Robert Stapp

Aurora A is differentially expressed in gliomas, is associated with patient survival in glioblastoma, and is a potential chemotherapeutic target in gliomas

Aurora A is critical for mitosis and is overexpressed in several neoplasms. Its overexpression transforms cultured cells, and both its overexpression and knockdown cause genomic instability. In transgenic mice, Aurora A haploinsufficiency, not overexpression, leads to increased malignant tumor formation. Aurora A thus appears to have both tumor-promoting and tumor-suppressor functions. Here, we report that Aurora A protein, measured by quantitative protein gel blotting, is differentially expressed in major glioma types in lineage-specific patterns. Aurora A protein levels in WHO grade II oligodendrogliomas (n = 16) and grade III anaplastic oligodendrogliomas (n = 16) are generally low, similar to control epilepsy cerebral tissue (n = 11). In contrast, pilocytic astrocytomas (n = 6) and ependymomas (n = 12) express high Aurora A levels. Among grade II to grade III astrocytomas (n = 7, n = 14, respectively) and grade IV glioblastomas (n = 31), Aurora A protein increases with increasing tumor grade. We also found that Aurora A expression is induced by hypoxia in cultured glioblastoma cells and is overexpressed in hypoxic regions of glioblastoma tumors. Retrospective Kaplan-Meier analysis revealed that both lower Aurora A protein measured by quantitative protein gel blot (n = 31) and Aurora A mRNA levels measured by real-time quantitative RT-PCR (n = 58) are significantly associated with poorer patient survival in glioblastoma. Furthermore, we report that the selective Aurora A inhibitor MLN8237 is potently cytotoxic to glioblastoma cells, and that MLN8237 cytotoxicty is potentiated by ionizing radiation. MLN8237 also appeared to induce senescence and differentiation of glioblastoma cells. Thus, in addition to being significantly associated with survival in glioblastoma, Aurora A is a potential new drug target for the treatment of glioblastoma and possibly other glial neoplasms.

The Usefulness of IgG and IgM Immunostaining of Periportal Inflammatory Cells (Plasma Cells and Lymphocytes) for the Distinction of Autoimmune Hepatitis and Primary Biliary Cirrhosis and Their Staining Pattern in Autoimmune Hepatitis–Primary Biliary Cirrhosis Overlap Syndrome

Autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome (OS) is a vaguely defined entity demonstrating features of AIH and PBC. We investigated the usefulness of IgG and IgM immunostaining for the distinction of AIH and PBC and their staining pattern in cases of possible OS. The approximate quantity of IgG+ and IgM+ periportal inflammatory cells in immunohistochemical analysis were compared in cases of AIH, PBC, and OS. AIH cases showed predominant IgG immunostaining of periportal inflammatory cells. A significant number of PBC cases also demonstrated IgG predominance rather than IgM. Six OS cases had IgG predominance, 4 had IgM predominance, and 1 was equivocal. The usefulness of IgG and IgM immunostaining is limited in PBC cases with IgM predominance for excluding AIH. IgG predominance is not specific for AIH. OS does not demonstrate either IgG or IgM predominance (P > .2) and does not help classify OS into either category.

Osteocutaneous radial forearm reconstruction of large partial cricotracheal defects.

Single‐stage procedures for reconstruction of large cricotracheal defects have been limited in success and malignant immature teratomas in the larynx of an adult have never been reported.

Review of Cytology Practice at Thomas Jefferson University Hospital before and after High-Risk Human Papillomavirus Testing

Objective: We performed a retrospective review of Papanicolaou (Pap) testing to assess whether the cytology practice in our institution was affected by the introduction of high-risk (HR) human papillomavirus (HPV) assays over time. Study Design: Cytology, HPV and histopathology records were retrieved from our laboratory information system from 2003 to 2015. Records for Digene Hybrid Capture 2®, Hologic Cervista® and Roche Cobas® HPV assays were obtained. A 3-month follow-up for HPV detected cases was performed, and results were correlated with cytology and biopsies. A 1-year follow-up of HPV 16/18 and other HR HPV detected cases was also performed. Results: From 2008 to 2015, a noticeable decrease in Pap testing volume occurred, from 11,792 to 4,664, while the percentage of HPV testing increased from 19 to 59%. Similar HPV detection rates and follow-up results for both reflex and cotesting were observed in the 3 HPV assays. Conclusions: The decrease in Pap testing was due to the lengthening of the test interval when cotesting results were negative. Practitioners adhering to guidelines accounts for increased molecular testing volume. A trend towards higher-grade cervical intraepithelial neoplasia in the follow-up of detected HPV 16/18 was noted. So far there has been no demand for HPV as a stand-alone test.

Immunohistochemical Staining of Inflammatory Cells in Liver Biopsy Specimens of Patients With Autoimmune Hepatitis, Primary Biliary Cirrhosis, and Overlap SyndromesThe Authors’ Reply

To the Editor I read with great interest the study by Lee et al1 evaluating IgG and IgM immunohistochemical staining of inflammatory cells in liver biopsy specimens of patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and overlap syndromes. The authors report an IgG-predominant infiltrate in all cases of AIH. However, a large proportion (12/26) of PBC cases also showed a predominantly IgG+ infiltrate, which would potentially decrease the usefulness of IgM and IgG immunohistochemical staining in this setting. In contrast with these results, Daniels et al2 reported IgG-predominant infiltrates in all cases of AIH (n = 38) and IgM-predominant infiltrates in the vast majority (16/18 [89%]) of PBC cases. Similarly, our group recently published a study3 evaluating IgM and IgG immunohistochemical staining in various forms of liver disease, including AIH, PBC, primary sclerosing cholangitis …

VOLUNTARY IMPORT EXPANSION AND DIRECT INVESTMENT

This paper analyses the welfare effects of a market-share Voluntary Import Expansion (VIE) in the presence of foreign direct investment utilizing a duality approach. Introducing the cost burden of VIE explicitly, this paper considers the conditions under which a market-share VIE is voluntary to the importing country. It is shown that the voluntary nature of VIE depends upon the capital import, cost burden and price difference effects and that a VIE is truly voluntary if it is accompanied by direct investment. We also show the existence of a complementary relationship between VIE and direct investment in attaining a particular level of welfare.

On the new export sector in developing countries

Abstract Many developing countries are establishing a new export sector by accepting foreign direct investment. Developing a three-sectors three-factors general equilibrium model with tariff, this paper considers the condition under which the acceptance of direct investment is desirable for the developing countries. We show that the factor intensity rankings among the sectors play a key role on the welfare effects and that direct investment increases the output of both the new export and the traditional export sector and promotes the export-led growth in developing countries.

Labor importation and immiserizing growth

Abstract To accommodate for the labor importation of developed countries in recent years, this paper extends the analyses of immiserizing growth to the case of labor importation with three sectors model including the non-traded goods. We derive the effects of labor importation on factor rewards, outputs, and welfare and it will be shown that the effect of labor importation on welfare can be divided into four aspects. The possibility of immiserization still exists in our model.