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MCC
Selected AbstractsThe potential contribution of fluorescent in situ hybridization analysis to the cytopathological diagnosis of Merkel cell carcinomaCYTOPATHOLOGY, Issue 1 2008V. Suciu We report the cases of two patients with head and neck Merkel cell carcinoma (MCC) who developed local recurrences confirmed by cytopathology. Interphase fluorescent in situ hybridization (FISH) analysis was performed for research purposes using centromeric probes of chromosomes 6 and 8, on cytological slides. Trisomy of chromosome 6 was found in 85% of tumour cells in the first case of MCC and case 2 exhibited trisomy 8 in 77% of tumour cells. In the absence of specific molecular markers, detection of trisomy 6 and/or trisomy 8 could help in identifying MCC. FISH analysis is easily and quickly performed on interphase nuclei obtained through fine needle aspiration and may be extended to the study of other relevant genetic abnormalities. [source] Mohs Micrographic Surgery in the Treatment of Rare Aggressive Cutaneous Tumors: The Geisinger ExperienceDERMATOLOGIC SURGERY, Issue 3 2007CHADWICK JOHN THOMAS MD BACKGROUND Mohs micrographic surgery (MMS) offers high cure rates and maximum tissue preservation in the treatment of more common cutaneous malignancies, but its effectiveness in rare aggressive tumors is poorly defined. OBJECTIVE Evaluate the effectiveness of MMS in the treatment of six rare aggressive cutaneous malignancies as seen by Mohs surgeons working at a referral center. METHODS Retrospective chart review of 26,000 cases treated with MMS at the Geisinger Medical Center Department of Dermatology during a 16-year period with the following diagnoses: poorly differentiated squamous cell carcinoma (PDSCC), dermatofibrosarcoma protuberans (DFSP), microcystic adnexal carcinoma (MAC), extramammary Paget's disease (EMPD), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SEB CA). Patient demographic data, tumor measurements, treatment characteristics, and marginal recurrence rates were compiled and evaluated. RESULTS The mean numbers of cases identified per year for each tumor type were as follows: PDSCC, 6.19; DFSP, 2.44; MAC, 1.63; and EMPD, 0.63. For PDSCC, 85 cases were available for follow-up with a local recurrence rate of 6% at a mean follow-up time of 45 months. For DFSP, there were 35 cases with no local recurrence at a mean follow-up of 39 months. For MAC, there were 25 cases with a local recurrence rate of 12% at a mean follow-up of 39 months. For EMPD, there were 10 cases with no local recurrences at a mean follow-up of 34 months. CONCLUSIONS Collectively, our data on PDSCC, DFSP, MAC, and EMPD, combined with other studies in the literature, show that MMS is the most effective therapy for these rare aggressive cutaneous malignancies. [source] A frequency-domain formulation of MCE method for multi-axial random loadingsFATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 11 2008D. BENASCIUTTI ABSTRACT Many multi-axial fatigue limit criteria are formalized as a linear combination of a shear stress amplitude and a normal stress. To identify the shear stress amplitude, appropriate conventional definitions, as the minimum circumscribed circle (MCC) or ellipse (MCE) proposals, are in use. Despite computational improvements, deterministic algorithms implementing the MCC/MCE methods are exceptionally time-demanding when applied to "coiled" random loading paths resulting from in-service multi-axial loadings and they may also provide insufficiently robust and reliable results. It would be then preferable to characterize multi-axial random loadings by statistical re-formulations of the deterministic MCC/MCE methods. Following an early work of Pitoiset et al., this paper presents a statistical re-formulation for the MCE method. Numerical simulations are used to compare both statistical re-formulations with their deterministic counterparts. The observed general good trend, with some better performance of the statistical approach, confirms the validity, reliability and robustness of the proposed formulation. [source] Prevalence of de- O -acetylated serogroup C meningococci before the introduction of meningococcal serogroup C conjugate vaccines in the United KingdomFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2000Ray Borrow Abstract Meningococcal serogroup C conjugate (MCC) vaccines have been introduced in the UK to combat the rise in serogroup C meningococcal disease. Serogroup C meningococci may occur naturally expressing either O -acetylated (Oac+) or de- O -acetylated (Oac,) polysaccharide capsules. In a small study in the USA in the 1970s 15% of serogroup C meningococcal case isolates were reported to be Oac, though the prevalence of these Oac, isolates has not been recorded in the UK. This is of interest as the first MCC vaccines to be introduced are Oac+ and the potential impact of this on Oac, serogroup C isolates is unclear. Serogroup C isolates submitted to the Public Health Laboratory Service Meningococcal Reference Unit in January 1998 (n=113) and January 1999 (n=162) were investigated by dot blotting using monoclonals specific for Oac+ and Oac, serogroup C polysaccharides. This revealed 12% Oac, isolates for both January 1998 and January 1999. The proportion of fatal cases was found to similar for both Oac, and Oac+, 14 and 9% for 1998 and 5 and 3% for 1999, indicating that the pathogenic potential of these Oac, isolates is similar to Oac+. The acetylation status of serogroup C isolates needs to be monitored throughout and after the introduction of MCC vaccines. [source] Graft copolymerization modification of silk fabric with an organophosphorus flame retardantFIRE AND MATERIALS, Issue 5 2010Guan Jinping Abstract This paper mainly deals with flame retardance of a silk fabric treated with a vinyl phosphate dimethyl 2-(methacryloyloxyethyl) phosphate (DMMEP) onto silk fabric by a graft copolymerization technique. This paper also explores the relationship between limiting oxygen index (LOI) and weight gain of DMMEP treated silk fabric. The paper also investigates the whiteness, handle, tensile strength and laundering durability of treated silk fabric. Microscale combustion calorimetry (MCC) is applied to test the heat release rate of silk fabric. Thermal gravimetric analysis (TG) and differential thermal analysis (DTA) are carried out to investigate the thermal decomposition behavior of DMMEP treated silk fabric. The kinetic parameters, activation energy and pre-exponential factor are determined using the Kissenger method. Copyright © 2009 John Wiley & Sons, Ltd. [source] Transport of larval jack mackerel (Trachurus japonicus) estimated from trajectories of satellite-tracked drifters and advective velocity fields obtained from sequential satellite thermal images in the eastern East China SeaFISHERIES OCEANOGRAPHY, Issue 6 2002Hee-Yong Kim Abstract Transport processes of jack mackerel (Trachurus japonicus) larvae in the waters off the west coast of Kyushu in the eastern East China Sea, have been investigated using satellite-tracked surface drifters and consecutive satellite thermal images. Trajectories of drifters describe northward flows over the continental shelf, eastward flows of the Kuroshio south-west of Kyushu, and a weak clockwise gyre off the west coast of Kyushu. In particular, the clockwise gyre causes the entrainment of jack mackerel larvae into the waters off the west coast of Kyushu. Consecutive satellite thermal images help to elucidate the northward warm water intrusion from the Kuroshio front south-west of Kyushu. Particle trajectories using sea surface current fields computed with the Maximum Cross Correlation (MCC) technique also reveal that the transport of jack mackerel larvae into the nursery ground off the west coast of Kyushu caused by the anti-cyclonic gyre and the warm streamers are an important process for successful recruitment. [source] Ideas and Change in U.S. Foreign Aid: Inventing the Millennium Challenge CorporationFOREIGN POLICY ANALYSIS, Issue 2 2008Steven W. Hook Recent scholarship on foreign policy change focuses on the role of ideas in altering policies and related governing institutions. While a welcome antidote to the previous preoccupation with static analysis, this research has yet to provide adequate understanding of whether and how ideas produce change in specific instances. This study seeks to narrow this gap by examining a recent program change in U.S. foreign aid policy: the creation in 2004 of the Millennium Challenge Corporation (MCC), an independent agency designed to reward the world's most impoverished countries that had previously undertaken neoliberal economic reforms and democratic political reforms. The study identifies a convergence of widely shared principled and causal beliefs which, mediated through U.S. domestic structures, produced the most significant change in U.S. aid strategy and structures in nearly half a century. In melding societal theories that emphasize the role of transnational norm diffusion with theories of domestic politics, the study answers the call for multilevel explanations of foreign policy change. And by applying constructivist notions of ideas and discursive framing with rationalist conceptions of power and interests, the study further responds to the need for theoretical synthesis in the study of foreign policy. [source] Candidate-gene association studies with pedigree data: Controlling for environmental covariatesGENETIC EPIDEMIOLOGY, Issue 4 2003S.L. Slager Abstract Case-control studies provide an important epidemiological tool to evaluate candidate genes. There are many different study designs available. We focus on a more recently proposed design, which we call a multiplex case-control (MCC) design. This design compares allele frequencies between related cases, each of whom are sampled from multiplex families, and unrelated controls. Since within-family genotype correlations will exist, statistical methods will need to take this into account. Moreover, there is a need to develop methods to simultaneously control for potential confounders in the analysis. Generalized estimating equations (GEE) are one approach to analyze this type of data; however, this approach can have singularity problems when estimating the correlation matrix. To allow for modeling of other covariates, we extend our previously developed method to a more general model-based approach. Our proposed methods use the score statistic, derived from a composite likelihood. We propose three different approaches to estimate the variance of this statistic. Under random ascertainment of pedigrees, score tests have correct type I error rates; however, pedigrees are not randomly ascertained. Thus, through simulations, we test the validity and power of the score tests under different ascertainment schemes, and an illustration of our methods, applied to data from a prostate cancer study, is presented. We find that our robust score statistic has estimated type I error rates within the expected range for all situations we considered whereas the other two statistics have inflated type I error rates under nonrandom ascertainment schemes. We also find GEE to fail at least 5% of the time for each simulation configuration; at times, the failure rate reaches above 80%. In summary, our robust method may be the only current regression analysis method available for MCC data. Genet Epidemiol 24:273,283, 2003. © 2003 Wiley-Liss, Inc. [source] Colloidal-Crystal-Assisted Patterning of Crystalline MaterialsADVANCED MATERIALS, Issue 13 2010Cheng Li Abstract Colloidal crystals have shown great potential as versatile templates for the fabrication of patterned micro- and nanostructures with complex architectures and novel properties. The patterning of functional crystalline materials in two and three dimensions is essential to the realization of their applications in many technologically important fields. This article highlights some recent progress in the fabrication of 2D and 3D patterned crystalline materials with the assistance of colloidal crystals. By combining a bioinspired synthetic strategy based on a transient amorphous phase with a colloidal-crystal templating method, unique 3D ordered macroporous (3DOM) calcite single crystals can be created. Moreover, patterned arrays of regular ZnO nanopillars with controlled size, shape, and orientation can be fabricated via a facile wet chemical approach by using masks derived from monolayer colloidal crystals (MCC). [source] Two systems of resting state connectivity between the insula and cingulate cortexHUMAN BRAIN MAPPING, Issue 9 2009Keri S. Taylor Abstract The insula and cingulate cortices are implicated in emotional, homeostatic/allostatic, sensorimotor, and cognitive functions. Non-human primates have specific anatomical connections between sub-divisions of the insula and cingulate. Specifically, the anterior insula projects to the pregenual anterior cingulate cortex (pACC) and the anterior and posterior mid-cingulate cortex (aMCC and pMCC); the mid-posterior insula only projects to the posterior MCC (pMCC). In humans, functional neuroimaging studies implicate the anterior insula and pre/subgenual ACC in emotional processes, the mid-posterior insula with awareness and interoception, and the MCC with environmental monitoring, response selection, and skeletomotor body orientation. Here, we tested the hypothesis that distinct resting state functional connectivity could be identified between (1) the anterior insula and pACC/aMCC; and (2) the entire insula (anterior, middle, and posterior insula) and the pMCC. Functional connectivity was assessed from resting state fMRI scans in 19 healthy volunteers using seed regions of interest in the anterior, middle, and posterior insula. Highly correlated, low-frequency oscillations (< 0.05 Hz) were identified between specific insula and cingulate subdivisions. The anterior insula was shown to be functionally connected with the pACC/aMCC and the pMCC, while the mid/posterior insula was only connected with the pMCC. These data provide evidence for a resting state anterior insula,pACC/aMCC cingulate system that may integrate interoceptive information with emotional salience to form a subjective representation of the body; and another system that includes the entire insula and MCC, likely involved in environmental monitoring, response selection, and skeletomotor body orientation. Human Brain Mapp 2009. © 2008 Wiley-Liss, Inc. [source] Receptor architecture of human cingulate cortex: Evaluation of the four-region neurobiological modelHUMAN BRAIN MAPPING, Issue 8 2009Nicola Palomero-Gallagher Abstract The structural and functional organization of the human cingulate cortex is an ongoing focus; however, human imaging studies continue to use the century-old Brodmann concept of a two region cingulate cortex. Recently, a four-region neurobiological model was proposed based on structural, circuitry, and functional imaging observations. It encompasses the anterior cingulate, midcingulate, posterior cingulate, and retrosplenial cortices (ACC, MCC, PCC, and RSC, respectively). For the first time, this study performs multireceptor autoradiography of 15 neurotransmitter receptor ligands and multivariate statistics on human whole brain postmortem samples covering the entire cingulate cortex. We evaluated the validity of Brodmann's duality concept and of the four-region model using a hierarchical clustering analysis of receptor binding according to the degree of similarity of each area's receptor architecture. We could not find support for Brodmann's dual cingulate concept, because the anterior part of his area 24 has significantly higher AMPA, kainate, GABAB, benzodiazepine, and M3 but lower NMDA and GABAA binding site densities than the posterior part. The hierarchical clustering analysis distinguished ACC, MCC, PCC, and RSC as independent regions. The ACC has highest AMPA, kainate, ,2, 5-HT1A, and D1 but lowest GABAA densities. The MCC has lowest AMPA, kainate, ,2, and D1 densities. Area 25 in ACC is similar in receptor-architecture to MCC, particularly the NMDA, GABAA, GABAB, and M2 receptors. The PCC and RSC differ in the higher M1 and ,1 but lower M3 densities of PCC. Thus, multireceptor autoradiography supports the four-region neurobiological model of the cingulate cortex. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [source] Visual framework for development and use of constitutive modelsINTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 15 2002Youssef M. A. Hashash Abstract Advanced constitutive relations are used in geotechnical engineering to capture measured soil and rock behaviour in the laboratory, and in numerical models to represent the material response. These constitutive relations have traditionally been difficult to use, understand, and develop except by a limited number of specialists. This paper describes a framework for transforming the representation of constitutive relations, as well as stress and strain quantities from a series of mathematical equations and matrix quantities to multidimensional geometric/visual objects in a dynamic interactive colour-rich display environment. The paper proposes a shift in current approaches to the development of constitutive equations and their use in numerical simulations by taking advantage of rapid advancements in information technology and computer graphics. A novel interactive visualization development and learning environment for material constitutive relations referred to as VizCoRe is presented. Visualization examples of two constitutive relations, the linear elastic with von Mises failure criteria and the Modified Cam Clay (MCC) are shown. These include two- and three-dimensional renderings of stress states and paths and yield and failure surfaces. In addition, the environment allows for the visualization of the implicit integration algorithm used for the numerical integration of both constitutive models. Copyright © 2002 John Wiley & Sons, Ltd. [source] Application of ultrasonic waves in activation of microcrystalline celluloseJOURNAL OF APPLIED POLYMER SCIENCE, Issue 5 2008Xianling Wang Abstract In this work, microcrystalline cellulose (MCC) was activated with ultrasonic waves. The influences of ultrasonic treatment on the changes of supramolecular structures and morphology structure were studied by WAXS and SEM. The accessibility of the MCC was characterized by water retention value (WRV) and specific surficial area. The influence of ultrasonic treatment on the reactivity of MCC was investigated through the reaction of MCC being oxidized into 2,3-diadehyde cellulose (DAC) by periodate sodium. The mechanism of the reactivity change of ultrasonically treated MCC was examined. The results showed that the degree of crystallinity of MCC decreased and the degree of polymerization showed little change after treatment with ultrasonic waves. The morphologial variation of the treated MCC was significant when compared with the untreated MCC, which contribute to the improvement of accessibility. The aldehyde content of DAC prepared from ultrasonically treated MCC was improved from 64.19 to 85.00%, indicating that the regioselective oxidation reactivity of MCC was significantly improved. The aldehyde content was found to first increase with time of ultrasonic treatment to a point, and then decrease as time progressed. In addition, the aldehyde content was found to increase with an increase in ultrasonic power. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Elastofibromatous change of the oral mucosa: case report and literature reviewJOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2010Cassiano Francisco Weege Nonaka Elastofibroma is an uncommon fibrous pseudotumor that usually occurs in the subscapular region of middle-aged and older adults. Since its seminal description, cases of elastofibroma or elastofibroma-like proliferations have been identified at several anatomic locations, including the foot, hand, thigh, olecranon, gastrointestinal tract, trachea, dorsal spine and eye. Involvement of the oral cavity is rare, with only four cases reported to date. Herein, we report a case of elastofibromatous change in the soft palate of a 55-year-old man and review the literature regarding pathogenesis, clinicopathologic features, differential diagnosis and management. Nonaka CFW, Ręgo DM, Miguel MCC, de Souza LB, Pinto LP. Elastofibromatous change of the oral mucosa: case report and literature review. [source] Bif-1 and Bax expression in cutaneous Merkel cell carcinomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2009Scott M. Schlauder Background:, Bax-interacting factor-1 (Bif-1) binds to Bax, which in turn activates this proapoptotic protein. In the absence of Bif-1, the ability to induce apoptosis through the intrinsic pathway is greatly reduced. Merkel cell carcinoma (MCC) classically shows an aggressive behavior and lack of response to chemotherapy, which remains unexplained. Previous studies have documented the presence of Bax in MCC, but Bif-1 expression has not been evaluated. Herein, the expression of Bif-1 and Bax in cutaneous MCC is examined. Materials and methods:, The immunohistochemical expression of Bif-1 and Bax protein was examined in nine cases of MCC. Both positive and negative controls were conducted. All the cases were reviewed by a single dermatopathologist. Results:, Bif-1 was detected in nine cases (100%), and Bax was expressed in six cases (66%). The percent positive cells for Bif-1 in MCC ranged from 85% to 98% positive (mean 93.9%). At the same time, decreased Bax expression was shown with 0,8% positive cells (mean 3.45%). Conclusion:, The increased expression of Bif-1 in MCC is associated with low levels of Bax staining. These findings suggest that the upregulation of Bif-1 could in part be responsible for tumorigenesis in cutaneous MCC. As shown, Bax and Bif-1 expression are not exclusively antithetical; therefore, future studies evaluating the expression of both proteins should be conducted. [source] Expression of HuR in Merkel cell carcinoma and in normal skinJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2008Virve Koljonen Background:, HuR is a ubiquitously expressed member of the Elav/Hu family of mRNA-binding proteins, and its cytoplasmic expression has been recognised to participate in carcinogenesis. The aims of this study were to explore the expression pattern of HuR in primary Merkel cell carcinoma (MCC), lymph node metastases and non-neoplastic skin. Methods:, Twenty-two primary MCC samples and five lymph node metastases were evaluated for HuR expression by immunohistochemistry. The data were compared with clinical parameters. Results:, Nuclear and cytoplasmic HuR-staining patterns were observed. Nuclear immunoreactivity was observed in 91% of the primary tumors and in 80% of the lymph node metastases. Cytoplasm was positive in 27% of the primary tumors and in 60% of the lymph node metastases. No cytoplasmic HuR immunoreactivity was detected in non-neoplastic skin. However, moderate to strong nuclear staining was found in normal epidermis and in the epithelium of hair follicles and sebaceous glands. Expression of HuR in MCC did not associate with clinicopathological parameters. Conclusions:, Primary MCCs and their lymph node metastases as well as non-neoplastic skin show nuclear expression of HuR protein. In contrast to non-neoplastic skin, a subset of MCC tumors show cytoplasmic HuR staining, which may contribute to carcinogenesis in MCC. [source] Metastatic Basal Cell Carcinoma with Neuroendocrine Differentiation or Merkel Cell Carcinoma?JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005A. Andea We present here a case of basal cell carcinoma (BCC) with neuroendocrine features that has transformed into a high-grade neuroendocrine carcinoma with various morphologic features of Merkel cell carcinoma (MCC). A 54-year-old white female was treated for a BCC of the right thigh. Pathologic examination revealed an otherwise classical BCC that demonstrated granular positivity for chromogranin. Six years later the patient developed a right inguinal lymphadenopathy diagnosed as metastatic BCC with squamous changes. The metastatic BCC showed partial peripheral palisading and a trabecular pattern. Two years later the patient underwent a right nephrectomy due to obstruction of the right ureter by metastatic BCC. After another four years the patient came back with extensive involvement of the appendiceal wall and right ovary by a diffusely infiltrating metastatic basaloid and trabecular carcinoma. This time the tumor had many histologic features of MCC and showed strong positivity for chromogranin and also for CK20 and NSE. Electron microscopy revealed neurosecretory granules. This case is an example of a chromogranin positive basal cell carcinoma of the skin, which transformed during multiple recurrences into a high grade neuroendocrine carcinoma with features of Merkel cell tumor, demonstrating the potential for cross differentiation among skin tumors. [source] Merkel cell carcinoma: a clinicopathologic study with prognostic implicationsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2004Ryan T. Mott Background:, Merkel cell carcinoma (MCC) is a frequently aggressive neuroendocrine malignancy of the skin that presents in sun-exposed areas on elderly patients. Although originally described over 30 years ago, many aspects of MCC remain to be defined. Of particular importance is the need to identify prognostic factors capable of predicting the biological behavior of these tumors. Knowledge of these factors may help in determining which patients require more aggressive treatment regimens. In this study, we examined 25 cases of MCC with an attempt to identify clinical, histopathological, or immunohistochemical features capable of predicting disease outcome. Methods:, Features that we evaluated in each case included age, gender, race, tumor location, tumor size, depth of invasion, growth pattern, lymphocytic infiltration, mitotic activity, ulceration, necrosis, vascular invasion, and perineural invasion. In addition, we examined neural cell adhesion molecule and cytokeratin-20 expression using immunohistochemical methods. Results:, We found that most patients were males (84%) with an average age of 74 years. The tumors were located on the head and neck (68%) and upper extremities (32%). Overall, 64% of the patients developed metastatic disease to regional lymph nodes or distant sites (average follow-up time of 21 months). Local recurrence was also common, occurring in 29% of the patients. The overall 1- and 2-year survival rates were 80 and 53%, respectively. Histopathological examination revealed tumors with an average size of 7.2 mm. Common features included invasion into the subcutaneous adipose tissue, solid growth pattern, tumor necrosis, and vascular and perineural invasion. Findings that had a statistically significant correlation with poor outcome included tumor size ,5 mm (p = 0.047), invasion into the subcutaneous adipose tissue (p = 0.005), diffuse growth pattern (p = 0.040), and heavy lymphocytic infiltration (p = 0.017). The remaining findings, including the immunohistochemical results, did not correlate with disease outcome. Using logistic regression models, we show that depth of invasion and degree of lymphocytic infiltration are strong predictors of disease outcome. Conclusions:, The current controversies regarding the treatment of early-stage MCC (i.e., localized disease) underscore the importance of identifying clinicopathological features capable of predicting tumor behavior. In this study, we have identified several prognostic features in MCC. Perhaps, these features may prove useful in identifying patients who require more aggressive treatment regimens. [source] Ets-1 immunohistochemical expression in non-melanoma skin carcinomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2004Connie A. Keehn Background:, Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in non-melanoma skin carcinomas. Design:, A series of 26 primary cutaneous skin lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle Upon Tyne, England, UK) was scored by an average of the mean labeling intensity (MLI), where no nuclear staining = 0, weak nuclear staining = 1, moderate nuclear staining = 2, and strong nuclear staining = 3. Results:, All basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC) cases exhibited negative nuclear staining, for an average MLI of 0. Keratoacanthomas, squamous cell carcinoma in situ (SIS), and well-differentiated squamous cell carcinomas (SCCs) exhibited negative to weak nuclear staining, for an average MLI of 0.4 ± 0.3. Moderately differentiated SCCs exhibited moderate nuclear staining, for an average MLI of 1.8 ± 0.6. Poorly differentiated SCCs and metastatic SCCs exhibited very strong nuclear staining, with an average MLI of 2.8 ± 0.2. Conclusions:, Ets-1 is not expressed in cutaneous BCC or MCC and is weakly expressed in SIS and forms of well-differentiated SCC. Although the intensity of Ets-1 immunostaining distinguished between well-differentiated and poorly differentiated SCC (p < 0.0001), it failed to discriminate between in situ and well-differentiated SCCs. The preliminary data suggests Ets-1 may be important in the pathogenesis of invasive SCC. [source] Loss of heterozygosity at APC and MCC genes of oral cancer and leukoplakia tissues from Indian tobacco chewersJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2003Nilabja Sikdar Abstract Background:, Loss of heterozygosity (LOH) at tumor suppressor genes, such as adenomatous polyposis coli (APC) and mutated in colon cancer (MCC) genes, is one of the early events in carcinogenesis of oral tissue in Caucasian and Chinese patients. We wanted to check whether it is also true in Indian oral pre-cancer and cancer patients. Methods:, Loss of heterozygosity at APC and MCC genes was investigated in 57 and 40 unrelated primary oral leukoplakia (a pre-cancerous lesion) and squamous cell carcinomas (SCC), respectively, by polymerase chain reaction. Results:, In these samples, most of the leukoplakia patients had tobacco smoking habit whereas majority of cancer patients had tobacco chewing habit. LOH at APC gene was observed in 4 of 16 (25%) and 1 of 29 (3%) informative tumor and leukoplakia DNAs from tobacco chewers, respectively. LOH at MCC gene was not detected either in tumor or in leukoplakia DNAs. Conclusion:, This infrequent LOH at APC gene of pre-cancer and cancer tissues suggests that it may not be an early event in oral carcinogenesis in these patients. [source] The rheological properties of modified microcrystalline cellulose containing high levels of model drugsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2009Paul E. Knight Abstract The rheological properties of different types of microcrystalline cellulose (MCC) mixed with model drugs and water have been evaluated to identify the influence of sodium carboxymethylcellulose (SCMC) added to the cellulose during preparation. A ram extruder was used as a capillary rheometer. The mixtures consisted of 20% spheronizing agent (standard grade MCC or modified types with 6% or 8% of low viscosity grade SCMC) and 80% of ascorbic acid, ibuprofen or lactose monohydrate. The introduction of SCMC changed all rheological parameters assessed. It produced more rigid systems, requiring more stress to induce and maintain flow. Degree of non-Newtonian flow, angle of convergence, extensional viscosity, yield and die land shear stress at zero velocity, and static wall friction were increased, but recoverable shear and compliance were decreased. The presence of SCMC did not remove the influence of the type of drug. The mixture of ibuprofen and standard MCC had the lowest values for shear stress as a function of the rate of shear, extensional viscosity, and angle of convergence, but the highest values for recoverable shear and compliance. The findings indicate that the system has insufficient rigidity to form pellets. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2160,2169, 2009 [source] Combined effects of wetting, drying, and microcrystalline cellulose type on the mechanical strength and disintegration of pelletsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2009Maria Balaxi Abstract Effects of wetting and drying conditions on micromeritic, mechanical and disintegration properties of microcrystalline cellulose (MCC) pellets were evaluated. Extrusion/spheronization and three drying methods (fluidized bed, microwaves, and freeze drying) were applied using two wetting liquids (water or water-isopropanol 60:40 w/w) and three MCC types: (standard, silicified, and modified). Additionally, the effects of drying method were compared on highly porous pellets prepared by the incorporation and extraction of pore former (NaCl). It was found that the drying method has the greatest effect on the pellet size and porosity followed by the wetting liquid. The modification of MCC resulted in reduced water retention ability, implying hornification, increased porosity, reduced resistance to deformation and tensile strength of pellets. The disintegration time also decreased markedly due to the modification but only in the low porosity range <37%. Silicification increased greatly the disintegration time of the low porosity pellets (<14%). Combination of water-isopropanol, freeze drying and modified MCC gave the greatest increase in pellet size and porosity. The increase in pellet porosity caused exponential reduction in the resistance to deformation, tensile strength and disintegration time, as expected. Compared to fluidized bed, the freeze drying resulted in 20,30% higher porosity for pellets prepared without pore former and 6% for those with pore former, indicating the possibility of preparing highly porous pellets by employing freeze drying. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:676,689, 2009 [source] Quantifying effects of particulate properties on powder flow properties using a ring shear testerJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2008Hao Hou Abstract Effects of particle size, morphology, particle density, and surface silicification, on powder flow properties were investigated using a ring shear tester. Flow properties were quantified by flow function (FF), that is, unconfined yield strength, fc, as a function of major principal stress. A total of 11 powders from three series of microcrystalline cellulose (MCC): Avicel (regular MCC, elongated particles), Prosolv (silicified MCC, elongated particles), and Celphere (spherical MCC), were studied. Particle size distribution in each type of MCC was systematically different. Within each series, smaller particles always led to poorer powder flow properties. The slope of FF line was correlated to degree of powder consolidation by external stress. A key mechanism of the detrimental effect of particle size reduction on flow properties was the larger powder specific surface area. Flow properties of Celphere were significantly better than Avicel of comparable particles size, suggesting spherical morphology promoted better powder flow properties. Flow properties of powders different in densities but similar in particle size, shape, and surface properties were similar. When corrected for density effect, higher particle density corresponded to better flow behavior. Surface silicification significantly improved flow properties of finer MCC, but did not improve those of coarser. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4030,4039, 2008 [source] Use of chitosan-alginate as alternative pelletization aid to microcrystalline cellulose in extrusion/spheronizationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2007Nattawut Charoenthai Abstract Two types of different molecular weight chitosan were investigated as a pelletization aid in extrusion/spheronization using water as granulation liquid. Spherical pellets with a maximum fraction of 60% w/w chitosan could be produced when 1.25,2.5% w/w sodium alginate was included in the formulations with no microcrystalline cellulose (MCC). Chitosan with lower molecular weight of 190 kDa showed a better pellet forming property. The pellets obtained had acceptable physical characteristics and a fast drug release. The results from Fourier transform infrared spectroscopy, differential scanning calorimetry and 13C CP-MAS nuclear magnetic resonance spectroscopy confirmed the formation of polyelectrolyte complex (PEC) between chitosan and sodium alginate, which might be a reason for successful pelletization by extrusion/spheronization. Moreover, the presence of PEC might influence the physical characteristics and dissolution behavior of chitosan-alginate pellets. The results indicated an achievement in production of pellets by extrusion/spheronization without using MCC. Moreover, chitosan combined with sodium alginate could be used as a promising alternative pelletization aid to MCC in extrusion/spheronization. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2469,2484, 2007 [source] A novel method for deriving true density of pharmaceutical solids including hydrates and water-containing powdersJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2004Changquan (Calvin) Sun Abstract True density is commonly measured using helium pycnometry. However, most water-containing powders, for example, hydrates, amorphous drugs and excipients, and most tablet formulations, release water when exposed to a dry helium atmosphere. Because released water brings significant errors to the measured true density and drying alters the nature of water-containing solids, the helium pycnometry is not suitable for those substances. To overcome this problem, a novel method has been developed to accurately calculate powder true density from compaction data. No drying treatment of powder samples is required. Consequently, the true density thus obtained is relevant to tableting characterization studies because no alteration to the solid is induced by drying. This method involves nonlinear regression of compaction pressure-tablet density data based on a modified Heckel equation. When true density values of water-free powders derived by this novel method were plotted against values measured using pycnometry, a regression line with slope close to unity and intercept close to zero was obtained. Thus, the validity of this method was supported. Using this new method, it was further demonstrated that helium pycnometry always overestimates true densities of water containing powders, for example, hydrates, microcrystalline cellulose (MCC), and tablet formulations. The calculated true densities of powders were the same for different particle shapes and sizes of each material. This further suggests that true density values calculated using this novel method are characteristic of given materials and independent of particulate properties. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:646,653, 2004 [source] The change in characteristics of microcrystalline cellulose during wet granulation using a high-shear mixerJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2001Tatsuya Suzuki The objective of this study was to investigate the mechanism of hard granule formation and to demonstrate the applicability of X-ray diffraction methods for studying the polymeric pharmaceutical excipients. Using a high-shear mixer, microcrystalline cellulose (MCC) was granulated with water as the granulating liquid. The hardness of the MCC granules increased with granulation time and the amount of water added. The specific surface area measured by the N2 adsorption method was reduced during the process. Crystallite size of cellulose, calculated by Scherrer's equation adapted for wide angle X-ray diffraction method, decreased with granulation time and with increasing amounts of water added. Debye plots for X-ray small scattering patterns suggested that the average magnitude of the continuous solid region in MCC granules became significantly greater, whereas the specific surface area of the MCC granules, calculated from Debye plots, became smaller in comparison with that of intact MCC. These findings suggested that the long-chain structures in MCC were disrupted, resulting in smaller units with shorter chain lengths due to the strong shear force of the impeller. These smaller units then form a network within the granules. Thus, MCC granules are strengthened with longer granulation time and greater amounts of water, resulting in a more intricate network. The change in MCC chain length and physical structure can be experimentally detected using the small-angle X-ray scattering and wide-angle powder X-ray diffraction methods. [source] Microwave-assisted derivatization of cellulose in an ionic liquid: An efficient, expedient synthesis of simple and mixed carboxylic estersJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 1 2010Shirley Possidonio Abstract Microwave (MW)-assisted cellulose dissolution in ionic liquids (ILs) has routinely led either to incomplete biopolymer solubilization, or its degradation. We show that these problems can be avoided by use of low-energy MW heating, coupled with efficient stirring. Dissolution of microcrystalline cellulose in the IL 1-allyl-3-methylimidazolium chloride has been achieved without changing its degree of polymerization; regenerated cellulose showed pronounced changes in its index of crystallinity, surface area, and morphology. MW-assisted functionalization of MCC by ethanoic, propanoic, butanoic, pentanoic, and hexanoic anhydrides has been studied. Compared with conventional heating, MW irradiation has resulted in considerable decrease in dissolution and reaction times. The value of the degree of substitution (DS) was found to be DSethanoate > DSpropanoate > DSbutanoate. The values of DSpentanoate and DShexanoate were found to be slightly higher than DSethanoate. This surprising dependence on the chain length of the acylating agent has been reported before, but not rationalized. On the basis of the rate constants and activation parameters of the hydrolysis of ethanoic, butanoic, and hexanoic anhydrides in aqueous acetonitrile (a model acyl transfer reaction), we suggest that this result may be attributed to the balance between two opposing effects, namely, steric crowding and (cooperative) hydrophobic interactions between the anhydride and the cellulosic surface, whose lipophilicity has increased, due to its partial acylation. Four ethanoate-based mixed esters were synthesized by the reaction with a mixture of the two anhydrides; the ethanoate moiety predominated in all products. The DS is reproducible and the IL is easily recycled. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 48: 134,143, 2010 [source] Expression of minichromosome maintenance proteins in Merkel cell carcinomaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2009T Gambichler Abstract Objective, Minichromosome maintenance (MCM) nuclear proteins have barely been employed in the diagnosis of skin malignancies. We aimed to assess whether MCM immunohistochemistry can be utilized to examine tumour proliferation in Merkel cell carcinoma (MCC). Methods, In this pilot study, we studied skin specimens of eight patients with MCC. As a control, eight patients with cutaneous malignant melanoma (MM) were included. Immunohistochemistry was performed for MCM4, MCM6, MCM7, Ki-67, p53, and p21. Results, Protein expression of MCM4 (66.0 ± 26.5% vs. 33.9 ± 22.4%; P = 0.017), MCM6 (70.9 ± 11.9 vs. 31.7 ± 22.7; P = 0.0031), and MCM7 (76.5 ± 16.4% vs. 34.9 ± 25.5%; P = 0.0013) was significantly increased in tumour cells of MCC when compared to tumour cells of MM. Ki-67 immunoreactivity was also significantly higher in MCC than in MM (28.7 ± 7.9 vs. 11.0 ± 9.2; P = 0.0012). Immunolabelling of p53 (68.6 ± 26.2 vs. 58.4 ± 28.8; P = 0.46) and p21 (40.1 ± 38.8 vs. 25.8 ± 16.1; P = 0.35) was relatively high but not significantly increased in MCC when compared to MM. Conclusion, Our preliminary data indicate that MCM immunohistochemistry may be a useful tool for the determination of tumour cell proliferation in MCC. [source] Differential kinetic features by tumour topography in cutaneous small-cell neuroendocrine (Merkel cell) carcinomasJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 9 2007L Pozo Abstract Background/Objectives Merkel cell carcinomas (MCC) reveal epithelial and neuroendocrine differentiation, but its topographic cell kinetics remains unknown. This study analyses proliferation, apoptosis, and DNA ploidy by topography, features that can help planning therapeutic protocols. This study topographically analyses proliferation, apoptosis, and DNA ploidy. Methods We selected 27 small-cell MCCs (expressing one epithelial and two neural markers, with consistent ultrastructural findings) to evaluate mitotic figure counting, Ki-67 index, apoptosis index based on the in situ end labelling of fragmented DNA (using Escherichia coli DNA polymerase I, Klenow fragment), DNA ploidy, and BCL2 and TP53 immuno-expression. At least 50 high-power fields were screened per topographic compartment (superficial or papillary dermis, and deep or reticular dermis), recording average and standard deviation for each variable. Variables were statistically compared in each tumour compartment using analysis of variance and Student's t -test (significant if P < 0.05). Results MCCs revealed superficial aneuploid DNA content, and no topographic differences for proliferation markers. Apoptosis showed significantly lower values in the deep compartment (average, P = 0.0050, and standard deviation, P = 0.0074), correlating with increased BCL2 and TP53 immuno-expressions. Conclusions High homogeneously distributed proliferation and superficial aneuploid DNA content defines MCCs. Apoptosis follows proliferation in superficial compartments, being less variable and proliferation independent in deep compartments, where it is inversely correlated with BCL2/TP53 expression. [source] Merkel cell carcinoma: a clinicopathological study of 11 casesJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2005E Acebo ABSTRACT Objective, To report our 12-year experience with Merkel cell carcinomas (MCCs) from a clinical and pathological point of view. Subjects and setting, Eleven MCCs were diagnosed at our institution between 1991 and 2002. Methods, A retrospective clinical, histopathological and immunohistochemical study was performed. Age, gender, location, size, stage, treatment and follow-up data were collected. Histopathological pattern and immunohistochemical study with CAM 5.2, cytokeratin 20 (CK20), CK7, Ber EP4, neurofilaments, synaptophysin, chromogranin, S100 protein, p53 protein, CD117, leucocyte common antigen (LCA) and Ki-67 were accomplished. Results, Six females and five males with a mean age of 82 years were identified. Tumours were located on the face (n = 6), extremities (n = 3) and trunk (n = 1). At diagnosis, one patient was in stage Ia, six in stage Ib, three in stage II and one in stage III. All but one patient experienced wide surgical excision of the tumour. Additional treatment consisted of lymph node dissection in two patients, radiotherapy in four patients and systemic chemotherapy in one patient. Local recurrence developed in five patients. Three patients died because of MCC after 14 months of follow-up. Intermediate-size round cell proliferation was found in all cases. Additional small-size cell pattern and trabecular pattern were observed in seven and six cases, respectively. Eccrine and squamous cell differentiation were found in three cases. A dot-like paranuclear pattern was observed in all cases with CAM 5.2 and neurofilaments, and in 89% of cases with CK20. Seventy-five per cent of cases reacted with Ber EP4, chromogranin and synaptophysin, 70% with p53, 22% with S100 protein, 55% with CD117 and none with LCA. Ki-67 was found in 75% of tumoral cells on average. Fifty per cent of MCCs reacted with CK7 and showed eccrine differentiation areas. Conclusions, MCC is an aggressive neuroendocrine tumour of the elderly. Wide surgical excision is the recommended treatment. Lymph node dissection, adjuvant radiotherapy and chemotherapy decrease regional recurrences but have not been demonstrated to increase survival. Immunohistochemically, MCC is an epithelial tumour with neuroendocrine features. [source] | ||||||||||||||||||||||