Primary Cutaneous Follicular Helper T-Cell Lymphoma: A Case Series and Review of the Literature.

Primary cutaneous follicular helper T-cell (Tfh) lymphoma is a recently described variant of peripheral T-cell lymphoma-not otherwise specified. This particular variant, usually presenting as a sudden onset of multiple plaques and nodules, is characterized by tumoral atypical T cells that express an array of Tfh markers, such as inducible T-cell costimulator, Bcl-6, CXCL13, PD-1, and CD10. The authors now present 3 patients whose known clinical skin findings are consistent with PTCL of Tfh origin (PTCL-Tfh). The typically protracted pattern of skin disease manifesting as scaly patches and plaques encountered in mycosis fungoides was not seen in our 3 cases, and there were distinguishing light microscopic and phenotypic features. These cases are similar to the few previous reported cases of PTCL-Tfh, although systemic involvement was not seen. The categorization of additional patients into this PTCL subtype in the medical literature would be needed to further characterize this new entity and may lead to better targeted treatments based on specific T-cell subtypes.

Reexcision Perineural Invasion and Epithelial Sheath Neuroma Possibly on a Spectrum of Postinjury Reactive Hyperplasia Mediated by IL-6.

Epithelial sheath neuroma is a rarely recognized but established entity in the medical literature. First described in 2000 by Requena et al, there have only been 7 published cases to date, mostly in female patients and presenting as symptomatic solitary lesions on the back without a known history of trauma. In 2006, Beer et al described and reviewed a dozen cases in which epithelial sheath neuroma-like features were seen in the advent of a surgical procedure, which was termed "re-excision perineural invasion" and attributed to possible eccrine duct implantation during surgery. Our case is a 66-year-old male patient who underwent an excision of a melanocytic neoplasm in which a reactive epithelial sheath neuroma was incidentally discovered in the excision specimen, adjacent to the biopsy site cicatrix. Histologically, there was benign cutaneous nerve hyperplasia with a proliferation of squamous epithelium in intimate apposition to the nerve bundles in the superficial dermis. We postulate that the process active in the formation of re-excision perineural invasion is the same as in epithelial sheath neuroma and that minor trauma not appreciable on histologic examination is responsible in the latter entity. We performed IL-6 staining and documented that IL-6 was upregulated at the interface of the nerve and reactive epithelium, but was absent in nerves distant from the site of surgery, suggesting that IL-6 may be essential to the lesion's development. The recognition of reactive epithelial sheath neuroma including the subcategory of re-excision perineural invasion is crucial for the dermatopathologist to prevent mislabeling this reactive entity as a perineural squamous cell carcinoma, which has clinical consequences for the patient such as wider re-excision and radiation treatment. Additionally, we have identified a potential pathophysiologic basis for this lesion.

An Index Case of Concomitant Tumoral and Ichthyosiform Mycosis Fungoides-Like Presentation of Chronic Adult T-cell Leukemia/Lymphoma Associated With Upregulation of TOX.

Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities. Histopathologic examination of the hand biopsy revealed coalescing nodules of large atypical noncerebriform lymphocytes with focal areas of epidermotropism. Phenotypically, the infiltrate was positive for ß-F1, CD2, CD4, CD5, CD7, Foxp3, and CD25. In both biopsies, there was striking upregulation of TOX (thymocyte selection-associated high mobility group box factor) in the nuclei of neoplastic cells. The second biopsy taken from the ichthyotic patch on the patient's left leg showed a subtle pattern of epidermal infiltration by atypical noncerebriform lymphocytes and a distinct compact scale consistent with the clinical picture of ichthyosis. The histopathologic appearance was that of a yet undescribed ichthyosiform mycosis fungoides-like presentation of chronic ATLL. In addition, the observed upregulation of nuclear TOX may play an oncogenic role in ATLL. The course to date in this patient has been relatively indolent, although the patients believe that large cell transformation could portend more aggressive disease.

Natural bactericidal surfaces: mechanical rupture of Pseudomonas aeruginosa cells by cicada wings.

Natural superhydrophobic surfaces are often thought to have antibiofouling potential due to their self-cleaning properties. However, when incubated on cicada wings, Pseudomonas aeruginosa cells are not repelled; instead they are penetrated by the nanopillar arrays present on the wing surface, resulting in bacterial cell death. Cicada wings are effective antibacterial, as opposed to antibiofouling, surfaces.

Spatial variations and temporal metastability of the self-cleaning and superhydrophobic properties of damselfly wings.

Self-cleaning surfaces found in nature show great potential for application in many fields, ranging from industry to medicine. The ability for a surface to self-clean is intimately related to the wetting properties of the surface; for a surface to possess self-cleaning ability it must exhibit extremely high water contact angles and low water adhesion. While investigating the self-cleaning properties of damselfly wings, significant spatial variations in surface wettability were observed. Within an area of 100 µm × 100 µm of the wing surface the water contact angle was found to vary up to 17.8°, while remaining consistently superhydrophobic. The contributions of both surface chemistry and topography to the hydrophobicity of the wings were assessed in an effort to explain these variations. Synchrotron-sourced Fourier-transform infrared microspectroscopy revealed that some of the major components of the wing were aliphatic hydrocarbons and esters, which are attributable to epicuticular lipids. The wing topography, as determined by optical profilometry and atomic force microscopy (AFM), also showed only minor levels of heterogeneity arising from irregular ordering of surface nanostructures. The measured contact angle of a single droplet of water was also found to decrease over time as it evaporated, reaching a minimum of 107°. This is well below the threshold value for superhydrophobicity (i.e., 150°), demonstrating that when the surface is in contact with water for a prolonged period, the damselfly wings lose their superhydrophobicity and subsequently their ability to self-clean. This decrease in hydrophobicity over time can be attributed to the surface undergoing a transition from the Cassie-Baxter wettability state toward the Wenzel wettability state.

The influence of nanoscopically thin silver films on bacterial viability and attachment.

The physicochemical and bactericidal properties of thin silver films have been analysed. Silver films of 3 and 150 nm thicknesses were fabricated using a magnetron sputtering thin-film deposition system. X-ray photoelectron and energy dispersive X-ray spectroscopy and atomic force microscopy analyses confirmed that the resulting surfaces were homogeneous, and that silver was the most abundant element present on both surfaces, being 45 and 53 at.% on the 3- and 150-nm films, respectively. Inductively coupled plasma time of flight mass spectroscopy (ICP-TOF-MS) was used to measure the concentration of silver ions released from these films. Concentrations of 0.9 and 5.2 ppb were detected for the 3- and 150-nm films, respectively. The surface wettability of the films remained nearly identical for both film thicknesses, displaying a static water contact angle of 95°, while the surface free energy of the 150-nm film was found to be slightly greater than that of the 3-nm film, being 28.8 and 23.9 mN m(-1), respectively. The two silver film thicknesses exhibited statistically significant differences in surface topographic profiles on the nanoscopic scale, with R (a), R (q) and R (max) values of 1.4, 1.8 and 15.4 nm for the 3-nm film and 0.8, 1.2 and 10.7 nm for the 150-nm film over a 5 × 5 µm scanning area. Confocal scanning laser microscopy and scanning electron microscopy revealed that the bactericidal activity of the 3-nm silver film was not significant, whereas the nanoscopically smoother 150-nm silver film exhibited appreciable bactericidal activity towards Pseudomonas aeruginosa ATCC 9027 cells and Staphylococcus aureus CIP 65.8 cells, obtaining up to 75% and 27% sterilisation effect, respectively.

The prostaglandin D2 receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge.

BACKGROUND: Cutaneous prostaglandin (PG) D2 levels increase after scratching. Chemoattractant receptor-homologous molecule expressed on receptor on T(H)2 cells (CRTH2) mediates chemotaxis to PGD2 and is expressed on T(H)2 cells and eosinophils, which infiltrate skin lesions in patients with atopic dermatitis. OBJECTIVE: We sought to examine the role of CRTH2 in a murine model of atopic dermatitis. METHODS: CRTH2(-/-) mice and wild-type control animals were epicutaneously sensitized by means of repeated application of ovalbumin (OVA) to tape-stripped skin for 7 weeks and then challenged by means of OVA application to tape-stripped previously unsensitized skin for 1 week. Skin histology was assessed by means of hematoxylin and eosin staining and immunohistochemistry. Cytokine mRNA expression was examined by means of quantitative RT-PCR. Levels of PGD2, antibody, and cytokines were measured by means of ELISA. RESULTS: PGD2 levels significantly increased in skin 24 hours after tape stripping, although not in skin subjected to repeated sensitization with OVA. Allergic skin inflammation developed normally at sites of chronic epicutaneous sensitization with OVA in CRTH2(-/-) mice but was severely impaired in previously unsensitized skin challenged with OVA, as evidenced by significantly decreased skin infiltration with eosinophils and CD4(+) cells and impaired T(H)2 cytokine mRNA expression. Impaired skin inflammation at sites of acute OVA challenge in CRTH2(-/-) mice was not due to an impaired systemic response to epicutaneous sensitization because OVA-specific IgG1 and IgE antibody levels and OVA-driven splenocyte secretion of cytokines in these mice were comparable with those seen in wild-type control animals. CONCLUSIONS: CRTH2 promotes allergic skin inflammation in response to cutaneous exposure to antigen in previously sensitized mice.

Impact of nanoscale roughness of titanium thin film surfaces on bacterial retention.

Two human pathogenic bacteria, Staphylococcus aureus CIP 68.5 and Pseudomonas aeruginosa ATCC 9025, were adsorbed onto surfaces containing Ti thin films of varying thickness to determine the extent to which nanoscale surface roughness influences the extent of bacterial attachment. A magnetron sputter thin film system was used to deposit titanium films with thicknesses of 3, 12, and 150 nm on glass substrata with corresponding surface roughness parameters of R(q) 1.6, 1.2, and 0.7 nm (on a 4 microm x 4 microm scanning area). The chemical composition, wettability, and surface architecture of titanium thin films were characterized using X-ray photoelectron spectroscopy, contact angle measurements, atomic force microscopy, three-dimensional interactive visualization, and statistical approximation of the topographic profiles. Investigation of the dynamic evolution of the Ti thin film topographic parameters indicated that three commonly used parameters, R(a), R(q), and R(max), were insufficient to effectively characterize the nanoscale rough/smooth surfaces. Two additional parameters, R(skw) and R(kur), which describe the statistical distributions of roughness character, were found to be useful for evaluating the surface architecture. Analysis of bacterial retention profiles indicated that bacteria responded differently to the surfaces on a scale of less than 1 nm change in the R(a) and R(q) Ti thin film surface roughness parameters by (i) an increased number of retained cells by a factor of 2-3, and (ii) an elevated level of secretion of extracellular polymeric substances.

Plasma-enhanced synthesis of bioactive polymeric coatings from monoterpene alcohols: a combined experimental and theoretical study.

This paper describes the synthesis and characterization of a novel organic polymer coating for the prevention of the growth of Pseudomonas aeruginosa on the solid surface of three-dimensional objects. Substrata were encapsulated with polyterpenol thin films prepared from terpinen-4-ol using radio frequency plasma enhanced chemical vapor deposition. Terpinen-4-ol is a constituent of tea tree oil with known antibacterial properties. The influence of deposition power on the chemical structure, surface composition, and ultimately the antibacterial inhibitory activity of the resulting polyterpenol thin films was studied using X-ray photoelectron spectroscopy (XPS), water contact angle measurement, atomic force microscopy (AFM), and 3-D interactive visualization and statistical approximation of the topographic profiles. The experimental results were consistent with those predicted by molecular simulations. The extent of bacterial attachment and extracellular polymeric substances (EPS) production was analyzed using scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). Polyterpenol films deposited at lower power were particularly effective against P. aeruginosa due to the preservation of original terpinen-4-ol molecules in the film structure. The proposed antimicrobial and antifouling coating can be potentially integrated into medical and other clinically relevant devices to prevent bacterial growth and to minimize bacteria-associated adverse host responses.

Effect of ultrafine-grained titanium surfaces on adhesion of bacteria.

The influence of the ultrafine crystallinity of commercial purity grade 2 (as-received) titanium and titanium modified by equal channel angular pressing (modified titanium) on bacterial attachment was studied. A topographic profile analysis of the surface of the modified titanium revealed a complex morphology of the surface. Its prominent micro- and nano-scale features were 100-200-nm-scale undulations with 10-15 microm spacing. The undulating surfaces were nano-smooth, with height variations not exceeding 5-10 nm. These surface topography characteristics were distinctly different from those of the as-received samples, where broad valleys (up to 40-60 microm) were detected, whose inner surfaces exhibited asperities approximately 100 nm in height spaced at 1-2 microm. It was found that each of the three bacteria strains used in this study as adsorbates, viz. Staphylococcus aureus CIP 68.5, Pseudomonas aeruginosa ATCC 9025 and Escherichia coli K12, responded differently to the two types of titanium surfaces. Extreme grain refinement by ECAP resulted in substantially increased numbers of cells attached to the surface compared to as-received titanium. This enhanced degree of attachment was accompanied with an increased level of extracellular polymeric substances (EPS) production by the bacteria.

Nab proteins are essential for peripheral nervous system myelination.

Mutations that disrupt Egr2 transcriptional activity cause severe demyelinating peripheral neuropathies. Here we provide evidence that Nab1 and Nab2 proteins are critical transcriptional modulators of Egr2 in myelinating Schwann cells. Like Egr2, these proteins are essential for Schwann cell differentiation into the myelinating state. Mice lacking both Nab1 and Nab2 show severe congenital hypomyelination of peripheral nerves, with Schwann cell development arresting at the promyelinating stage, despite elevated Egr2 expression. As observed for Egr2, Nab proteins are necessary for Schwann cells to exit the cell cycle, downregulate suppressed cAMP-inducible protein (SCIP) expression and upregulate expression of critical myelination genes. The mRNA expression signature of Schwann cells deficient in both Nab1 and Nab2 is highly similar to that of Egr2-deficient Schwann cells, further indicating that the Egr2/Nab protein complex is a key regulator of the Schwann cell myelination program and that disruption of this transcriptional complex is likely to result in Schwann cell dysfunction in patients with Egr2 mutations.

Misexpression of Pou3f1 results in peripheral nerve hypomyelination and axonal loss.

Pou3f1/SCIP/Oct-6 is a POU-domain transcription factor that is an important regulator of peripheral nerve myelination by Schwann cells. Pou3f1-deficient mice experience a developmental delay in myelination indicating that transient induction of Pou3f1 is required for normal development of peripheral myelin. The mechanism by which Pou3f1 regulates myelination is unclear, because it can both increase expression of Egr2, a transcription factor that promotes the myelination program, and also repress the promoters of specific myelin genes such as myelin protein zero (MPZ) and myelin basic protein (MBP). Therefore, to investigate the effects of persistent Pou3f1 expression on peripheral nerve myelination, we created a conditional transgenic mouse [condPou3f1:MPZ(Cre)] that constitutively expresses Pou3f1 specifically in peripheral glia. Examination of sciatic nerves from condPou3f1:MPZ(Cre) mice revealed persistent hypomyelination and eventual axonal loss but no evidence of demyelination/remyelination processes or impaired Schwann cell proliferation. Nerves from these mice had normal levels of Egr2 mRNA but decreased levels of MPZ, MBP, and Pmp22 mRNA. Thus, unlike the Pou3f1 null mice, the condPou3f1:MPZ(Cre) mice exhibit persistent hypomyelination, indicating that strict control of Pou3f1 expression is critical to proper myelination. Our findings establish the importance of identifying factor(s) responsible for Pou3f1 downregulation during myelination, because they may play important roles in the development of peripheral neuropathies.

Subtle Variations in Surface Properties of Black Silicon Surfaces Influence the Degree of Bactericidal Efficiency.

One of the major challenges faced by the biomedical industry is the development of robust synthetic surfaces that can resist bacterial colonization. Much inspiration has been drawn recently from naturally occurring mechano-bactericidal surfaces such as the wings of cicada (Psaltoda claripennis) and dragonfly (Diplacodes bipunctata) species in fabricating their synthetic analogs. However, the bactericidal activity of nanostructured surfaces is observed in a particular range of parameters reflecting the geometry of nanostructures and surface wettability. Here, several of the nanometer-scale characteristics of black silicon (bSi) surfaces including the density and height of the nanopillars that have the potential to influence the bactericidal efficiency of these nanostructured surfaces have been investigated. The results provide important evidence that minor variations in the nanoarchitecture of substrata can substantially alter their performance as bactericidal surfaces.

Cirrhosis in an Active Duty Soldier With Concomitant Isolated Polycystic Disease and H63D Homozygosity.

We report the case of a 45-year-old male soldier who was evaluated for a rapidly expanding hepatic mass following cholecystectomy and was eventually found to have isolated polycystic liver disease and express HFE H63D homozygosity. Both H63D homozygosity and isolated polycystic liver disease are only rarely associated with clinical cirrhosis. This is the first reported case of their concomitant presentation.

Persistent parity-induced changes in growth factors, TGF-beta3, and differentiation in the rodent mammary gland.

Epidemiological studies have repeatedly demonstrated that women who undergo an early first full-term pregnancy have a significantly reduced lifetime risk of breast cancer. Similarly, rodents that have previously undergone a full-term pregnancy are highly resistant to carcinogen-induced breast cancer compared with age-matched nulliparous controls. Little progress has been made, however, toward understanding the biological basis of this phenomenon. We have used DNA microarrays to identify a panel of 38 differentially expressed genes that reproducibly distinguishes, in a blinded manner, between the nulliparous and parous states of the mammary gland in multiple strains of mice and rats. We find that parity results in the persistent down-regulation of multiple genes encoding growth factors, such as amphiregulin, pleiotrophin, and IGF-1, as well as the persistent up-regulation of the growth-inhibitory molecule, TGF-beta3, and several of its transcriptional targets. Our studies further indicate that parity results in a persistent increase in the differentiated state of the mammary gland as well as lifelong changes in the hematopoietic cell types resident within the gland. These findings define a developmental state of the mammary gland that is refractory to carcinogenesis and suggest novel hypotheses for the mechanisms by which parity may modulate breast cancer risk.

Antibacterial titanium nano-patterned arrays inspired by dragonfly wings.

Titanium and its alloys remain the most popular choice as a medical implant material because of its desirable properties. The successful osseointegration of titanium implants is, however, adversely affected by the presence of bacterial biofilms that can form on the surface, and hence methods for preventing the formation of surface biofilms have been the subject of intensive research over the past few years. In this study, we report the response of bacteria and primary human fibroblasts to the antibacterial nanoarrays fabricated on titanium surfaces using a simple hydrothermal etching process. These fabricated titanium surfaces were shown to possess selective bactericidal activity, eliminating almost 50% of Pseudomonas aeruginosa cells and about 20% of the Staphylococcus aureus cells coming into contact with the surface. These nano-patterned surfaces were also shown to enhance the aligned attachment behavior and proliferation of primary human fibroblasts over 10 days of growth. These antibacterial surfaces, which are capable of exhibiting differential responses to bacterial and eukaryotic cells, represent surfaces that have excellent prospects for biomedical applications.

A systems analysis tool for construction and demolition wastes management.

Managing construction and demolition (C&D) wastes has challenged many municipalities with diminishing waste disposal capacity. Facing such challenges, the Massachusetts Department of Environmental Protection proposed a policy restricting the landfill disposal of certain C&D waste materials, if unprocessed. This research is to study the potential economic impact of such restriction on construction contractors and C&D waste processors. A spreadsheet-based systems analysis model has been developed to assist the cost-benefit evaluation for various C&D waste management scenarios. The model, developed based on the mass balance principle, is designed to track a C&D waste stream through the various stages of a waste management system, i.e. generation, source separation, processing, recycling, and final disposal. This model, by incorporating the material flow data with the cost/revenue data associated with each management activity, can then provide an economic analysis for a proposed C&D waste management scenario. A case study illustrating the application of this model for Massachusetts is also presented.

Overcoming the "coffee-stain" effect by compositional Marangoni-flow-assisted drop-drying.

Attempts at depositing uniform films of nanoparticles by drop-drying have been frustrated by the "coffee-stain" effect due to convective macroscopic flow into the contact line. Here, we show that uniform deposition of nanoparticles in aqueous suspensions can be attained easily by drying the droplet in an ethanol vapor atmosphere. This technique allows the particle-laden water droplets to spread on a variety of surfaces such as glass, silicon, mica, PDMS, and even Teflon. Visualization of droplet shape and internal flow shows initial droplet spreading and strong recirculating flow during spreading and shrinkage. The initial spreading is due to a diminishing contact angle from the absorption of ethanol from the vapor at the contact line. During the drying phase, the vapor is saturated in ethanol, leading to preferential evaporation of water at the contact line. This generates a surface tension gradient that drives a strong recirculating flow and homogenizes the nanoparticle concentration. We show that this method can be used for depositing catalyst nanoparticles for the growth of single-walled carbon nanotubes as well as to manufacture plasmonic films of well-spaced, unaggregated gold nanoparticles.