Telomerase activity in the vaginal margins of radical hysterectomy in patients with carcinoma of the cervix: Correlation with histology and human papillomavirus

This study was undertaken to evaluate the telomerase activity both in the tumor and in the vaginal margins of radical hysterectomy in patients with squamous cell carcinoma (SCC) of the cervix. Thirty-three patients with SCC of the cervix (study group) and 13 patients with uterine myoma (control group) were prospectively studied. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM). The specimens were analyzed by histopathology, by a telomerase PCR-TRAP-ELISA kit, and by polymerase chain reaction using human papillomavirus (HPV) DNA. The telomerase activity was significantly higher in the tumor than in the benign cervix (P < 0.001). There was no difference in telomerase activity in the AVM and PVM in patients with cervical carcinoma compared to the control group. Telomerase activity was associated with the presence of histologic malignancy in the PVM of patients submitted to radical hysterectomy (P = 0.03). This association was not observed with the presence of HPV in AVM or PVM in the study group. Telomerase activity is a marker of histologic malignancy in patients with SCC of the cervix. There was no association between the telomerase activity and the presence of HPV in vaginal margins of patients submitted to radical hysterectomy. © 2006, Copyright the Authors.

Human papillomavirus and Epstein-Barr virus infection, p53 expression, and cellular proliferation in laryngeal carcinoma

Laryngeal carcinomas are aggressive neoplasms with controversial association with the human papillomavirus (HPV) and Epstein-Barr virus (EBV). So far, the impairment of p53 protein function and its impact on cellular proliferation has not been studied adequately in these tumors. In this work, molecular biologic techniques were used to assess the frequency of HPV and EBV in 110 squamous cell carcinomas of the larynx. In addition, accumulation of p53 and Ki-67 cell proliferation antigen expression in malignant cells was assessed by immunohistochemical analysis. High-grade HPV was found in 37.3% of cases, and none had demonstrable EBV infection. Accumulation of p53 was found in 78.2% of the cases, and it was related to a high Ki-67 labeling index and higher histologic grade. The results demonstrate association of HPV with more than one third of laryngeal carcinomas studied, mainly glottic tumors. Tumors with increased cell proliferation were more frequently high grade, with p53 accumulation and lymph node metastasis. © American Society for Clinical Pathology.

Overexpression of ANXA1 in Penile Carcinomas Positive for High-Risk HPVs

The incidence of penile cancer varies between populations but is rare in developed nations. Penile cancer is associated with a number of established risk factors and associated diseases including phimosis with chronic inflammation, human papillomavirus (HPV) infection, poor hygiene and smoking. The objective of this study was to identify genes related to this type of cancer. The detection of HPV was analyzed in 47 penile squamous cell carcinoma samples. HPV DNA was detected in 48.9% of penile squamous cell carcinoma cases. High-risk HPV were present in 42.5% of cases and low-risk HPV were detected in 10.6% of penile squamous cell carcinomas. The RaSH approach identified differential expression of Annexin A1 (ANXA1), p16, RPL6, PBEF1 and KIAA1033 in high-risk HPV positive penile carcinoma; ANXA1 and p16 were overexpressed in penile squamous cells positive for high-risk HPVs compared to normal penile samples by qPCR. ANXA1 and p16 proteins were significantly more expressed in the cells from high-risk HPV-positive penile carcinoma as compared to HPV-negative tumors (p<0.0001) independently of the subtype of the carcinoma. Overexpression of ANXA1 might be mediated by HPV E6 in penile squamous cell carcinoma of patients with high-risk HPVs, suggesting that this gene plays an important role in penile cancer. © 2013 Calmon et al.

Epigenetic mechanisms in penile carcinoma

Penile carcinoma (PeCa) represents an important public health problem in poor and developing countries. Despite its unpredictable behavior and aggressive treatment, there have only been a few reports regarding its molecular data, especially epigenetic mechanisms. The functional diversity in different cell types is acquired by chromatin modifications, which are established by epigenetic regulatory mechanisms involving DNA methylation, histone acetylation, and miRNAs. Recent evidence indicates that the dysregulation in these processes can result in the development of several diseases, including cancer. Epigenetic alterations, such as the methylation of CpGs islands, may reveal candidates for the development of specific markers for cancer detection, diagnosis and prognosis. There are a few reports on the epigenetic alterations in PeCa, and most of these studies have only focused on alterations in specific genes in a limited number of cases. This review aims to provide an overview of the current knowledge of the epigenetic alterations in PeCa and the promising results in this field. The identification of epigenetically altered genes in PeCa is an important step in understanding the mechanisms involved in this unexplored disease. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Prevalência e fatores associados á verrugas anogenitais em homens portadores de HIV/AIDS atendidos em serviço especializado

Pós-graduação em Doenças Tropicais - FMB

A Nonsense Mutation in the IKBKG Gene in Mares with Incontinentia Pigmenti.

Ectodermal dysplasias (EDs) are a large and heterogeneous group of hereditary disorders characterized by abnormalities in structures of ectodermal origin. Incontinentia pigmenti (IP) is an ED characterized by skin lesions evolving over time, as well as dental, nail, and ocular abnormalities. Due to X-linked dominant inheritance IP symptoms can only be seen in female individuals while affected males die during development in utero. We observed a family of horses, in which several mares developed signs of a skin disorder reminiscent of human IP. Cutaneous manifestations in affected horses included the development of pruritic, exudative lesions soon after birth. These developed into wart-like lesions and areas of alopecia with occasional wooly hair re-growth. Affected horses also had streaks of darker and lighter coat coloration from birth. The observation that only females were affected together with a high number of spontaneous abortions suggested an X-linked dominant mechanism of transmission. Using next generation sequencing we sequenced the whole genome of one affected mare. We analyzed the sequence data for non-synonymous variants in candidate genes and found a heterozygous nonsense variant in the X-chromosomal IKBKG gene (c.184C>T; p.Arg62*). Mutations in IKBKG were previously reported to cause IP in humans and the homologous p.Arg62* variant has already been observed in a human IP patient. The comparative data thus strongly suggest that this is also the causative variant for the observed IP in horses. To our knowledge this is the first large animal model for IP.

Anal warts and their predictors among HIV-infected women

Human papillomavirus (HPV) is a necessary cause of cervical cancer and is also strongly associated with anal cancer. While different factors such as CD4+ cell count, HIV RNA viral load, smoking status, and cytological screening results have been identified as risk factors for the infection of HPV high-risk types and associated cancers, much less is known about the association between those risk factors and the infection of HPV low-risk types and anogential warts. In this dissertation, a public dataset (release P09) obtained from the Women's Interagency HIV Study (WIHS) was used to examine the effects of those risk factors on the size of the largest anal warts in HIV-infected women in the United States. Linear mixed modeling was used to address this research question. ^ The prevalence of anal warts at baseline for WIHS participants was higher than other populations. Incidence of anal warts in HIV-infected women was significantly higher than that of HIV-uninfected women [4.15 cases per 100 person-years (95% CI: 3.83–4.77) vs. 1.30 cases per 100 person-years (95% CI: 1.00–1.58), respectively]. There appeared to be an inverse association between the size of the largest anal wart and CD4+ cell count at baseline visit, however it was not statistically significant. There was no association between size of the largest anal wart and CD4+ cell count or HIV RNA viral load over time among HIV-infected women. There was also no association between the size of the largest anal wart and current smoking over time in HIV-infected women, even though smokers had larger warts at baseline than non-smokers. Finally, even though a woman with Pap smear results of ASCUS/LGSIL was found to have an anal wart larger than a woman with normal cervical Pap smear results the relationship between the size of the largest anal wart with cervical Pap smear results over time remains unclear. ^ Although the associations between these risk factors and the size of the largest anal wart over time in HIV-infected women could not be firmly established, this dissertation poses several questions concerning anal wart development for further exploration: (1) the role of immune function (i.e., CD4+ cell count), (2) the role of smoking status and the interaction between smoking status with other risk factors (e.g., CD4+ cell count or HIV RNA viral load), (3) the molecular mechanism of smoking on anal warts over time, (4) the potential for development of a screening program using anal Pap smear in HIV-infected women, and (5) how cost-effective and efficacious would an anal Pap smear screening program be in this high-risk population. ^

Lesiones estomatológicas del VPH genotipo 16 en la pre-adolescencia

El virus del Papiloma Humano infecta de manera selectiva al epitelio de la piel y las mucosas. Cuando se producen las infecciones, éstas pueden ser asintomáticas, provocando lesiones de tipos verrugosos o asociados a diversas neoplasias, benignos o malignos del tracto respiratorio superior y la cavidad bucal principalmente. Se presenta el caso de una niña con lesiones orales producidas por el VPH. Las lesiones se manifiestan clínicamente: elevadas, pediculadas y de superficie papilar; otras son planas y difusas sobre una base sésil.

Production of infectious bovine papillomavirus from cloned viral DNA by using an organotypic raft/xenograft technique

Bovine papillomavirus type 1 (BPV-1) induces fibropapillomas in its natural host and can transform fibroblasts in culture. The viral genome is maintained as an episome within fibroblasts, which has allowed extensive genetic analyses of the viral functions required for DNA replication, gene expression, and transformation. Much less is known about BPV-1 gene expression and replication in bovine epithelial cells because the study of the complete viral life cycle requires an experimental system capable of generating a fully differentiated stratified bovine epithelium. Using a combination of organotypic raft cultures and xenografts on nude mice, we have developed a system in which BPV-1 can replicate and produce infectious viral particles. Organotypic cultures were established with bovine keratinocytes plated on a collagen raft containing BPV-1-transformed fibroblasts. These keratinocytes were infected with virus particles isolated from a bovine wart or were transfected with cloned BPV-1 DNA. Several days after the rafts were lifted to the air interface, they were grafted on nude mice. After 6–8 weeks, large xenografts were produced that exhibited a hyperplastic and hyperkeratotic epithelium overlying a large dermal fibroma. These lesions were strikingly similar to a fibropapilloma caused by BPV-1 in the natural host. Amplified viral DNA and capsid antigens were detected in the suprabasal cells of the epithelium. Moreover, infectious virus particles could be isolated from these lesions and quantitated by a focus formation assay on mouse cells in culture. Interestingly, analysis of grafts produced with infected and uninfected fibroblasts indicated that the fibroma component was not required for productive infection or morphological changes characteristic of papillomavirus-infected epithelium. This system will be a powerful tool for the genetic analysis of the roles of the viral gene products in the complete viral life cycle.

Position measurements at five permanent GPS stations in the Bavarian Alps as part of the Geodetic Alpine Integrated Network (GAIN) of the ALPS-GPSQUAKENET project

In the frame of the transnational ALPS-GPSQUAKENET project, a component of the Alpine Space Programme of the European Community Initiative Programme (CIP) INTERREG III B, the Deutsches Geodätisches Forschungsinstitut (DGFI) in Munich, Germany, installed in 2005 five continuously operating permanent GPS stations located along the northern Alps boundary in Bavaria. The main objective of the ALPS-GPSQUAKENET project was to build-up a high-performance transnational space geodetic network of Global Positioning System (GPS) receivers in the Alpine region (the so-called Geodetic Alpine Integrated Network, GAIN). Data from this network allows for studying crustal deformations in near real-time to monitor Earthquake hazard and improve natural disaster prevention. The five GPS stations operatied by DGFI are mounted on concrete pillars attached to solid rock. The names of the stations are (from west to east) Hochgrat (HGRA), Breitenberg (BREI), Fahrenberg (FAHR), Hochries (HRIE) and Wartsteinkopf (WART). The provided data series start from October 7, 2005. Data are stored with a temporal spacing of 15 seconds in daily RINEX files.

Kryzys demokracji liberalnej - wybrane problemy rządzenia, legitymizacji i reprezentacji

Główna problematyka zawarta w tekście dotyczy: (1) znaczenia i zakresu kryzysu w gospodarce i polityce, (2) przyjęcia przez państwo i społeczeństwo logiki racjonalności ekonomicznej jako paradygmatu postępowania, (3) przewartościowania pojęcia polityki, co wiąże się m.in. z przyjęciem przez rządzących roli zarządców wybranych sfer państwa oraz z posługiwaniem się przez nich logiką „mieszanej racjonalności” („logiką władzy” i „logiką racjonalności ekonomicznej”), (4) wyzwań związanych z dystrybucją dóbr, (5) reprezentacji i legitymizacji w demokracji liberalnej. Gospodarka kapitalistyczna wpływa na wszystkie sfery życia społecznego, co zmusza do przedstawienia jej „modus operandi”. Charakterystyczne cechy oddziaływania to: (1) racjonalność formalna, (2) dogmat efektywności i ilościowej mierzalności, (3) reprodukcja ideologii mówiącej o wolnej woli jednostki, niezależnie od kontekstu społecznego, (4) wymuszanie odpowiedniej dla siebie reprodukcji siły roboczej, (5) kolonizacja kolejnych sfer aktywności społecznej (np. edukacji i szkolnictwa wyższego), (6) wpływ na wykluczenie grup społecznych ze względu na poziom zabezpieczenia materialnego. Wszystko to sprowadzić można do pojęcia logiki racjonalności ekonomicznej. Rządzący posługują się „mieszaną strategią”, która oparta jest na dwóch logikach postępowania – (1) logice władzy, (2) logice racjonalności ekonomicznej. Logika władzy to nic innego jak dążenie do zdobycia i utrzymania władzy, gdzie władza sama w sobie staje się celem, natomiast struktury państwa stanowią przestrzeń, którą należy przejąć lub opanować. Rządzący aby ukryć swoją bezideowość i konflikty w walce o przejęcie struktur państwa uprawiają politykę „na zewnątrz”, która przyjmuje formę „festiwalu” agonicznego dyskursu. Taka polityka możliwa jest dzięki rozdawnictwu podczas redystrybucji dóbr (niezgodnie z racjonalnością ekonomiczną) lub/i dzięki instrumentalnemu traktowaniu dystrybucji uznania. W związku z niemożnością utrzymania wysokiego poziomu rozdawnictwa, szczególnie w sytuacji kryzysu gospodarczego, rządzący chętnie posługują się logiką racjonalności ekonomicznej. Rozwiązania oparte na racjonalności ekonomicznej, mimo ich negatywnego odbioru przez społeczeństwo, wprowadzane są przy zastosowaniu argumentacji zagrożenia bezpieczeństwa (gospodarczego, socjalnego, narodowego itd.). Tym samym państwo wycofuje się z rządzenia na rzecz zarządzania niektórymi sferami państwa. Nie można tego nazwać inaczej jak „ucieczką” od odpowiedzialności, co jest szczególnie zauważalne w sytuacjach destabilizacji gospodarczej. W takich sytuacjach mamy do czynienia z „outsourcingiem zadań” państwa, co przyjmować może różne formy – (1) przenoszenie funkcji na inne instytucje przy zachowaniu kompetencji kontrolnych lub (2) przenoszenie obowiązków na inne własne instytucje, które wcześniej pełniły inną rolę. Wszystko to można nazwać rekonfiguracją funkcji państwa w związku z dominacją gospodarki kapitalistycznej i oddziaływaniem logiki racjonalności ekonomicznej. W tekście podjęto również problem dystrybucji dóbr i uznania, jednakże jedynie w aspekcie jej instrumentalizacji przez rządzących. Można wysunąć tezę, że liberalne koncepcje wolności jednostki oraz priorytet dla własności prowadzą do łatwiejszego ideologicznego uzasadnienia stosowania mieszanych strategii i racjonalności. W tekście przedstawiono też tezę o instrumentalizacji dystrybucji dóbr, tzn. instrumentalnego wykorzystywania dowartościowania różnych mniejszości w ramach systemu politycznego. Należy też stwierdzić, że dominacja logiki wolnego rynku prowadzi do deprecjacji redystrybucji dóbr w stosunku do gloryfikacji problematyki uznania. Tekst jest jedynie zarysowaniem problematyki wyczerpywania się formuły demokracji liberalnej, co przedstawiono na wybranych zagadnieniach. Podjęty problem demokracji liberalnej nie skupia się na próbie odtworzenia modelu tego rodzaju demokracji, raczej ważniejsze było stwierdzenie przejmowania w działaniu czegoś, co można określić mianem logiki racjonalności ekonomicznej. Wartą dalszego analizowania jest sama logika „mieszanej racjonalności”, którą sprowadzono do przenikania się „logiki władzy” i „logiki racjonalności ekonomicznej”.