Hemostatic gene polymorphisms and the prevalence of thrombotic complications in polycythemia vera and essential thrombocythemia.

Patients with polycythemia vera and essential thrombocythemia are at risk for thrombotic and bleeding complications. Currently, no diagnostic test can predict thrombohemorrhagic complications. In a prospective study of 86 patients with polycythemia vera (43 patients) or essential thrombocythemia (43 patients), we examined the possible role of polymorphisms of platelet adhesion receptors [glycoprotein (GP) Ibalpha, GPIa, GPIIIa) and clotting factor II (prothrombin's G20210A mutation) and clotting factor V (Leiden mutation) in determining the risk of thrombotic or bleeding complications. Except for an association between vasomotor symptoms and prothrombin mutation (P < 0.001), no significant correlation between polymorphism of clotting factors and thrombohemorrhagic complications was identified. When the entire patient cohort was considered, the polymorphisms of platelet adhesion receptors were not associated with the risk for thrombotic or bleeding complications. However, among patients with polycythemia vera, the presence of the PlA2 allele of GPIIIa was associated with an increased risk of arterial thrombosis. In view of previous studies linking the presence of the PlA2 allele of GPIIIa to a higher risk for coronary artery thrombosis, our data have physiologic relevance. However, they need to be confirmed in a larger study.     

BRAF and NRAS Mutations Are Frequent in Nodular Melanoma but Are not Associated with Tumor Cell Proliferation or Patient Survival

Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.     

Significance of Charcot Leyden crystals in liver cytology—A case report

Charcot Leyden crystals are colorless, hexagonal, bipyramidal crystals formed from aggregation of material from disintegrating eosinophils. Eosinophilic infiltrate along with the presence of Charcot Leyden crystals is an indirect evidence of parasitic infestation. Here, we report a case where fine‐needle aspiration cytology smears prepared from hepatic space occupying lesion showed numerous Charcot Leyden crystals along with eosinophilic infiltrate, indicating parasitic infection. Diagn. Cytopathol. 2015;43:392–394. © 2014 Wiley Periodicals, Inc.     

Larvicidal and pupicidal activities of ecbolin A and ecbolin B isolated from Ecbolium viride (Forssk.) Alston against Culex quinquefasciatus Say (Diptera: Culicidae)

The mosquitocidal activity of different fractions and isolated compounds from the ethyl acetate extract of Ecbolium viride root was assessed on larvae and pupae of Culex quinquefasciatus Say (Diptera: Culicidae). The larvae and pupae were exposed to concentrations of 6.125, 12.5, 25 and 50 ppm for fractions and 1, 2.5, 5 and 10 ppm for compound. Among the 12 fractions screened, fraction 6 from the ethyl acetate extract of E. viride was recorded to have the highest larvicidal and pupicidal activities against C. quinquefasciatus. The lethal concentration (LC₅₀ and LC₉₀) values of fraction 6 were 4.26 and 9.0 ppm against C. quinquefasciatus larvae and 6.55 and 12.19 ppm against C. quinquefasciatus pupae, respectively, in 24 h. Fraction 7 was recorded to have moderate activity with LC₅₀ and LC₉₀ values of 11.25 and 25.02 ppm against C. quinquefasciatus larvae and 13.33 and 31.15 ppm against C. quinquefasciatus pupae, respectively, in 24 h. Ecbolin A and ecbolin B were identified from fractions 7 and 6, respectively. The structure of the isolated compounds was identified on the basis of spectral data (¹H NMR and ¹³C NMR) and compared with literature spectral data. Further, the isolated compound, ecbolin B, from fraction 6 was recorded to have strong larvicidal and pupicidal activities than ecbolin A. The LC₅₀ and LC₉₀ values of ecbolin B on C. quinquefasciatus larvae were 1.36 and 2.76 ppm, and on pupae, these were 1.54 and 3.51 ppm, respectively. The present results suggest that ecbolin B could be used as a mosquitocidal agent against C. quinquefasciatus.     

CD81-Receptor Associations — Impact for Hepatitis C Virus Entry and Antiviral Therapies

Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into host cells, including hepatitis C virus (HCV) entry into hepatocytes. HCV is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV entry into hepatocytes is a complex process that requires the coordinated interaction of viral and host factors for the initiation of infection, including CD81, scavenger receptor BI, claudin-1, occludin, membrane-bound host cell kinases, Niemann-Pick C1 Like 1, Harvey rat sarcoma viral oncogene homolog (HRas), CD63 and transferrin receptor 1. Furthermore, recent data in HCV model systems have demonstrated that targeting critical components of tetraspanins and associated cell membrane proteins open new avenues to prevent and treat viral infection.