Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with suspected ovarian cancer.

As a promoter of angiogenesis, vascular endothelial growth factor (VEGF) is believed to play a pivotal role in tumour growth and metastasis. The aim of this study was to determine the value of preoperative serum VEGF levels in the early diagnosis of ovarian cancer and in the differential diagnosis of adnexal masses. We examined preoperative serum VEGF levels in healthy women (n = 131), patients with benign ovarian cysts (n = 81) and in ovarian cancer patients (n = 44) by using an ELISA (R&D Systems, Minneapolis, MN, USA). A logistic regression model was carried out to determine the influence of VEGF and CA 125 on the probability of malignancy. VEGF revealed a significant influence on the odds of presenting with malignancy vs healthy women (P = 0.001). At 363.7 pg ml(-1), VEGF achieved a sensitivity of 54% and a specificity of 77%. With respect to the differentiation between benign cysts and ovarian cancer, CA 125 (P < 0.0001) but not VEGF (P = 0.229) predicts the presence of malignancy in a multivariate model. In conclusion, VEGF does not appear to be a useful tool in the early diagnosis of ovarian cancer or for indicating the absence or presence of malignancy in patients with an adnexal mass

Unifying the Phase Diagrams of the Magnetic and Transport Properties of La_(2-x)Sr_xCuO_4, 0 < x < 0.05

An extensive experimental and theoretical effort has led to a largely complete mapping of the magnetic phase diagram of La_(2-x)Sr_xCuO_4, and a microscopic model of the spin textures produced in the x < 0.05 regime has been shown to be in agreement with this phase diagram. Here we use this same model to derive a theory of the impurity-dominated, low temperature transport. Then, we present an analysis of previously published data for two samples: x = 0.002 data from Chen et. al., and x = 0.04 data from Keimer et. al. We show that the transport mechanisms in the two systems are the same, even though they are on opposite sides of the observed insulator-to-metal transition. Our model of impurity effects on the impurity band conduction, variable-range hopping conduction, and coulomb gap conduction, is similar to that used to describe doped semiconductors. However, for La_(2-x)Sr_xCuO_4 we find that in addition to impurity-generated disorder effects, strong correlations are important and must be treated on a equal level with disorder. On the basis of this work we propose a phase diagram that is consistent with available magnetic and transport experiments, and which connects the undoped parent compound with the lowest x value for which La_(2-x)Sr_xCuO_4 is found to be superconducting, x about 0.06.Comment: 7 pages revtex with one .ps figur

The Victorian Newsletter (Spring 1975)

The Victorian Newsletter is sponsored for the English X Group of the Modern Language Association by New York University and Queens College, City University of New York.The Forms of Victorian Fiction / James R. Kincaid -- Method and Moral in George Eliot's Narrative / Elizabeth Ermarth -- Vision and Form: The English Novel and the Emergence of the Short Story / Wendell V. Harris -- Progressive Dubiety: The Discontinuity of Disraeli's Political Trilogy / Daniel R. Schwarz -- Pater's Conception of the Renaissance: From Sources to Personal Ideal / Billie Andrew Inman -- Critical Forum / G. B. Tennyson, Robert O. Preyer, James G. Nelson, and Phyllis Grosskurth -- Recent Publications: A Selected List / Arthur F. Minerof -- English X New

Interplay between Kinase Domain Autophosphorylation and F-Actin Binding Domain in Regulating Imatinib Sensitivity and Nuclear Import of BCR-ABL

BACKGROUND: The constitutively activated BCR-ABL tyrosine kinase of chronic myeloid leukemia (CML) is localized exclusively to the cytoplasm despite the three nuclear localization signals (NLS) in the ABL portion of this fusion protein. The NLS function of BCR-ABL is re-activated by a kinase inhibitor, imatinib, and in a kinase-defective BCR-ABL mutant. The mechanism of this kinase-dependent inhibition of the NLS function is not understood. METHODOLOGY/PRINCIPAL FINDINGS: By examining the subcellular localization of mutant BCR-ABL proteins under conditions of imatinib and/or leptomycin B treatment to inhibit nuclear export, we have found that mutations of three specific tyrosines (Y232, Y253, Y257, according to ABL-1a numbering) in the kinase domain can inhibit the NLS function of kinase-proficient and kinase-defective BCR-ABL. Interestingly, binding of imatinib to the kinase-defective tyrosine-mutant restored the NLS function, suggesting that the kinase domain conformation induced by imatinib-binding is critical to the re-activation of the NLS function. The C-terminal region of ABL contains an F-actin binding domain (FABD). We examined the subcellular localization of several FABD-mutants and found that this domain is also required for the activated kinase to inhibit the NLS function; however, the binding to F-actin per se is not important. Furthermore, we found that some of the C-terminal deletions reduced the kinase sensitivity to imatinib. CONCLUSIONS/SIGNIFICANCE: Results from this study suggest that an autophosphorylation-dependent kinase conformation together with the C-terminal region including the FABD imposes a blockade of the BCR-ABL NLS function. Conversely, conformation of the C-terminal region including the FABD can influence the binding affinity of imatinib for the kinase domain. Elucidating the structural interactions among the kinase domain, the NLS region and the FABD may therefore provide insights on the design of next generation BCR-ABL inhibitors for the treatment of CML

Neural Basis of Self and Other Representation in Autism: An fMRI Study of Self-Face Recognition

Autism is a developmental disorder characterized by decreased interest and engagement in social interactions and by enhanced self-focus. While previous theoretical approaches to understanding autism have emphasized social impairments and altered interpersonal interactions, there is a recent shift towards understanding the nature of the representation of the self in individuals with autism spectrum disorders (ASD). Still, the neural mechanisms subserving self-representations in ASD are relatively unexplored.We used event-related fMRI to investigate brain responsiveness to images of the subjects' own face and to faces of others. Children with ASD and typically developing (TD) children viewed randomly presented digital morphs between their own face and a gender-matched other face, and made "self/other" judgments. Both groups of children activated a right premotor/prefrontal system when identifying images containing a greater percentage of the self face. However, while TD children showed activation of this system during both self- and other-processing, children with ASD only recruited this system while viewing images containing mostly their own face.This functional dissociation between the representation of self versus others points to a potential neural substrate for the characteristic self-focus and decreased social understanding exhibited by these individuals, and suggests that individuals with ASD lack the shared neural representations for self and others that TD children and adults possess and may use to understand others

Angiogenesis in cervical carcinoma

Angiogenesis means the formation of new blood vessels and it is considered a critical step for the growth of solid tumours. Angiogenic factors (AF), such as vascular endothelial growth factor (VEGF) are released by tumour cells and induce the formation of a dense capillary net, which surrounds the tumour. Microvessel density (MVD) is regarded a measure for tumour angiogenesis and has been found to be prognostically significance in many tumour types. In this summary we review the evidence for the prognostic significance of angiogenesis and hypoxia in cervical cancer