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While the incidence of infections with the human immunodeficiency virus largely remained unchanged in Germany, an increase of other sexually transmitted infections (STIs) was observed. The aim was to analyse the effectiveness of our sexual education lecture for students in improving the awareness, knowledge and prevention of STIs. We conducted a cross-sectional survey after students had attended our extra-curricular lecture at the Department of Dermatology of the Ludwig-Maximilians-University of Munich, Germany (LMU). We compared the data with a previously performed study in which the same survey was carried out before the lecture had started. A total of 5866 questionnaires were included in the analysis. After attending the lecture significantly more students were aware of STIs (syphilis: 36.8% (before) vs. 63.5% (after); chlamydia: 30.5% vs. 49.3%; gonorrhoea: 22.4% vs. 38.2%; human papillomaviruses (HPV): 17.7% vs. 30.2%), the transmission pathways of STIs (oral: 36.6% vs. 82.6%; vaginal: 81.8% vs. 97.3%; anal: 42.8% vs. 94.0%; penile: 68.7% vs. 92.1%), knew that the HPV vaccination is directed against a virus (36.8% vs. 56.9%) and were interested in receiving a vaccination (57.7% vs. 78.8%). This study demonstrates the positive educative effects of our lecture for awareness and improved knowledge of STIs. To satisfy the need for a comprehensive sexual education, a combination of school and health facility-based programmes should be implemented as one single lecture cannot convey the entire information about STIs.

Although identified as an emerging scientific paradigm, social network research has yet to be developed fully in tourism studies. Social network theory focuses on the ties between actors within a particular network. An individual can influence his or her success through the structure, extent and diversity of their network. Within the tourism industry, the study of social networks can be used to enhance understanding of the interactions that take place within, or among businesses, by examining the formal and informal connections linking them together. This study examined involvement or membership in associations (networks) of five key tourism industry segments in a thriving tourism region along participation and coverage dimensions. The results showed that tourism sectors participate differently in social networks. Specifically, the hotel and lodging sector participates in a greater number and covers more types of networks than the retail/shopping sector.

Purpose: Epileptic seizures are associated with a dysregulation of electrical brain activity on many different spatial scales. To better understand the dynamics of epileptic seizures that is how the seizures initiate propagate and terminate it is important to consider changes of electrical brain activity on different spatial scales. Herein we set out to analyze periictal electrical brain activity on comparatively small and large spatial scales by assessing changes in single intracranial electroencephalography (EEG) signals and of averaged interdependences of pairs of EEG signals. Methods: Single and multiple EEG signals are analyzed by combining methods from symbolic dynamics and information theory. This computationally efficient approach is chosen because at its core it consists of analyzing the occurrence of patterns and bears analogy to classical visual EEG reading. Symbolization is achieved by first mapping the EEG signals into bit strings that is long sequences of zeros and ones depending solely on whether their amplitudes increase or decrease. Bit strings reflect relational aspects between consecutive values of the original EEG signals but not the values themselves. For each bit string the relative frequencies of the different constituent short bit patterns are then determined and used to compute two information theoretical measures: (1) redundancy (R) of single bit strings characterizes electrical brain activity on a comparatively small spatial scale represented by a single EEG signal and (2) averaged pair wise mutual information with all other bit strings (M) which allows tracking of larger scale EEG dynamics. Key Findings: We analyzed 20 periictal intracranial EEG recordings from five patients with pharmacoresistant temporal lobe epilepsy. At seizure onset R first strongly increased and then decreased toward seizure termination whereas M gradually increased throughout the seizure. Bit strings with maximal R were always derived from EEG signals recorded from the visually identified seizure onset zone. When compared to the bit strings derived from other EEG signals their M was relatively smaller. These findings are consistent with a strong but transient occurrence of information poor that is redundant electrical brain activity on a smaller spatial scale which is particularly pronounced in the seizure onset zone. On a larger spatial scale a progressively more collective state emerges as revealed by increasing amounts of mutual information. Significance: Information theoretical analysis of bit patterns derived from EEG signals helps to characterize periictal brain activity on different spatial scales in a quantitative and efficient way and may provide clinically relevant results.

We studied the effects of liming on soils and forest songbirds as well as vegetation and calcium-rich invertebrate prey variables that were predicted to link birds to changes in soil conditions. We observed increases in soil pH, calcium, and magnesium, as well as in songbird abundances in response to lime application, with continuing increases through five years after liming. We observed an overall increase in snail abundance on limed sites, but an initial peak of a 23 fold increase three years after liming was reduced to an 11 fold increase five years after liming. We observed an increase in forb ground cover on limed sites, but liming had no effect on millipede abundance or other vegetation measures. Of the variables we measured, snail abundance was the most likely mechanism for the response in bird abundances. Because we observed continued benefits of liming up to five years post treatment, we concluded that liming is a very promising technique for restoring forest ecosystems impacted by acidic deposition.

Objective: To determine the ability to produce comparable superimpositions using hand tracing and digital methods (Dolphin v10). In addition, if the two methods were comparable, we wanted to determine if a difference existed between the best-fit cranial base superimposition and S-N superimpositions using the digital method. Methods and Materials: Sixty-four initial (T1) and final (T2) cephalometric film radiographs were obtained. Cranial base and regional superimpositions were completed independently for each pair of radiographs by either hand tracing and digital methods. To quantitatively evaluate the differences between the two methods, the hand and digital superimpositions were digitized to obtain x-y coordinates of routine cephalometric landmarks at T2. Linear distance between multiple corresponding (hand and digital) T2 cephalometric landmark locations (e.g., A point) were measured and defined as the T2 landmark distance (T2 LD). Additionally, 61 patient records were used to compare the digital method for best-fit cranial base superimpositions versus S-N superimpositions. A Friedman test was applied to examine for differences. Results: The upper 95% confidence limit for the mean of the T2 LD for hand and digital superimposition methods was 1 mm for most landmarks. Conclusion: This study validates the use of superimpositions produced by Dolphin Imaging version 10 and is a necessary step forward toward widespread acceptance of digital superimpositions.

Inhibition of gap junctional intercellular communication (GJIC) and the activation of intracellular mitogenic pathways are common hallmarks of epithelial derived cancer cells. We previously determined that the 1-methyl and not the 2-methyl isomer of anthracene, which are prominent cigarette smoke components, activated extracellular receptor kinase, and inhibited GJIC in WB-F344 rat liver epithelial cells. Using these same cells, we show that an immediate upstream response to 1-methylanthracene was a rapid ( LT 1 min) release of arachidonic acid. Inhibition of phosphatidylcholine-specific phospholipase C prevented the inhibition of GJIC by 1-methylanthracene. In contrast, inhibition of phosphatidylinositol specific phospholipase C, phospholipase A(2), diacylglycerol lipase, phospholipase D, protein kinase C, and tyrosine protein kinases had no effect on 1-methylanthracene-induced inhibition of GJIC. Inhibition of protein kinase A also prevented inhibition of GJIC by 1-methylanthracene. Direct measurement of phosphatidylcholine-specific phospholipase C and sphingomyelinase indicated that only phosphatidylcholine-specific phospholipase C was activated in response to 1-methylanthracene, while 2-methylanthracene had no effect. 1-methylanthracene also activated p38-mitogen activated protein kinase; however, like extracellular kinase, its activation was not involved in 1-methylanthracene-induced regulation of GJIC, and this activation was independent of phosphatidylcholine-specific phospholipase C. Although mitogen activated protein kinases were activated, Western blot analyzes indicated no change in connexin43 phosphorylation status. Our results indicate that phosphatidylcholine-specific phospholipase C is an important enzyme in the induction of a tumorigenic phenotype, namely the inhibition of GJIC; whereas mitogen activated protein kinases triggered in response to 1-methylanthracene, were not involved in the deregulation of GJIC.

Kutane Lymphome sind extranodale Non-Hodgkin-Lymphome reifer T-oder B-Lymphozyten, welche die Haut als Zielorgan haben und dort persistieren. Sie zeigen eine grose Bandbreite klinischer und histologischer Erscheinungsformen. Aktuelle Daten aus der Grundlagenforschung zur Tumorbiologie von Malignomen ermoglichten die Entwicklung neuer Ansatze fur eine zielgerichtete Therapie. Zahlreiche Studienergebnisse zeigen vielversprechende Daten. Diese Arbeit gibt einen Uberblick uber den aktuellen Stand zielgerichteter Therapien bei Patienten mit kutanen T- und B-Zell-Lymphomen – auf der Basis von Fusionsproteinen, monoklonalen Antikorpern sowie der neuen Gruppe der Histon-Deacetylase-Inhibitoren.

Dicumyl peroxide (di-CuOOH) and benzoyl peroxide (BzOOH) act as tumor promoters in SENCAR mice, whereas di-tert-butylhydroperoxide does not. Tumor promotion requires the removal of growth suppression by inhibition of gap junctional intercellular communication (GJIC) and the induction of mitogenic intracellular pathways. We showed that di-CuOOH and BzOOH both reversibly inhibited GJIC and transiently activated mitogen-activated protein kinase, specifically, the extracellular receptor kinase at noncytotoxic conditions in WB-F344 rat liver epithelial cells, whereas the non-tumor-promoting di-tert-butylhydroperoxide did not inhibit GJIC or activate extracellular receptor kinase. di-CuOOH but not BzOOH inhibited GJIC through a phosphatidylcholine-specific phospholipase C-dependent mechanism. N-acetylcysteine (NAC) was needed to prevent a cytotoxic, glutathione-depleting effect of BzOOH, whereas di-CuOOH was noncytotoxic and did not alter glutathione levels at all doses and times tested. Pretreatment of WB-F344 cells with resveratrol, a polyphenolic antioxidant present in red wine, prevented at physiological doses the inhibition of GJIC by di-CuOOH but not from BzOOH and was effective in significantly preventing extracellular receptor kinase activation by both peroxides. NAC did not prevent any of the peroxide effects on either GJIC or extracellular receptor kinase, suggesting a specific antioxidant effect of resveratrol.

The inhibition of apoptosis and gap junctional intercellular communication (GJIC) has been implicated in tumor promotion. Ionizing radiation and oxidative toxicants activate sphingomyelinases resulting in the release of ceramides that control cell proliferation and apoptosis. A rat liver epithelial cell line treated with ceramides containing a 6 (C6) or 8 (C8) carbon acyl-group were potent inhibitors of GJIC and apoptosis, whereas a C2-ceramide was only a weak inhibitor of GJIC and strong inducer of apoptosis. Apoptosis induced by either serum deprivation or C2-ceramide was inhibited by the GJIC inhibitory C8-ceramide. In conclusion, these results suggest that a chronic release of ceramides with acyl groups larger than C6 might act as tumor promoters.

Many tumor promoters suppress the immune system; however, the direct effect of immunosuppressants on the tumorigenic pathways of nonimmune cells in solid tissue has not been well documented. Cannabinoids were chosen to explore this question further. Cannabinoids are immune modulators that affect specific intracellular signaling pathways in leukocytes. Since these compounds are nongenotoxic, any tumorigenic effect that might be associated with these compounds would need to occur through an epigenetic mechanism. Therefore, we determined the effect of Δ9-THC and CBN, 2 plant-derived cannabinoids, on 2 key epigenetic markers of tumor promotion: inhibition of GJIC, which is essential in removing a cell from growth suppression, and activation of the ERK–MAPK pathway, which is crucial in activating the appropriate genes for mitogenesis. Both Δ9-THC and CBN reversibly inhibited GJIC at noncytotoxic doses (15 μM) in a normal diploid WB rat liver epithelial oval cell line within 20 min and activated ERK1 and ERK2 within 5 min. Inhibition of MEK with PD98059 prevented the inhibition of GJIC by either cannabinoid, suggesting that inhibition of GJIC was MEK-dependent. Based on RT-PCR analysis and employment of an antagonist of CB1 and CB2, the effects on GJIC and MAPK were independent of both cannabinoid receptors. Cannabinoids affected crucial epigenetic pathways associated with cell proliferation in a rodent liver epithelial cell model system. © 2002 Wiley-Liss, Inc.

Many polycyclic aromatic hydrocarbons (PAHs) are known carcinogens. A considerable amount of research has been devoted to predicting the genotoxic, tumor-initiating potential of PAHs based on chemical structure. However, information on the correlation of structure with the non-genetoxic, epigenetic events of tumor promotion is sparse. PAHs containing a bay or bay-like region were shown to be potent inhibitors of gap-junctional intercellular communication (GJIC), an epigenetic event involved in the removal of an initiated cell from growth suppression. We tested the epigenetic toxicity of PAHs containing bay-like regions by comparing the effects of methylated vs. chlorinated isomers of anthracene on the temporal activation of mitogen-activated protein kinase (MAPK) and the regulation of GJIC. Specifically, we used anthracene, 1-methylanthracene, 2-methylanthracene, 9-methylanthracene, 9,10-dimethylanthracene, 1-chloroanthracene, 2-chloroanthracene, and 9-chloroanthracene. We determined the effect of these compounds on GJIC and on the activation of extracellular receptor kinase (ERK 1 and 2), a MAPK, in F344 rat liver epithelial cells. Results showed that bay or bay-like regions, formed by either chlorine or a methyl group, reversibly inhibited GJIC at the same doses, time, and time of recovery, whereas the linear-planar isomers had no effect on GJIC. Similarly, the GJIC-inhibitory isomers also induced the phosphorylation of ERK 1 and ERK 2, while the non-inhibitory isomers had no effect on the activation of these MAPKs. MAPK activation occurred 10-20 min after the inhibition of GJIC, which indicates that MAPK is not involved in the initial regulation of GJIC; instead altered GJIC may be affecting MAPK activation. The present study revealed that there are structural determinants of PAHs, which clearly affect epigenetic events known to be involved in the non-genetoxic steps of tumor promotion. These events are the release of a cell from growth suppression involving the reduction of GJIC, followed by the activation of intracellular mitogenic events.

Polycyclic aromatic hydrocarbons (PAHs) are known carcinogens, but most research on their toxicity in the development of human-risk assessment models has focused on genotoxicity. Many nongenotoxic PAHs, however, have been shown to be epigenetically toxic by disrupting gap junctional intercellular communication (GJIC), an effect which has been affiliated with tumor promotion. We therefore used GJIC as an epigenetic biomarker to assess the toxic effect of a nonaqueous phase liquid (NAPL) mixture of PAHs commonly found in coal tar and creosote products. The NAPL mixture consisted of toluene, naphthalene, 1-methylnaphthalene, 2-ethylnaphthalene, acenaphthene, fluorene, phenanthrene, fluoranthene, and pyrene. This mixture reversibly inhibited GJIC at a maximal and noncytotoxic dose of 60 μM. Inhibition occurred within 5 min, indicating a post-translational modification of gap junction proteins. Biodegradation of globules of this mixture suspended in mineral media by a microorganism isolated from creosote-conta...

The purpose of the study was to compare Quasi-Static (QS) and harmonic (CSM) methods of indentation testing. Bone sections were obtained from mid-femoral diaphyses of dogs which received a pair of calcein labels. Labeled (n = 35) and unlabeled (n = 112) osteons were identified. Indentation modulus (IM) and hardness (H) for the CSM method were collected during the entire loading cycle to peak depth, while IM and H for QS method were calculated at a peak depth of 500 nm. Results: The mean (SD) of the IM and H for labeled osteons were as follows: QS IM = 15.3 GPa (3.85) versus CSM IM = 14.7 GPa (3.58); P = .52 and QS H = .39 GPa (.171) versus CSM H = .42 GPa (.146); P = .32. The mean (SD) of the IM and H for unlabeled osteons were as follows: QS IM = 21.5 GPa (2.80) versus CSM IM = 20.6 GPa (2.53); P = .054 and QS H = .64 GPa (.117) versus CSM H = .70 GPa (.120); P = .017. There was no difference in IM and H for the two methods, except for H of the unlabeled osteons. In addition, for the CSM method, IM at 100 nm, 200 nm, 300 nm, 400 nm and 500 nm were not statistically significant different (P = .06). Bone is viscoelastic at an organ level. However, this component of its behavior was not detected at the length scale examined.

The purpose of the study was to compare indentation modulus (IM) and hardness of condylar bone in young and adult dogs. In addition we desired to examine histologic sections for bone formation activity in the two groups. Mandibular condyles were obtained from adult (1- to 2-year-old) and young (approximately 5-m old) dogs. Two sections/condyle were obtained and one was processed for histomorphometry and the other for mechanical analyses. Indents were made on moist condylar trabecular bone to a depth of 500 nm at a loading rate of 10 nm/s using a custom-made hydration system to obtain IM and hardness. Histomorphometric analyses measured the bone volume/total volume (BV/TV%) and ratio of labeled to unlabeled bone within the condyle. Data were analyzed using a repeated-measures factorial analysis of variance and Tukey-Kramer method. Overall, the IM of the adult condyles (10.0+/-3.4 GPa, Mean+/-SD) were significantly (P

The development of metastatic capacity in a tumor is a multistep process characterized both by the loss of normal behavior and by the acquisition of new properties (Fidler and Hart 1982; Hart and Saini 1992). The identification of molecules which are newly expressed, altered or lost during this process can lead to an understanding of the molecular basis of tumor progression and metastasis formation and can also lead to the development of diagnostic and therapeutic tools. We have used monoclonal antibodies to define, in human melanoma, molecules that change their expression patterns in concert with the appearance of parameters known to be predictive for the occurrence of metastatic disease (Clark et al. 1984; Herlyn et al. 1987; Johnson 1995). Using this approach the 113kDa cell surface glycoprotein MUC18 was identified as a human melanoma associated antigen that increases in expression as tumors increase in vertical thickness and begin to acquire metastatic potential (Lehmann et al. 1987).

The metabolism of the o-quinone derivative of estrone, 3,4-estrone quinone (3,4-EQ), has been investigated in human breast cancer cells. Unlike the p-quinone, diethylstilbestrol 4',4"-quinone, 3,4-EQ was not a substrate for the two-electron reduction catalyzed by the putative detoxifying enzyme, NAD(P)H:quinone reductase (DT diaphorase; DT D). Accordingly, the DNA damage induced by 3,4-EQ in human MCF-7 cells was not affected by an inhibitor of DT D. Although 3,4-EQ was not an apparent substrate for the two-electron reduction catalyzed by DT D, this o-quinone was a substrate for the one-electron reduction catalyzed by cytochrome P450 reductase. The one-electron reduction of 3,4-EQ catalyzed by cytochrome P450 reductase occurred in the face of a significant and potentially physiologically relevant spontaneous reduction of 3,4-EQ by NADPH. The impact of purified superoxide dismutase (SOD) upon the production of hydrogen peroxide produced as a consequence of 3,4-EQ metabolism was evaluated; surprisingly, SOD inhibited the hydrogen peroxide produced by this o-quinone. Possible reasons for the SOD-mediated inhibition of redox cycling of 3,4-EQ are discussed. In summary, important differences in the metabolism of 3,4-EQ vis-a-vis o- and p- quinones have been observed, and the implications of these differences are discussed.

Nach Zugabe von aromatischen o-Diaminen und o-Aminothiophenol zu Pilzkulturen von Cordyceps militaris und Saccharomyces cerevisiae erfolgte eine Acetylierung am Aminostickstoff durch Acetyl-Coenzym A unter gleichzeitiger Cyclisierung zu 2-Methylbenzimidazolen bzw. 2-Methylbenzthiazol. Es konnte gezeigt werden, das die Acetylierung durch Arylaminacetylase katalysiert wird, wahrend die Cyclisierung infolge der energiereichen Form der Essigsaure spontan erfolgt.

Die Erfolge der operativen Therapie organischer Gefasleiden wahrend der letzten Jahre sind nicht zuletzt auch darauf zuruckzufuhren, das wir heute in der Lage sind, fur derartige - in der Regel langdauernde und schwere — Eingriffe schonende Anaesthesien durchzufuhren.

Many polycyclic aromatic hydrocarbons (PAHs) are known carcinogens, and a considerable amount of research has been devoted to predicting the tumor-initiating potential of PAHs based on chemical structure. However, there has been little research into the effects of PAHs on the epigenetic events of tumor promotion and no structural correlation has been made thereof. Gap junctional intercellular communication (GJIC) activity was used in this study as an epigenetic biomarker to determine the structure-activity relationships of twelve different PAHs. The PAHs used were naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, anthracene, 1-methylanthracene, 2-methylanthracene, 9-methylanthracene, 9, 10-dimethylanthracene, phenanthrene, fluorene, 1-methylfluorene, and fluoranthene. Results showed that PAHs containing bay or baylike regions inhibited GJIC more than did the linear PAHs. The nonnaphthalene PAHs were not cytotoxic as determined by a vital dye uptake assay, but the naphthalene compounds were cytotoxic at the higher doses, indicating that the down regulation of GJIC by these naphthalenes could be a consequence of general membrane damage. Inhibition of GJIC by all the inhibitory PAHs was reversed when the cells were refreshed with PAH-free growth medium. Inhibition of GJIC occurred within 0.5-5 min and correlated with the aqueous solubility of the PAHs. The present study revealed that there are structural determinants of epigenetic toxicity as determined by GJIC activity. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10

alpha-Functionalized terthiophenes containing disulfide (-S-T-3-H)(2) and alkanethiol (HS-(CH2)(11)-T-3-H) anchoring groups have been synthesized for direct immobilization onto gold. Monolayer stru ...