Regulation of the Melanoma Cell Adhesion Molecule Gene in Melanoma: Modulation of mRNA Synthesis by Cyclic Adenosine Monophosphate, Phorbol Ester, and Stem Cell Factor/c-Kit Signaling

The melanoma cell adhesion molecule was identified as a human melanoma-associated antigen that increases in expression as tumors increase in thickness and begin to acquire metastatic potential. Clinical and experimental evidences suggest that the development of metastatic capacity might be the consequence of increased melanoma cell adhesion molecule expression. The mechanisms for upregulation of the melanoma cell adhesion molecule during melanoma progression are, however, still poorly understood. In this study, we show that melanoma cell adhesion molecule expression is tightly regulated at the transcriptional level. Using a combination of CAT reporter assays and semiquantitative reverse transcriptase–polymerase chain reaction, we observed that cyclic adenosine monophosphate significantly increases transcription of the melanoma cell adhesion molecule in nonmetastatic melanoma cells. In metastatic cells, transcription of the gene was constitutive and could not be further increased by cyclic adenosine monophosphate. On the other hand, melanoma cell adhesion molecule promoter activity was impeded upon treatment with phorbol esters or in the presence of stem cell factor, a phenomenon which was protein kinase C-dependent. Promoter-deletion studies demonstrated that the first 196 nt of the melanoma cell adhesion molecule promoter region are sufficient to get full expression in metastatic melanoma cells. This fragment contains five binding sites for the transcription factor Sp1 and DNA mobility shift experiments showed direct binding of Sp1 to the promoter. In conclusion, our results indicate that Sp1 is sufficient to drive constitutive melanoma cell adhesion molecule expression in metastatic melanoma cells. In nonmetastatic cells, however, melanoma cell adhesion molecule expression is repressed and we speculate that stem cell factor/c-Kit signaling might be responsible for the control of melanoma cell adhesion molecule synthesis, and thus, perhaps, of melanoma progression and metastasis

Actinic keratoses - a systemic review

Mainly elderly people with pale skin are affected by actinic keratoses (AK). Due to the demographic change, the prevalence of AK increased over the last years. An established risk factor is chronic UV-exposure (outdoor workers) inducing mutations of the tumor suppressor gene TP53 and the oncogene H-Ras. This leads to an intraepidermal proliferation of atypical keratinocytes. The term “field cancerization” characterises the presentation of multiple AK in UV-exposed areas. AK are also termed squamous cell carcinoma (SCC) in situ. The risk for AK turning into a SCC is 6-10%. In order to avoid invasive growth, an early treatment is recommended. During the last years multiple therapeutic options have been established. Depending on the clinical extent, lesion- or field-directed therapies with excellent clinical response and cosmetic results are available

Актинический кератоз - обзор литературы

Mainly elderly people with pale skin are affected by actinic keratoses (AK). Due to the demographic change, the prevalence of AK increased over the last years. An established risk factor is chronic UV-exposure (outdoor workers) inducing mutations of the tumor suppressor gene TP53 and the oncogene H-Ras. This leads to an intraepidermal proliferation of atypical keratinocytes. The term field cancerization characterises the presentation of multiple AK in UV-exposed areas. AK are also termed squamous cell carcinoma (SCC) in situ. The risk for AK turning into a SCC is 6-10%. In order to avoid invasive growth, an early treatment is recommended. During the last years multiple therapeutic options have been established. Depending on the clinical extent, lesion- or field-directed therapies with excellent clinical response and cosmetic results are available.Актиническому кератозу (АК) в основном подвержены пожилые люди со светлой кожей. За последние годы в связи с демографическими изменениями увеличилась распространенность АК. установленным фактором риска, приводящим к возникновению мутаций в антионкогене TP53 и онкогене H-Ras, является хроническое ультрафиолетовое воздействие (работа на открытом воздухе), которое способствует внутриэпидермальной пролиферации атипичных кератиноцитов. термин поле канцеризации характеризуется наличием множественного АК в участках, подверженных УФ-облучению. также АК называется преинвазивной плоскоклеточной карциномой или плоскоклеточной карциномой in situ. Риск превращения АК в плоскоклеточную карциному составляет 6-10%. Во избежание инвазивного роста рекомендуется лечение на ранних стадиях. За последние годы были разработаны различные варианты терапевтического лечения. В зависимости от степени выраженности признаков существуют методы терапии, направленные на поврежденные участки и дающие превосходные косметические и клинические результаты

Stability and Representation Dependence of the Quantum Skyrmion

A constructive realization of Skyrme's conjecture that an effective pion mass ``may arise as a self consistent quantal effect'' based on an ab initio quantum treatment of the Skyrme model is presented. In this quantum mechanical Skyrme model the spectrum of states with $I=J$, which appears in the collective quantization, terminates without any infinite tower of unphysical states. The termination point depends on the model parameters and the dimension of the SU(2) representation. Representations, in which the nucleon and $\Delta_{33}$ resonance are the only stable states, exist. The model is developed for both irreducible and reducible representations of general dimension. States with spin larger than 1/2 are shown to be deformed. The representation dependence of the baryon observables is illustrated numerically.Comment: 19 pages, Late

Access to health care for persons with disabilities in rural South Africa

BACKGROUND: Global research suggests that persons with disabilities face barriers when accessing health care services. Yet, information regarding the nature of these barriers, especially in low-income and middle-income countries is sparse. Rural contexts in these countries may present greater barriers than urban contexts, but little is known about access issues in such contexts. There is a paucity of research in South Africa looking at "triple vulnerability" - poverty, disability and rurality. This study explored issues of access to health care for persons with disabilities in an impoverished rural area in South Africa. METHODS: The study includes a quantitative survey with interviews with 773 participants in 527 households. Comparisons in terms of access to health care between persons with disabilities and persons with no disabilities were explored. The approach to data analysis included quantitative data analysis using descriptive and inferential statistics. Frequency and cross tabulation, comparing and contrasting the frequency of different phenomena between persons with disabilities and persons with no disabilities, were used. Chi-square tests and Analysis of Variance tests were then incorporated into the analysis. RESULTS: Persons with disabilities have a higher rate of unmet health needs as compared to non-disabled. In rural Madwaleni in South Africa, persons with disabilities faced significantly more barriers to accessing health care compared to persons without disabilities. Barriers increased with disability severity and was reduced with increasing level of education, living in a household without disabled members and with age. CONCLUSIONS: This study has shown that access to health care in a rural area in South Africa for persons with disabilities is more of an issue than for persons without disabilities in that they face more barriers. Implications are that we need to look beyond the medical issues of disability and address social and inclusion issues as well

Withdrawn, strong, kind, but de-gendered: Non-disabled South Africans’ stereotypes concerning persons with physical disabilities

The present paper examines stereotyping in relation to physical disability and gender in the South Africa. Cross-sectional data for the present study were gathered using free response items in a large survey (n = 1990) examining the attitudes of people without disability towards different facetsof sexuality and disability. The most prominent stereotypes found in thepresent study were those which characterised PWPD as withdrawn and shy, SuperCrips, or happy, funny, and kind. The findings in the present papersuggest that stereotypes of PWPD are not overwhelmingly de-sexualising, but are undifferentiated by gender

Intercomparison of four different in-situ techniques for ambient formaldehyde measurements in urban air

International audienceResults from an intercomparison of several currently used in-situ techniques for the measurement of atmospheric formaldehyde (CH2O) are presented. The measurements were carried out at Bresso, an urban site in the periphery of Milan (Italy) as part of the FORMAT-I field campaign. Eight instruments were employed by six independent research groups using four different techniques: Differential Optical Absorption Spectroscopy (DOAS), Fourier Transform Infra Red (FTIR) interferometry, the fluorimetric Hantzsch reaction technique (five instruments) and a chromatographic technique employing C18-DNPH-cartridges (2,4-dinitrophenylhydrazine). White type multi-reflection systems were employed for the optical techniques in order to avoid spatial CH2O gradients and ensure the sampling of nearly the same air mass by all instruments. Between 23 and 31 July 2002, up to 13 ppbv of CH2O were observed. The concentrations lay well above the detection limits of all instruments. The formaldehyde concentrations determined with DOAS, FTIR and the Hantzsch instruments were found to agree within ±11%, with the exception of one Hantzsch instrument, which gave systematically higher values. The two hour integrated samples by DNPH yielded up to 25% lower concentrations than the data of the continuously measuring instruments averaged over the same time period. The consistency between the DOAS and the Hantzsch method was better than during previous intercomparisons in ambient air with slopes of the regression line not significantly differing from one. The differences between the individual Hantzsch instruments could be attributed in part to the calibration standards used. Possible systematic errors of the methods are discussed

The record large 2006 Antarctic ozone hole

Póster presentado en: EGU General Assembly 2007 celebrada del 15 al 20 de abril en Viena, Austria.The Antarctic ozone hole of 2006 was unusually large. Several parameters used to measure the extent of ozone destruction and ozone hole severity set new records in 2006. Several ground-based stations measured record low total ozone column amounts. Ozonesonde measurements also revealed in many cases record low values of ozone in certain height intervals. The dynamics of the 2006 ozone hole will be described together with satellite-based measurements and calculations of ozone hole area and mass deficit. These finding will be supplemented with several examples of data from various stations in Antarctica

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes