribed, focally infiltrating the surrounding muscles. The cut surface was variable, featuring fibrous, solid, fleshy and myxoid areas. Microscopically, the solid, fibrous areas displayed increased cellularity with storiform, intersecting and parallel patterns. In the myxoid areas the cells grew in a haphazard fashion and appeared floating in abundant mucoid matrix associated with a capillary vascular network similar to the chicken-wire pattern seen in cases of myxoid liposarcoma. The tumor cells were spindly, with fusiform, uniform nuclei. Focal, moderate nuclear pleomorphism was noted. The mitotic index was low. The tumor cells were positive for vimentin, alpha-1-antitrypsin and lysozyme and negative for S-100, actin, desmin and CD34. CONCLUSION: Although low grade fibromyxoid sarcoma is a rare neoplasm, it should be recognized and distinguished from other soft tissue tumors because of its low malignant potential. The definitive FNA cytologic diagnosis can be challenging but is possible if the tumor is adequately sampled, with multiple passes from different areas. Clinical and radiologic correlations are of great help. All spindle cell tumors with myxoid changes, such as myxoid liposarcoma, myxofibrosarcoma, cellular myxoma, myxoid leiomyosarcoma and peripheral nerve sheath tumors, should be considered in the differential diagnosis. In contrast to the cytologic features, the histologic findings are characteristic and well established.     

Proteomic analysis of serum opsonins impacting biodistribution and cellular association of porous silicon microparticles

Mass transport of drug delivery vehicles is guided by particle properties, such as size, shape, composition, and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two-dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light variable chain, fibrinogen, and complement component 1 compared to their anionic counterparts. Anionic microparticles were found to accumulate in equal abundance in murine liver and spleen, whereas cationic microparticles showed preferential accumulation in the spleen. Immunohistochemistry supported macrophage uptake of both anionic and cationic microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution.     

Rap1 regulates E-cadherin-mediated cell-cell adhesion

The small GTPase Rap is best characterized as a critical regulator of integrin-mediated cell adhesion, although its mechanism of action is not understood. Rap also influences the properties of other cell-surface receptors and biological processes, although whether these are a consequence of effects on integrins is not clear. We show here that Rap also plays an important role in the regulation of cadherin-mediated cell-cell adhesion in epithelial cells. Expression of constitutively active Rap1A restored cadherin-mediated cell-cell contacts in mesenchymal Ras-transformed Madin-Darby canine kidney cells, resulting in reversion to an epithelial phenotype. Activation of endogenous Rap via the Rap exchange factor Epac1 also antagonized hepatocyte growth factor-induced disruption of adherens junctions. Inhibition of Rap signaling resulted in disruption of epithelial cell-cell contacts. Rap activity was required for adhesion of cells to recombinant E-cadherin extracellular domains, i.e. in the absence of integrin-mediated adhesion. These findings suggest that Rap signaling positively contributes to cadherin-mediated adhesion and that this occurs independently of effects on integrin-mediated adhesion. Our results imply that Rap may function in a broader manner to regulate the function of cell-surface adhesion receptors.     

Comparison of the results of surgical and non-surgical treatment of combat urogenital injuries in Bosnia war 1992-1995

Goal was to compare the results of surgical and non-surgical treatments of combat injuries of genitourinary system and to compare our data with data collected in the recent studies. The study was designed as a retrospective review of data collected in prospective databases. The data extracted from inpatients' medical records included demographics, mechanisms and type of injury, distribution of the lesions, clinical presentation features, applied diagnostic studies, treatment modalities, types of complication and results of treatment. Among 4.125 patients treated in the Mostar War Hospital, 111 had injury of genitourinary tract: 62 underwent a surgical and 49 non-surgical treatment. Mortality among operated patients was 16 (26%). Complications were noted in 47 patients (42%); in 33 (70%) were manifested as early complications, and 14 (30) as delayed ones (p = 0.006). Among the surgically treated patients, 40 (36%) had some complication, in comparison to 8 (7.2%) patients with complications among non-surgically treated patients; which represent a statistically significant difference (p < 0.05). In this study, there was a surprisingly high number of non-surgically treated patients, and this sub-group of UGT trauma patients had in some ways the superior treatment results in comparison with surgically treated patients. Conservatively treated patients had lower rate of complications, no mortality, and no patients with permanent disability.     

Increased lipolysis but diminished gene expression of lipases in subcutaneous adipose tissue of healthy young males with intrauterine growth retardation

Intrauterine growth retardation (IUGR) is associated with a central fat distribution and risk of developing type 2 diabetes in adults when exposed to a sedentary Western lifestyle. Increased lipolysis is an early defect of metabolism in IUGR subjects, but the sites and molecular mechanisms involved are unknown. Twenty IUGR and 20 control (CON) subjects, aged 20-30 years, were studied before and after 10 days of bed rest using the glucose clamp technique combined with measurements of in vivo metabolism by microdialysis technique and blood flow by (133)Xe washout technique in subcutaneous abdominal (SCAAT) and femoral (SCFAT) adipose tissue. Additionally, mRNA expression of lipases was evaluated in biopsies from SCAAT. Lipolysis in SCAAT was substantially higher in IUGR than in CON subjects despite markedly lower mRNA expression of lipases. Blood flow was higher in IUGR compared with CON in both SCAAT and SCFAT. Whole body insulin sensitivity did not differ between groups and decreased after bed rest. After bed rest, SCAAT lipolysis remained higher in IUGR compared with CON, and SCFAT lipolysis decreased in CON but not in IUGR. Prior to the development of whole body insulin resistance, young men with IUGR are characterized by increased in vivo adipose tissue lipolysis and blood flow with a paradoxically decreased expression of lipases compared with CON, and 10 days of physical inactivity underlined the baseline findings. Subjects with IUGR exhibit primary defects in adipose tissue metabolism.     

Destruction of aflatoxins B1 and G1 in bread making

The effect of processing steps as well preservatives used in French bread making namely propionic acid and/or potassium sorbate (0.2%) on the destruction of aflatoxins B₁ and G₁ was studied. Mixing and baking processes showed marked destruction of aflatoxins B₁ and G₁; being 71.2% and 52.5% for aflatoxin B₁ after mixing and baking steps, while reaching 73.9% and 54.5% for aflatoxin G₁. Fermentation step caused additional 15.3% and 15.0% destruction of aflatoxins B₁ and G₁. On the other hand, aflatoxin B₁ destruction was 79.2% and 50.7% when propionic acid was used and 75.3 and 56.7% in the presence of potassium sorbate and after mixing and baking steps respectively. Concerning aflatoxins G₁ it was found that mixing and baking steps showed destruction of 81.9% and 53.4% in the presence of propionic acid and 75.1 and 49.4% in the presence of potassium sorbate in this respective order. Generally, it can be concluded that using propionic acid as preservative appeared to be more effective on the destruction of aflatoxins B₁ and G₁ than potassium sorbate in French bread making.     

Potential protective effect of HSCAS and bentonite against dietary aflatoxicosis in rat: with special reference to chromosomal aberrations.

Bentonite and hydrated sodium calcium aluminsilicate (HSCAS) were added at a level of 0.5% (w/w) to the diets containing 2.5 mg aflatoxins (AF) per kg diet and fed to male mature rats for 15 successive days. Aflatoxin alone significantly decreased feed intake and altered serum biochemical parameters of liver and kidney functions. Aflatoxin caused chromosomal aberrations in bone marrow cells. Bentonite or HSCAS did not alter any of the parameters measured. The addition of bentonite or HSCAS to the AF-contaminated diet diminished most of the deleterious effects of the aflatoxin. Pathological examinations of liver and kidney proved that both bentonite and HSCAS were hepatonephroprotective agents against aflatoxicosis. The cytogenetic findings demonstrated that the addition of bentonite or HSCAS to AF-contaminated diet suppressed chromosomal aberrations. These findings indicated that bentonite and HSCAS could diminished many of the adverse effect of dietary AF in rats.     

The hierarchical packing of euchromatin domains can be described as multiplicative cascades

The genome is packed into the cell nucleus in the form of chromatin. Biochemical approaches have revealed that chromatin is packed within domains, which group into larger domains, and so forth. Such hierarchical packing is equally visible in super-resolution microscopy images of large-scale chromatin organization. While previous work has suggested that chromatin is partitioned into distinct domains via microphase separation, it is unclear how these domains organize into this hierarchical packing. A particular challenge is to find an image analysis approach that fully incorporates such hierarchical packing, so that hypothetical governing mechanisms of euchromatin packing can be compared against the results of such an analysis. Here, we obtain 3D STED super-resolution images from pluripotent zebrafish embryos labeled with improved DNA fluorescence stains, and demonstrate how the hierarchical packing of euchromatin in these images can be described as multiplicative cascades. Multiplicative cascades are an established theoretical concept to describe the placement of ever-smaller structures within bigger structures. Importantly, these cascades can generate artificial image data by applying a single rule again and again, and can be fully specified using only four parameters. Here, we show how the typical patterns of euchromatin organization are reflected in the values of these four parameters. Specifically, we can pinpoint the values required to mimic a microphase-separated state of euchromatin. We suggest that the concept of multiplicative cascades can also be applied to images of other types of chromatin. Here, cascade parameters could serve as test quantities to assess whether microphase separation or other theoretical models accurately reproduce the hierarchical packing of chromatin.     

Vac14 Protein Multimerization Is a Prerequisite Step for Fab1 Protein Complex Assembly and Function

Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P₂) helps control various endolysosome functions including organelle morphology, membrane recycling, and ion transport. Further highlighting its importance, PtdIns(3,5)P₂ misregulation leads to the development of neurodegenerative diseases like Charcot-Marie-Tooth disease. The Fab1/PIKfyve lipid kinase phosphorylates PtdIns(3)P into PtdIns(3,5)P₂ whereas the Fig4/Sac3 lipid phosphatase antagonizes this reaction. Interestingly, Fab1 and Fig4 form a common protein complex that coordinates synthesis and degradation of PtdIns(3,5)P₂ by a poorly understood process. Assembly of the Fab1 complex requires Vac14/ArPIKfyve, a multimeric scaffolding adaptor protein that coordinates synthesis and turnover of PtdIns(3,5)P₂. However, the properties and function of Vac14 multimerization remain mostly uncharacterized. Here we identify several conserved C-terminal motifs on Vac14 required for self-interaction and provide evidence that Vac14 likely forms a dimer. We also show that monomeric Vac14 mutants do not support interaction with Fab1 or Fig4, suggesting that Vac14 multimerization is likely the first molecular event in the assembly of the Fab1 complex. Finally, we show that cells expressing monomeric Vac14 mutants have enlarged vacuoles that do not fragment after hyperosmotic shock, which indicates that PtdIns(3,5)P₂ levels are greatly abated. Therefore, our observations support an essential role for the Vac14 homocomplex in controlling PtdIns(3,5)P₂ levels.     

Social Contact Networks and Mixing among Students in K-12 Schools in Pittsburgh,PA

Students attending schools play an important role in the transmission of influenza. In this study, we present a social network analysis of contacts among 1,828 students in eight different schools in urban and suburban areas in and near Pittsburgh, Pennsylvania, United States of America, including elementary, elementary-middle, middle, and high schools. We collected social contact information of students who wore wireless sensor devices that regularly recorded other devices if they are within a distance of 3 meters. We analyzed these networks to identify patterns of proximal student interactions in different classes and grades, to describe community structure within the schools, and to assess the impact of the physical environment of schools on proximal contacts. In the elementary and middle schools, we observed a high number of intra-grade and intra-classroom contacts and a relatively low number of inter-grade contacts. However, in high schools, contact networks were well connected and mixed across grades. High modularity of lower grades suggests that assumptions of homogeneous mixing in epidemic models may be inappropriate; whereas lower modularity in high schools suggests that homogenous mixing assumptions may be more acceptable in these settings. The results suggest that interventions targeting subsets of classrooms may work better in elementary schools than high schools. Our work presents quantitative measures of age-specific, school-based contacts that can be used as the basis for constructing models of the transmission of infections in schools.