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Little is known about the etiological factors involved in cutaneous malignant melanomas. Environmental, hormonal and genetic factors have been implicated in its pathogenesis, these include lower skin phototypes, with fair or red hair and blue eyes, the amount of sun exposure and previous sunburns, a familiar predisposition and increased number of dysplastic nevi. The role of human papillomavirus HPV ; in many neoplastic diseases, including cervical cancer and non-melanoma skin tumours, has been widely studied. Moreover, HPV has been detected in some biopsy specimens from malignant melanomas, suggesting that HPV can be correlated with a more rapid melanoma progression and a poorer clinical outcome. In this study, to further investigate the presence of HPV DNA, we performed two different PCR-ELISA methods on 54 malignant melanomas, 33 dysplastic nevomelanocytic nevi Clark's nevi ; and 15 healthy skins. We utilized two different consensus primer sets to optimize the detection of HPV DNA and, in particular, the consensus primer pair MY09 MY11 to amplify a 450 bp segment of the L1 gene of 30 HPV genotypes and the consensus primer pair GP5 GP6 to amplify a 150 bp segment of the L1 gene of 24 HPV genotypes. In both PCR-ELISA assays, amplified products were separately hybridized with 8 type-specific probes for high-risk HPV genotypes HPV 16, 18, 31, and 52 ; . HPV DNA was detected in 9 17% ; melanomas and 5 15% ; dysplastic nevi with MY PCR-ELISA, while with GP PCR-ELISA, HPV was identified in 13 24% ; melanomas and 8 24% ; dysplastic nevi. All HPV positive samples in MY PCR were positive also in GP PCR. The presence of HPV in malignant melanomas was not correlated to Breslow thickness microstage or other severity parameters. In conclusion the presence of high-risk human papillomaviruses in a relevant number of malignant melanomas and of dysplastic nevi should stimulate future studies to investigate if HPVs play an etiological role in the molecular mechanism of melanoma development.
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Thomson Healthcare Inc., Physicians' Desk Reference, 60th ed. Montvale, New Jersey: Thomson PDR, 2006 ; , pp. 3, 169-3, 172. U.S. Drug Enforcement Administration and U.S. Department of Justice, Drugs of Abuse Washington, D.C., 2005 ; , p. 7, available in pdf format at : usdoj.gov dea pubs abuse doa-p . Last visited August 2, 2006. ; U.S. National Library of Medicine and the National Institutes of Health, "Narcotic Analgesics For Pain Relief, " : nlm. nih.gov medlineplus druginfo uspdi 202390. html. Last visited August 8, 2006. ; WebMD, "Scabies, " : webmd hw skin and beauty hw171813 . Last visited August 24, 2006. ; U.S. National Library of Medicine and the National Institutes of Health, "Phenobarbital, " : nlm.nih.gov medlineplus druginfo medmaster a682007. html. Last visited August 28, 2006. ; U.S. Drug Enforcement Administration and U.S. Department of Justice, Drugs of Abuse, p .4. U.S. National Library of Medicine and the National Institutes of Health, "Phenobarbital, for example, rxlist.
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The slice and was slowly washed out see Discussion ; . The effect of Tam on amplitude was almost completely reversible after 24 min washing Fig. 2C ; . In the same way, the increase in frequency was already detectable during Tam application compare the control trace and the trace recorded at 1214 min after addition of Tam in Fig. 2A ; but developed further during the initial washing period. In this motoneuron, the effect on frequency was particularly slow and strong increase by a factor of 3.4 1214 min after Tam addition, maximum increase by a factor of 14.6 ; and was only partly reversed after 24 26 min washing Fig. 2D ; . At Tam induced a reliable increase in miniature amplitude in five of six experiments performed in the presence of cadmium, and the mean percentage increase of miniature amplitude was 79 35% 5 ; . Interestingly, in the cell that did not respond to Tam by an increase in mean miniature amplitude, the mean control value was particularly high 125 pA ; . At Tam also induced a reliable frequency increase in five of six experiments performed in the presence of cadmium. In the remaining cell, the control frequency was very high and too variable between 3.6 and 6.7 ; to allow detection of an effect of Tam. The maximum frequency increase was usually observed during Tam application, between 4 and 12 min after the beginning of perfusion with Tam. Figure 3 combines the results obtained with 2 m Tam in the absence or presence of cadmium in 3.4 mm ethanol ; . For each neuron, the mean miniature amplitude and the mean miniature frequency are reported in Fig. 3, A and B, respectively ; by plotting the maximum value with Tam as a function of the control value. The percentage increase of the mean miniature amplitude with Tam is given in Fig. 3C for each neuron. The increase factor of the mean miniature frequency by Tam is given in Fig. 3D for each neuron. Note that it could reach 15 at 2 Tam. Whatever the experimental conditions used, no effect of Tam 2 m ; was ever detected on the time course of decay of glycinergic miniature currents as already indicated by the normalized average traces of Fig. 1B; comparison performed for each neuron ; . The average sd ; of the mean T0.5 was 4.90 0.70 msec in the controls and 4.89 0.91 msec at the maximum Tam effect for the 10 experiments using 3.4 mm ethanol in which Tam increased the amplitude and or frequency of glycinergic miniatures. The average of the mean T0.5 was 4.96 0.74 msec in the controls and 4.76 0.91 msec at the maximum Tam effect for the five experiments using 17 mm ethanol in which Tam increased the amplitude of glycinergic miniatures. Another set of experiments was performed in the presence of 3.4 mm ethanol ; to test possible effects of a lower Tam concentration, 0.5 m. In these experiments, Tam was added for 1216 min. As illustrated in Fig. 3, even at 0.5 m, Tam could increase the mean amplitude and the mean frequency of glycinergic miniature currents. However, each of these effects was only observed with four of nine cells tested. The percentage increase of mean miniature amplitude induced by 0.5 m Tam was 47 14% 4 ; . In three of the cells that did not respond to Tam by an increase in mean miniature amplitude, the control value was particularly high 85 pA ; , as already noted above for experiments using 2 m Tam and 17 mm ethanol. Again, no effect of Tam was detected on the time course of decay of miniature currents. In conclusion, bath application of rather low concentrations of Tam 0.5 or 2 m ; can increase the mean amplitude and the mean frequency of glycinergic miniature currents, even in the.
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