The main etiological factor of precancerous lesion and invasive cervical cancer are oncogenic human papillomaviruses types (HPVs). The objective of this study was to establish the distribution of the most common HPVs in different cervical lesions and cancer prior to the implementation of organized population-based cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical specimens, collected through a 16-year period, were tested for the presence of HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11) and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58). Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV-prevalence was in the group 18–24 years, which decreased continuously with age (P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV types significantly increased (P<0.0001) with the severity of cervical lesions. HPV-16 was the most common type found with a prevalence (with or without another HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of undetermined significance, 14.4% in low-grade squamous intraepithelial lesions, 33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical cancer specimens (P<0.0001). This study provides comprehensive and extensive data on the distribution of the most common HPV types among Croatian women, which will enable to predict and to monitor the impact of HPV-vaccination and to design effective screening strategies in Croatia.
affecting the activities of relipidated or cell surface TF, exactly as observed. To test this hypothesis we have examined bovine PDI for traces of PL. The activation of prothrombin by factor Xa/Va is highly sensitive to the presence of PL. As noted with sTF, addition of bovine PDI, but not rhPDI, markedly increased prothrombin activation ( Figure 1B). Addition of annexin V, a phospholipid binding protein, completely attenuated the bovine PDI-mediated increase in sTF activity ( Figure 1C) and prothrombin activation (data not shown), further strengthening our hypothesis that the observed enhancing effects of bovine PDI stem from contamination of the reagent with PL. Consistent with this notion is our observation that pretreatment of bovine PDI with phospholipase C, which inhibits PL function by cleaving it at the phosphate group, abolished the enhancing effect of bovine PDI on sTF. Finally, in contrast to the data obtained with immunoprecipitation studies, 5 we found no evidence for the direct interaction of PDI with TF in Biacore binding studies ( Figure 1E). In summary, the enhancing effect of bovine PDI is not limited to its effects on sTF but also extends to activation of prothrombin by factors Xa/Va. Our present data suggest that the effect of bovine PDI on sTF (and prothrombin activation) is probably an artifact due to contamination of commercial bovine PDI with traces of PL. To the editor: Aberrant Ikaros, Aiolos, and Helios expression in Hodgkin and non-Hodgkin lymphomaIkaros transcription factors are regulators of lymphocyte development, and changes in their expression result in lymphoma development in mice. 1 Although expression of Ikaros family members has been studied in different leukemias, 2-4 it has not been previously reported in lymphoma. Thus, we tackle the question whether there is a quantitative difference in distribution of Ikaros, Aiolos, and Helios mRNA between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Formalin-fixed and paraffinembedded sections of lymph nodes from 41 patients were analyzed. 5 NHL is represented by the most frequent indolent follicular center cell lymphoma (FCC), the aggressive diffuse large B-cell lymphoma (DLBCL) and a less frequent anaplastic large cell lymphoma (ALCL; Figure 1). Subclassification of HL (mixed cellularity or nodular) did not reveal any difference in Ikaros family expression, so we rather present them as a single group. The experiments were approved by the Ethics Committee of the University of Zugreb Medical School. Informed consent was obtained in accordance with the Declaration of Helsinki. Figure 1 shows that the relative quantity of Ikaros and Helios mRNA is not statistically different among HL, DLBCL, FCC, ALCL, and normal controls tested (Ikaros: F (4,42) ϭ 0.612, P ϭ .656; Helios: F (4,42) ϭ 0.858, P ϭ .497; one-way ANOVA) On the other hand, analysis of the third Ikaros family member, Aiolos, showed a statistically significant difference among groups (F (4,42) ϭ 7.052, P Ͻ .01, one-way ANOVA) due to increase of its expression in FCC-NHL...
Primary mediastinal large B-cell lymphoma (PMLBCL) is a subset of LBCL with unique clinicopathologic features. Some studies have raised the question of differences in biological features and clinical course among patients from different parts of the world. We conducted a retrospective clinicopathologic analysis of 24 patients with PMLBCL from a single center in Croatia. We also conducted the first investigation of the frequency of lymphotropic viruses human herpesvirus 6 (HHV-6) and HHV-8 in lymphoid lesions of this disease. The clinical characteristics of the patients were as expected, with high International Prognostic Index scores, elevated serum lactate dehydrogenase (LDH) levels, and bulky disease being adverse prognostic factors. Only 6 patients (25%) showed CD30 expression, and Bcl-6 protein expression was, in our series, prognostically favorable (P = .0401). One patient's tumor had detectable HHV-6 genome sequence, but no HHV-8 sequences were detected in any tumors. Two thirds of the patients received CHOP chemotherapy (cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone) with a relatively low complete remission rate (43.8%; median follow-up, 33.8 months). This study confirmed the moderate preponderance among PMLBCL patients of young females with B symptoms and elevated LDH levels. The CHOP regimen proved effective as first-line therapy only in patients with limited disease. Therefore, other third-generation chemotherapy protocols may be considered for treatment, especially in patients with bulky and advanced disease.
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