bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration of the Direct Use of Anodized Alumina as a Mold for Nanoimprint Lithography to Fabricate Magnetic Nanostructure over Large Area
Authors: Rahman M. Tofizur , Wang Hao , Wang Jian-Ping
Published: November 2011

We have explored the direct use of anodized alumina (AAO) fabricated on an Si wafer as a mold for the nanoimprint lithography (NIL). The AAO mold has been fabricated over more than 10 cm2area with two different pore diameters of163±24 nm and73±7 nm. One of the key challenges of the lack of bonding between the antisticking self-assembled monolayer (SAM) and the AAO has been overcome by modifying the surface chemistry of the fabricated AAO mold by coating it with thin SiO2layer. Then we have applied the commonly used silane-based self-assembled monolayer (SAM) on these SiO2-coated AAO molds and achieved successful imprinting of resist pillars with feature size of172±25 nm by using the mold with a pore diameter of163±24 nm. Finally, we have achieved (001) oriented L10FePt patterned structure with a dot diameter of42±4 nm by using a AAO mold with a pore diameter of73±7 nm. The perpendicularHcof the unpatterned and patterned FePt is about 3.3 kOe and 12 kOe, respectively. These results indicate that AAO mold can potentially be used in NIL for fabricating patterned nanostructures over large area.
Public Housing Construction and the Cities: 1937–1967
Authors: McDonald John F.
Published: November 2011

Public housing advocates argue that the nation should expand the federal public housing program as part of an effort to increase the supply of affordable rental housing. This paper examines federal public housing construction in the largest US cities over the period 1937–1967, a period during which the public housing program was the primary program to provide low‐income households with affordable rental housing. Public housing is found to depend upon the population level of the city, factors that characterize the housing stock as of 1950, the poverty level in the city, and the size of the nonwhite population in the city. The National Commission on Urban Problems (National commission on urban problems 1968, page 128) found that this supply response meant that “… the great need of the large central cities for housing for poor families was largely unmet.” Changes in racial segregation from 1940 to 1960 are found to be unrelated to public housing construction. While the current situation is different in many respects from circumstances of these earlier decades, a renewed effort to supply public housing might produce similar outcomes.
Management of High-Risk Localized Prostate Cancer
Authors: Marciscano Ariel E. , Hardee Matthew E. , Sanfilippo Nicholas
Published: November 2011

Traditionally, patients with high-risk localized prostate cancer have been an extremely challenging group to manage due to a significant likelihood of treatment failure and prostate cancer-specific mortality (PCSM). The results of multiple large, prospective, randomized trials have demonstrated that men with high-risk features who are treated in a multimodal fashion at the time of initial diagnosis have improved overall survival. Advances in local treatments such as dose-escalated radiotherapy in conjunction with androgen suppression and postprostatectomy adjuvant radiotherapy have also demonstrated benefits to this subset of patients. However, therapeutic enhancement with the addition of chemotherapy to the primary treatment regimen may help achieve optimal disease control.
Atypical Clinical Manifestations of Graves' Disease: An Analysis in Depth
Authors: Hegazi Mohamed Osama , Ahmed Sherif
Published: November 2011

Over the past few decades, there has been an increase in the number of reports about newly recognized (atypical or unusual) manifestations of Graves' disease (GD), that are related to various body systems. One of these manifestations is sometimes the main presenting feature of GD. Some of the atypical manifestations are specifically related to GD, while others are also similarly seen in patients with other forms of hyperthyroidism. Lack of knowledge of the association between these findings and GD may lead to delay in diagnosis, misdiagnosis, or unnecessary investigations. The atypical clinical presentations of GD include anemia, vomiting, jaundice, and right heart failure. There is one type of anemia that is not explained by any of the known etiological factors and responds well to hyperthyroidism treatment. This type of anemia resembles anemia of chronic disease and may be termed GD anemia. Other forms of anemia that are associated with GD include pernicious anemia, iron deficiency anemia of celiac disease, and autoimmune hemolytic anemia. Vomiting has been reported as a presenting feature of Graves' disease. Some cases had the typical findings of hyperthyroidism initially masked, and the vomiting did not improve until hyperthyroidism has been detected and treated. Hyperthyroidism may present with jaundice, and on the other hand, deep jaundice may develop with the onset of overt hyperthyroidism in previously compensated chronic liver disease patients. Pulmonary hypertension is reported to be associated with GD and to respond to its treatment. GD-related pulmonary hypertension may be so severe to produce isolated right-sided heart failure that is occasionally found as the presenting manifestation of GD.
Intervention to Prevent Child Custody Loss in Mothers with Schizophrenia
Authors: Seeman Mary V.
Published: November 2011

Depending on jurisdiction, time period studied, and specifics of the population, approximately 50 percent of mothers who suffer from schizophrenia lose custody of their children. The aim of this paper is to recommend interventions aimed at preventing unnecessary custody loss. This paper reviews the social work, nursing, psychology, psychiatry, and law literature on mental illness and custody loss, 2000–2011. Recommendations to mothers are to (a) ensure family health (b) prevent psychotic relapse, (c) prepare in advance for crisis, (d) document daily parenting activities, (e) take advantage of available parenting resources, and f) become knowledgeable about legal issues that pertain to mental health and custody. From a policy perspective, child protection and adult mental health agencies need to dissolve administrative barriers and collaborate. Access to appropriate services will help mothers with schizophrenia to care appropriately for their children and allow these children to grow and develop within their family and community.
Mechanisms of Edible Bird's Nest Extract-Induced Proliferation of Human Adipose-Derived Stem Cells
Authors: Roh Kyung-Baeg , Lee Jienny , Kim Young-Soo , Park Junho , Kim Jang-Hyun , Lee Jongsung , Park Deokhoon
Published: November 2011

Although edible bird's nest (EBN) has been shown to potentiate mitogenic responses, scientific evidence of its efficacy is still limited. In addition, human adipose-derived stem cells (hADSCs) are increasingly accepted as a source for stem cell therapy. Therefore, the aim of this study was to investigate the effects of the EBN extract (EBNE) on the proliferation of hADSCs and its action mechanisms. We found that EBNE strongly promoted the proliferation of hADSCs. In addition, EBNE-induced proliferation was found to be mediated through the production of IL-6 and VEGF, which was induced by activation of AP-1 and NF-κB. Specially, we found that production of IL-6 and VEGF was induced by EBNE. In addition, EBNE-induced production of IL-6 and VEGF was inhibited by PD98059 (a p44/42 MAPK inhibitor), SB203580 (a p38 MAPK inhibitor), and PDTC (a NF-κB inhibitor), but not SP600125 (a JNK inhibitor). Similarly, EBNE-induced proliferation of hADSCs was also attenuated by PD98059, SB203580, and PDTC but not SP600125. Taken together, these findings suggest that the EBNE-induced proliferation of hADSCs primarily occurs through increased expression of IL-6 and VEGF genes, which is mediated by the activation of NF-κB and AP-1 through p44/42 MAPK and p38 MAPK.
Dual IGF-1R/InsR Inhibitor BMS-754807 Synergizes with Hormonal Agents in Treatment of Estrogen-Dependent Breast Cancer
Authors: Hou Xiaonan , Huang Fei , Macedo Luciana F. , Harrington Sean C. , Reeves Karen A. , Greer Ann , Finckenstein Friedrich Graf , Brodie Angela , Gottardis Marco M. , Carboni Joan M. , Haluska Paul
Published: November 2011

Insulin-like growth factor (IGF) signaling has been implicated in the resistance to hormonal therapy in breast cancer. Using a model of postmenopausal, estrogen-dependent breast cancer, we investigated the antitumor effects of the dual IGF-1R/InsR tyrosine kinase inhibitor BMS-754807 alone and in combination with letrozole or tamoxifen. BMS-754807 exhibited antiproliferative effects in vitro that synergized strongly in combination with letrozole or 4-hydroxytamoxifen and fulvestrant. Similarly, combined treatment of BMS-754807 with either tamoxifen or letrozole in vivo elicited tumor regressions not achieved by single-agent therapy. Notably, hormonal therapy enhanced the inhibition of IGF-1R/InsR without major side effects in animals. Microarray expression analysis revealed downregulation of cell-cycle control and survival pathways and upregulation of erbB in response to BMS-754807 plus hormonal therapy, particularly tamoxifen. Overall, these results offer a preclinical proof-of-concept for BMS-754807 as an antitumor agent in combination with hormonal therapies in hormone-sensitive breast cancer. Cooperative cell-cycle arrest, decreased proliferation, and enhanced promotion of apoptosis may contribute to antitumor effects to be gauged in future clinical investigations justified by our findings. Cancer Res; 71(24); 7597–607. ©2011 AACR.
In Vivo Magnetic Resonance Imaging of the Estrogen Receptor in an Orthotopic Model of Human Breast Cancer
Authors: Pais Adi , Gunanathan Chidambaram , Margalit Raanan , Eti Biton Inbal , Yosepovich Ady , Milstein David , Degani Hadassa
Published: November 2011

Histologic overexpression of the estrogen receptor α (ER) is a well-established prognostic marker in breast cancer. Noninvasive imaging techniques that could detect ER overexpression would be useful in a variety of settings where patients' biopsies are problematic to obtain. This study focused on developing, by in vivo MRI, strategies to measure the level of ER expression in an orthotopic mouse model of human breast cancer. Specifically, novel ER-targeted contrast agents based on pyridine-tetra-acetate-Gd(III) chelate (PTA-Gd) conjugated to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd) were examined in ER-positive or ER-negative tumors. Detection of specific interactions of EPTA-Gd with ER were documented that could differentiate ER-positive and ER-negative tumors. In vivo competition experiments confirmed that the enhanced detection capability of EPTA-Gd was based specifically on ER targeting. In contrast, PTA-Gd acted as an extracellular probe that enhanced ER detection similarly in either tumor type, confirming a similar vascular perfusion efficiency in ER-positive and ER-negative tumors in the model. Finally, TPTA-Gd accumulated selectively in muscle and could not preferentially identify ER-positive tumors. Together, these results define a novel MRI probe that can permit selective noninvasive imaging of ER-positive tumors in vivo. Cancer Res; 71(24); 7387–97. ©2011 AACR.
Angiopoietin-like Protein 2 Is an Important Facilitator of Inflammatory Carcinogenesis and Metastasis
Authors: Aoi Jun , Endo Motoyoshi , Kadomatsu Tsuyoshi , Miyata Keishi , Nakano Masahiro , Horiguchi Haruki , Ogata Aki , Odagiri Haruki , Yano Masato , Araki Kimi , Jinnin Masatoshi , Ito Takaaki , Hirakawa Satoshi , Ihn Hironobu , Oike Yuichi
Published: November 2011

Chronic inflammation plays important roles at different stages of cancer development, including carcinogenesis, tumor invasion, and metastasis, but molecular mechanisms linking inflammation to cancer development have not been fully clarified. Here, we report that expression of angiopoietin-like protein 2 (Angptl2), recently identified as a chronic inflammation mediator, is highly correlated with the frequency of carcinogenesis in a chemically induced skin squamous cell carcinoma (SCC) mouse model. Furthermore, Angptl2 expression in SCC is highly correlated with the frequency of tumor cell metastasis to distant secondary organs and lymph nodes. When SCC was induced in transgenic mice expressing Angptl2 in skin epithelial cells, epithelial-to-mesenchymal transitions in SCC as well as tumor angiogenesis and lymphangiogenesis were significantly increased, resulting in increased tumor cell metastasis and shortened survival compared with wild-type mice. Conversely, in a chemically induced SCC mouse model, carcinogenesis and metastasis were markedly attenuated in Angptl2 knockout mice, resulting in extended survival compared with wild-type mice. Overall, we propose that Angptl2 contributes to increased carcinogenesis and metastasis and represents a novel target to antagonize these pathologies. Cancer Res; 71(24); 7502–12. ©2011 AACR.
Finding a Panacea among Combination Cancer Therapies
Authors: Yamaguchi Ryuji , Perkins Guy
Published: November 2011

Because each cancer is a heterogeneous mix of cancer cells at different stages of development, we are faced with trying to treat many different diseased cells all at once. An authentic approach is to build a genomic and proteomic profile of a patient, identify the target oncogenes, and prescribe the combination of targeted drugs tailored for that patient. However, there are many practical problems with this personalized medicine approach: (i) cancers often generate treatment-resistant phenotypes, (ii) the treatment could be enormously expensive, and (iii) most of the targeted drugs have not been developed yet. We propose a different approach: therapies that combine 2-deoxyglucose (2DG) with Bcl-2 antagonist such as ABT-263/737 (ABT). Proapoptotic protein Bak is normally sequestered by Mcl-1 and Bcl-xL. Only when Bak is released from both Mcl-1 and Bcl-xL can it induce apoptosis. 2DG can prime highly glycolytic cells by dissociating Bak-Mcl-1 complex. Some brain cells and most cancer cells are primed by 2DG. ABT can bind to Bcl-xL, dissociating Bak-Bcl-xL complex, freeing Bak and inducing apoptosis. Because ABT cannot cross blood–brain barrier, the only cells exposed to both agents are highly glycolytic cancer cells located outside the brain. Because ABT directly triggers apoptosis at the step very near the terminal point of apoptosis, 2DG-ABT combination therapies are applicable to many types of cancer at all stages of development, with little side effect. Cancer Res; 72(1); 18–23. ©2011 AACR.
2-(3-{1-Carboxy-5-[(6-[18F]Fluoro-Pyridine-3-Carbonyl)-Amino]-Pentyl}-Ureido)-Pentanedioic Acid, [18F]DCFPyL, a PSMA-Based PET Imaging Agent for Prostate Cancer
Authors: Chen Ying , Pullambhatla Mrudula , Foss Catherine A. , Byun Youngjoo , Nimmagadda Sridhar , Senthamizhchelvan Srinivasan , Sgouros George , Mease Ronnie C. , Pomper Martin G.
Published: November 2011

Purpose: We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, as a potential imaging agent for the prostate-specific membrane antigen (PSMA). PSMA is upregulated in prostate cancer epithelia and in the neovasculature of most solid tumors.

Experimental Design: [18F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[18F]fluoronicotinic acid tetrafluorophenyl ester ([18F]F-Py-TFP) for introduction of 18F. Radiochemical synthesis was followed by biodistribution and imaging with PET in immunocompromised mice using isogenic PSMA PC3 PIP and PSMA- PC3 flu xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0.

Results: DCFPyL displays a Ki value of 1.1 ± 0.1 nmol/L for PSMA. [18F]DCFPyL was produced in radiochemical yields of 36%–53% (decay corrected) and specific radioactivities of 340–480 Ci/mmol (12.6–17.8 GBq/μmol, n = 3). In an immunocompromised mouse model [18F]DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 hours postinjection, 39.4 ± 5.4 percent injected dose per gram of tissue (%ID/g) was evident within the PSMA+ PC3 PIP tumor, with a ratio of 358:1 of uptake within PSMA+ PC3 PIP to PSMA− PC3 flu tumor placed in the opposite flank. At or after 1 hour postinjection, minimal nontarget tissue uptake of [18F]DCFPyL was observed. The bladder wall is the dose-limiting organ.

Conclusions: These data suggest [18F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues. Clin Cancer Res; 17(24); 7645–53. ©2011 AACR.
Vibrio cholerae Typing Phage N4: Genome Sequence and Its Relatedness to T7 Viral Supergroup
Authors: Das Mayukh , Nandy R.K. , Bhowmick Tushar Suvra , Yamasaki S. , Ghosh A. , Nair G.B. , Sarkar B.L.
Published: November 2011

Objectives: In countries where cholera is endemic, Vibrio cholerae O1 bacteriophages have been detected in sewage water. These have been used to serve not only as strain markers, but also for the typing of V. cholerae strains. Vibriophage N4 (ATCC 51352-B1) occupies a unique position in the new phage-typing scheme and can infect a larger number of V. cholerae O1 biotype El Tor strains. Here we characterized the complete genome sequence of this typing vibriophage. Methods: The complete DNA sequence of the N4 genome was determined by using a shotgun sequencing approach. Results: Complete genome sequence explored that phage N4 is comprised of one circular, double-stranded chromosome of 38,497 bp with an overall GC content of 42.8%. A total of 47 open reading frames were identified and functions could be assigned to 30 of them. Further, a close relationship with another vibriophage, VP4, and the enterobacteriophage T7 could be established. DNA-DNA hybridization among V. cholerae O1 and O139 phages revealed homology among O1 vibriophages at their genomic level. Conclusions: This study indicates two evolutionary distinctive branches of the possible phylogenetic origin of O1 and O139 vibriophages and provides an unveiled collection of information on viral gene products of typing vibriophages.
Amino Acid Substitution in HCV Core Region and Genetic Variation near the IL28B Gene Affect Viral Dynamics during Telaprevir, Peginterferon and Ribavirin Treatment
Authors: Akuta Norio , Suzuki Fumitaka , Hirakawa Miharu , Kawamura Yusuke , Yatsuji Hiromi , Sezaki Hitomi , Suzuki Yoshiyuki , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Chayama Kazuaki , Nakamura Yusuke , Kumada Hiromitsu
Published: November 2011

Objectives: Genetic variation near the IL28B gene and substitution of aa 70 and 91 in the core region of HCV-1b are useful as predictors of treatment efficacy to telaprevir/pegylated interferon (PEG-IFN)/ribavirin, but its impact on viral dynamics is not clear. Methods: This study investigated predictive factors of viral dynamics during 12- or 24-week regimen of triple therapy in 80 Japanese adults infected with HCV-1b. Results: After 24 h of commencement of treatment, the proportion of patients with Arg70 and Leu91 substitutions in the core region who showed ≥3.0 log drop in HCV RNA level was significantly higher than that of patients with Gln70 (His70) and/or Met91. At 8 and 12 weeks, HCV RNA loss rate of patients with rs8099917 genotype TT near IL28B gene was significantly higher than that of patients with non-TT. Multivariate analysis identified substitution of aa 70 and 91 as a predictor of ≥3.0 log fall in HCV RNA level at 24 h (Arg70 and Leu91) and SVR (Arg70), and rs8099917 (TT) as a predictor of HCV RNA loss at 12 weeks and SVR. Conclusions: This study identified genetic variation near IL28B gene and aa substitution of the core region as predictors of viral dynamics during triple therapy.
Foreign Gene Transfer to Cardiomyocyte Using a Replication-Defective Recombinant Coxsackievirus B3 without Cytotoxicity
Authors: Lim Byung-Kwan , Yun Soo-Hyeon , Gil Chae-Ok , Ju Eun-Seon , Choi Jin-Oh , Kim Duk-Kyung , Jeon Eun-Seok
Published: November 2011

Background: Replication-competent coxsackievirus B3 (CVB3) has been used as a gene transfer vector for cultured cardiomyocytes and hearts in vivo. However, CVB3 induces cell lysis when it replicates in infected cells. In this study, we investigated whether a replication-defective rCVB3 vector could be generated and used as a noncytotoxic gene transfer vector for cardiomyocytes. Methods: We generated a replication-defective luciferase-expressing CVB3 plasmid. This recombinant cDNA and pCMV-P1 plasmids were amplified and cotransfected into Hek293 cells using transfection reagents. Replication-defective rLuCVB3 virus was recovered from the cells and cell culture supernatants for 3 days after transfection. The generated rLuCVB3 viruses were concentrated on a 30% sucrose cushion and semiquantified using a luciferase assay. In addition, foreign gene delivery by the rLuCVB3 was tested in cultured cardiomyocytes and intact mouse hearts after rLuCVB3 infection. Results: Luciferase was expressed in Hek293, HeLa cells and cardiomyocytes after rLuCVB3 infection. In addition, these cells did not show a significant cytopathic effect after 72 h. Luciferase protein expression or activity were detected for 3 days in the myocardium of rLuCVB3-infected mouse hearts without producing cytotoxicity or inflammation. Conclusion: As a proof-of-concept, these data indicate that a replication-defective rCVB3 vector can be generated and used as a novel gene transfer system to transfect exogenous genes into cardiomyocytes without generating cytotoxicity.
A Short Hairpin Loop-Structured Oligodeoxynucleotide Targeting the Virion-Associated RNase H of HIV Inhibits HIV Production in Cell Culture and in huPBL-SCID Mice
Authors: Heinrich Jochen , Schols Dominique , Moelling Karin
Published: November 2011

Background: We have recently demonstrated that an oligodeoxynucleotide (ODN) can enter HIV particles and form a local hybrid at the highly conserved polypurine tract (PPT), the target site of the ODN. This hybrid is recognized by the retrovirus-specific RNase H, which is a virion-associated enzyme. It cleaves the RNA at local hybrids and thereby destroys viral infectivity. This mechanism has been described previously in a mouse model using an oncogenic retrovirus and was commented as driving HIV into suicide. The RNase H is one of four retrovirus-specific enzymes and not yet targeted by antiviral drugs. Aims: We wanted to analyze the tendency of ODNs to induce mutations in cell culture and its efficacy to inhibit HIV in humanized SCID mice. Method: We used cultures of CD4+ T cells infected with HIV-1 after serial passage in the presence of ODNs in the supernatant for up to 3 months, using Foscarnet as positive control, and treated HIV-infected huPBL-SCID mice repeatedly with ODN. Results: Treatment with ODN did not induce mutations of the PPT or the reverse transcriptase polymerase domain in vitro, whereas Foscarnet did. We furthermore demonstrate that ODNs inhibit HIV-1 replication in humanized HIV-infected SCID mice.
Oligohydramnios, Small for Gestational Age and Pregnancy Outcomes: An Analysis Using Precise Measures
Authors: Magann Everett F. , Haas David M. , Hill James B. , Chauhan Suneet P. , Watson Erin M. , Learman Lee A.
Published: November 2011

Background/Aim: Marginal or decreased amniotic fluid volume by ultrasound estimate and fetal growth restriction have been shown to be significantly associated with perinatal mortality. The association of fetal growth restriction and precisely measured amniotic fluid volume is unknown. The purpose of this study was to determine if adverse pregnancy outcomes are more likely in pregnancies complicated by small-for-gestational-age (SGA) neonates and dye-determined oligohydramnios. Methods: Admissions to neonatal intensive care unit (NICU) and other pregnancy outcomes were analyzed in parturients with known amniotic fluid volume, calculated by the dye-dilution technique. The pregnancy outcomes of those with oligohydramnios and SGA were compared with pregnancies complicated by just one of these two conditions and pregnancies with normal fluid and birth weight. Results: Of 202 patients, oligohydramnios was present in 26% (53), SGA in 15% (30) and both conditions in (5%) (11). Logistic regression, controlling for gestational age, demonstrated that the combination of oligohydramnios and SGA, compared to normal growth and fluid strongly predicted NICU admission (OR 11.1; 95% CI 2.1–59.2) but not other complications. (OR 4.8; 95% CI 0.3–62.9). Conclu sions: SGA with oligohydramnios significantly increases the likelihood of a NICU admission, but not other morbidity.
Relationship between Recurrent Miscarriage and Insulin Resistance
Authors: Wang Yunhui , Zhao Huidan , Li Yan , Zhang Jianping , Tan Jianping , Liu Yukun
Published: November 2011

Aims: To investigate the differences in insulin resistance between women with recurrent miscarriage and those with normal pregnancy. Methods: Pregnant women with a history of recurrent miscarriage were included in the patient group (n = 97), while those with no history of abnormal pregnancy were included in the control group (n = 52). Both groups consented to undertake an oral glucose tolerance test and insulin-releasing test between the 5th and 13th weeks of pregnancy. Results: (1) Levels of fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index, and homeostasis model assessment β function were not statistically significantly different (p < 0.05) between the two groups. (2) The area under the curve of glucose and area under the curve of insulin were higher in the patient group than in the control group. The composite insulin sensitivity index of the patient group was lower than that of the control group. The differences in these three parameters between the groups were statistically significant (p < 0.05). Conclusion: Women with a history of recurrent miscarriage are at an increased risk for insulin resistance during the first trimester of a new pregnancy.
Neuromyelitis Optica Immunoglobulin G in Chinese Patients Detected by Immunofluorescence Assay on a Monkey Brain Substrate
Authors: Long Youming , Hu Xueqiang , Peng Fuhua , Lu Zhengqi , Wang Yuge , Yang Yu , Qiu Wei
Published: November 2011

Background: Serum neuromyelitis optica immunoglobulin G (NMO-IgG) is used as a biomarker to differentiate between neuromyelitis optica (NMO) and multiple sclerosis (MS). However, the original assay is expensive and complex and shows low sensitivity. Here, we investigated the potential of NMO-IgG detection using an indirect immunofluorescence (IIF) assay on monkey brains. Methods: NMO-IgG seroprevalence was determined in 168 samples by an IIF assay on a monkey brain substrate. The data were compared with those from a standard mouse brain IIF assay using McNemar and kappa tests. Results: Thirty-one of 50 (62%) NMO patients, 7 of 18 (38.9%) longitudinally extensive transverse myelitis patients, 6 of 57 (10.5%) MS patients, and 5 of 10 (50%) optic neuritis patients were seropositive for NMO-IgG. None of the acute partial transverse myelitis patients (n = 3) or healthy controls (n = 20) was positive. Thus, the sensitivity of the test was 62% for the patients with clinically definite NMO. The specificity was 89.5%, considering the 57 MS patients as the control group. The modified IIF assay on monkey brains and the standard IIF assay based on mouse brains were not significantly different (McNemar test; p = 1.000). The two assays were concordant in 39 seropositive samples and 100 seronegative samples (kappa test; kappa = 0.592, p < 0.0001). Conclusions: Although the modified IIF monkey brain assay was no better than the standard mouse brain IIF assay, we affirmed that NMO-IgG is a sensitive and specific biomarker to differentiate between NMO and MS.
Clinical Usefulness of CEA, CA19-9, and CYFRA 21-1 as Tumor Markers for Urothelial Bladder Carcinoma
Authors: Washino Satoshi , Hirai Masaru , Matsuzaki Atsushi , Kobayashi Yutaka
Published: November 2011

Objective: To evaluate the usefulness of measuring serum CEA, CA19-9, and CYFRA 21-1 levels for the diagnosis and monitoring of bladder cancer. Materials and Methods: Serum levels of CEA, CA19-9, and CYFRA 21-1 were measured in 85 patients with bladder cancer. The absolute level of each marker and the positive rate were compared with the clinical stage and histological grade of the tumor. Changes of the markers were assessed in patients with or without disease progression, and the correlations between survival and positivity/negativity of these markers were also evaluated. Results: A higher serum level of CYFRA 21-1 was significantly correlated with higher tumor stage (p < 0.01) and higher grade (p < 0.05). In contrast, serum CEA and CA19-9 levels did not differ significantly among each stage and grade. The CYFRA 21-1 level increased significantly along with disease progression (from 7.33 ± 13.3 to 55.9 ± 127 ng/ml, p < 0.01). Patients who were positive for CYFRA 21-1 had significantly worse disease-specific survival (p < 0.0001, log rank test). Conclusion: Serum CYFRA 21-1 seems to be a marker of advanced- and high-grade urothelial carcinoma of the bladder. It is useful for monitoring this disease and for predicting the prognosis. In contrast, the clinical usefulness of CEA and CA19-9 as tumor markers was not demonstrated.
Recombination in the Nonstructural Gene Region in Type 2 Dengue Viruses
Authors: Su Ming Wei , Yuan Hanna S. , Chu Woei Chyn
Published: November 2011

In view of the rising prevalence of dengue virus and mixing of host and vector populations, complete full-length sequence determination of dengue strains isolated from different epidemic areas is important for the study of virus evolution, pathogenicity, vaccine efficiency and diagnosis. Based on the genomic analysis of 51 complete dengue virus sequences, all of which cocirculated in Thailand between 1974 and 2001, we report here the occurrence of homologous recombination in the NS5 nonstructural gene region of dengue virus type 2 (DENV-2) strains. In order to analyze those 51 virus sequences at one time, we chose to use a highly sensitive recombination detection program called RDP. When RDP detects a possible recombination event, further bootscanning and phylogenetic tree analyses are applied to these candidate sequences to identify this recombination event. We found that within the DENV-2 subfamily, the strain ThNH63/93 is the evolutionary product of a recombination event between ThNH62/93 and ThD2_0284_90 strains. The strain ThNH62/93 was identified as the major parent, while the strain ThD2_0284_90 was the minor parent. The recombination site was determined to localize between positions 7967 (±36 nt) and 8283 (±36 nt) with a significance level of p < 0.001. Our results showed, for the first time, that an intraserotype recombination event occurred between DENV-2 strains in the nonstructural gene region; by contrast, an interserotype recombination between different serotypes of dengue strains was not identified. This study thus supports the theory that homologous recombination plays a key role in dengue virus evolution.
Urethral Diverticulum with Massive Lithiasis Presenting as a Scrotal Mass
Authors: Labanaris Apostolos P. , Zugor Vahudin , Witt Jorn H. , Nützel Reinhold , Kühn Reinhard
Published: November 2011

Urethral diverticula in men are uncommon clinical entities. Their clinical manifestations include urinary tract infection, hematuria, irritative or obstructive voiding symptoms, ventral bulging and displacement of the penile shaft. Male urethral diverticulum with massive lithiasis presenting as a scrotal mass with stress urinary incontinence as the main symptom is extremely rare. Herein, we present such a case.
Amino Acid Substitution in HCV Core/NS5A Region and Genetic Variation Near IL28B Gene Affect Treatment Efficacy to Interferon plus Ribavirin Combination Therapy
Authors: Akuta Norio , Suzuki Fumitaka , Hirakawa Miharu , Kawamura Yusuke , Sezaki Hitomi , Suzuki Yoshiyuki , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Chayama Kazuaki , Nakamura Yusuke , Kumada Hiromitsu
Published: November 2011

Objective: To evaluate predictive factors of treatment efficacy to interferon (IFN)/ribavirin in patients infected with HCV genotype 1b (HCV-1b). Methods: This study investigated pretreatment predictors, including viral- (aa substitutions in core aa 70/91 and NS5A-ISDR/IRRDR) and host-related factors (genetic variation near IL28B gene), to 48-week IFN/ribavirin in 490 Japanese adults infected with HCV-1b. Results: The proportion of patients who showed end-of-treatment response (ETR), sustained virological response (SVR), and SVR after ETR was 76, 54, and 76%, respectively. There was a significant positive correlation between the number of aa substitutions in ISDR and those in IRRDR. Concerning the substitution of core aa 91, the number of aa substitutions in ISDR/IRRDR of patients with Leu91 was significantly higher than that of patients with Met91. Furthermore, levels of viremia were influenced by aa substitutions in core aa 91 and ISDR/IRRDR. By multivariate analysis, rs8099917 genotype was an important predictor of ETR and SVR. With regard to viral factors, core aa 70/91 was an important predictor of ETR, and SVR after ETR. ISDR was an important predictor of SVR, and SVR after ETR. Conclusion: aa substitution in core/NS5A region and genetic variation near IL28B were important predictors of treatment efficacy to IFN/ribavirin.
Accuracy of Different Equations for Estimating Fetal Weight
Authors: Benavides-Serralde Andrés , Hernandez-Andrade Edgar , Fernandez-Lara Alfredo , Figueras Francesc , Moreno-Álvarez Oscar , Camargo-Marín Lisbeth , Acevedo-Gallegos Sandra , Gallardo-Gaona Juan , Velázquez-Torres Berenice , Guzmán-Huerta Mario
Published: November 2011

Objective: To evaluate the accuracy of ten equations based on ultrasound parameters for estimating fetal weight (FW). Study Design: A cross-sectional study was performed in 250 healthy women with normal singleton pregnancies between 34 and 41 weeks of gestation. FW estimations calculated according to ten different equations were compared against birth weight (BW) which was determined within 72 h after FW estimation. Estimated error rate, intraclass correlation coefficient, and agreement between BW and FW calculated by each formula were analyzed. Results: Most of the formulas were inaccurate in predicting BW, only 2 formulas showed less than 10% of the measurements lying within the 10% of estimated error. Four formulas tended to overestimate, while six tended to underestimate FW. Conclusions: Appropriate equations for estimating FW in all populations should be developed. However, where there are no local growth curves, the accuracy of the available fetal growth equations should be tested.
First-Trimester Screening for Trisomy 21 with Adjustment for Biochemical Results of Previous Pregnancies
Authors: Wright David , Syngelaki Argyro , Birdir Cahit , Bedei Ivonne , Nicolaides Kypros H.
Published: November 2011

Objective: To investigate the effect of associations in serum free β-hCG and PAPP-A between successive pregnancies on the performance of screening for trisomy 21 at 11–13 weeks’ gestation. Methods: In 8,499 women with two consecutive pregnancies, including 49 women with fetal trisomy 21 in the second pregnancy, the correlation in serum free β-hCG multiples of the median (MoM) and PAPP-A MoM between pregnancies was determined, and the effects of correcting for the correlation on the performance of screening was estimated. Results: There were significant associations between pregnancies in free β-hCG MoM (r = 0.4435) and PAPP-A MoM (r = 0.4796). In screening by maternal age and biochemistry at a risk cutoff of 1 in 100, in the second pregnancies the false-positive rate was 35.5% for those with screen-positive results in the first pregnancy, and this was reduced to 17.1% after adjustment for the results of the first pregnancy. Similarly, in women with screen-negative results in the first pregnancy, adjustment for the results improved the detection rate in the second pregnancy from 66.7 to 81.2%. Conclusions: In screening for trisomy 21, adjustment for the biochemical findings in a previous pregnancy has major effects on individual patient-specific risks, increases the detection rate and reduces the false-positive rate.
The Extended Reconstruction of the Pubocervical Layer Appears Superior to the Simple Plication of the Bladder Adventitia concerning Anterior Colporrhaphy: A Description of Two Techniques in an Observational Retrospective Analysis
Authors: Link Gerold , van Dooren Ivo M.A. , Wieringa Nienke M.
Published: November 2011

Aims: This observational retrospective analysis was done to compare the plication of the bladder adventitia with the reconstruction of the pubocervical layer concerning the reoperation rate for recurrent cystocele. Methods: Sixty-five patients underwent an anterior vaginal wall repair using traditional techniques. In 11 patients, the prolapse was corrected by simply plicating the adventitia of the posterior bladder wall (group A), and in 54 patients the pubocervical layer was rebuilt using structures of the endopelvic fascia following far lateral dissection of the vaginal flaps (group B). The anatomical state was documented via the Pelvic Organ Prolapse Quantification system. Results: The overall reoperation rate of cystoceles was 6% after a mean follow-up of 2 years. Three out of 11 patients of group A and 1/54 patients of group B underwent repeat surgery (p < 0.005). No complications were observed in group A (0/11). In contrast, seven complications were related to the reconstruction of the pubocervical layer (7/54, p > 0.05). Two patients presented with ureteral obstruction, one of them requiring temporary nephrostomy. Conclusion: Compared with the plication of the bladder adventitia, the reoperation rate after reconstruction of the pubocervical layer is diminished. However, because of potential risks of ureteral injury, the procedure demands serious precaution.
Analysis of an Unusual Cluster of Systemic Reactions to Subcutaneous Specific Immunotherapy with Respiratory Allergens in One Allergy Center
Authors: Scherer Kathrin , Schindler Christian , Arnold Andreas , Bach Silvy , Bircher Andreas J.
Published: November 2011

Systemic reactions to subcutaneous immunotherapy occur despite all necessary precautions and experienced staff and should prompt a search for causative factors. We present an analysis of 11 reactions, 8 of them within a short period. The patients and reactions were evaluated regarding extract errors (composition, concentration), dosing errors, ignored contraindications to specific subcutaneous immunotherapy, introductions versus maintenance phase and accidental intravascular injection. No single or common cause could be identified. Statistical analysis suggests that exceptional clusters of systemic reactions such as these may be just random cumulations without identifiable cause.
The Angiogenic Switch for Vascular Endothelial Growth Factor-A and Cyclooxygenase-2 in Prostate Carcinoma: Correlation with Microvessel Density, Androgen Receptor Content and Gleason Grade
Authors: Gyftopoulos K. , Vourda K. , Sakellaropoulos G. , Perimenis P. , Athanasopoulos A. , Papadaki E.
Published: November 2011

Objective: Angiogenesis is essential for tumor growth and metastasis; however, angiogenic factors are not uniformly expressed in prostate carcinoma. Our aim was to determine the expression of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) in prostate carcinomas in relation to intratumoral microvessel density (MVD), tumor grade and androgen receptor (AR) status. Materials and Methods: The expression of AR, VEGF-A and COX-2 was immunohistochemically evaluated in 24 benign prostatic hyperplasia (BPH) and 139 prostate carcinoma cases. MVD was evaluated by CD34 immunostaining. Results: Nuclear AR expression was inversely related to tumor grade (p < 0.001). MVD was strongly related to tumor grade, VEGF-A and COX-2 (p < 0.001 in all comparisons). VEGF-A expression increased with tumor grade (p < 0.01) and was inversely related to stromal AR expression. COX-2 was present in both BPH and prostate carcinoma, but its expression increased with tumor grade (p < 0.01). High-grade neoplasms presented low-to-moderate VEGF staining intensity compared to strong COX-2 expression. Conclusions: Both VEGF-A and COX-2 expression is positively correlated with tumor grade and MVD. However, in Gleason 8–10 tumors, VEGF expression is moderate while COX-2 immunostaining is intense, suggesting a possible switch in the role of these two angiogenic factors in poorly differentiated neoplasms.
Phenotypic Variability in Fetuses with Down Syndrome: A Case-Control Pathological Evaluation
Authors: Ramalho C. , Brandão O. , Matias A. , Montenegro N.
Published: November 2011

Objectives: Evaluation of morphological and morphometric characteristics of fetuses with Down syndrome based on a detailed postmortem examination and comparison of these fetuses with a control group of fetuses with normal karyotype to improve the prenatal knowledge of Down syndrome characteristics. Material and Methods: A case-control study was undertaken in a tertiary referral hospital. The Down syndrome fetuses (50) were compared with chromosomally normal fetuses (47) matched for gestational age. Biometric and morphological parameters were compared. Results: The biometry of fetuses with Down syndrome differs from control fetuses only in the occipitofrontal diameter and in the nasal bone length. There were craniofacial anomalies in 96% of fetuses with Down syndrome and in 51% of fetuses with normal karyotype. With the exception of small ears, all craniofacial features analyzed were significantly different between Down syndrome fetuses and control fetuses. All extremity features of fetuses with Down syndrome were significantly different from fetuses without Down syndrome. There were 31 fetuses with Down syndrome (62%) with 55 internal anomalies. Nineteen fetuses (38.8%) showed 27 cardiac anomalies. Six fetuses had more than one anomaly. There were 18 fetuses (36%) with 28 noncardiac anomalies. Discussion: The importance of studying the morphological characteristics of fetuses with Down syndrome is the contribution to a better knowledge of fetal characteristics and probably to optimize prenatal diagnosis.
Serous Adenocarcinoma of the Uterine Cervix: A Clinicopathological Study of 12 Cases and a Review of the Literature
Authors: Togami Shinichi , Kasamatsu Takahiro , Sasajima Yuko , Onda Takashi , Ishikawa Mitsuya , Ikeda Shun-ichi , Kato Tomoyasu , Tsuda Hitoshi
Published: November 2011

Background/Aims: To determine the clinicopathological characteristics and potentially associated outcomes in patients diagnosed with serous adenocarcinoma of the uterine cervix. Methods: The records of surgically-treated patients with pathological stage pT1b–2b serous adenocarcinoma were reviewed. Results: Of 12 patients with serous adenocarcinoma who underwent radical hysterectomy, five had pT1b1N0 disease, two pT1b1N1, two pT1b2N0, and three pT2bN1. The 5-year overall survival rate for patients with or without parametrial involvement (pT2b vs. pT1b) was 0 and 89%, respectively. The 3-year recurrence-free survival rate for those with or without parametrial involvement was 33 and 89%, respectively. Four patients suffered recurrence, namely one of those who had pT1b (1/9, 11%) and 3 of those who had pT2b disease (100%). The sites of recurrence of pT2b disease were outside the pelvis in all 3 patients. Of these, 2 (67%) had peritoneal spread and 1 distant node metastasis. Conclusion: While patients with pathological stage pT1b disease may have a relatively favorable outcome after radical surgery, those with more advanced disease have a poor prognosis because of extra-pelvic recurrence.
Risk for Advanced-Stage Endometrial Cancer in Surgical Specimens from Patients with Complex Endometrial Hyperplasia with Atypia
Authors: Eddib Abeer , Allaf Baraa , Lee Jenny , Yeh John
Published: November 2011

Objectives: To determine the incidence of endometrial cancer in patients undergoing hysterectomy for atypical complex endometrial hyperplasia and to study the risk of advanced endometrial cancer that may be associated with extra-uterine disease. Methods: A retrospective chart review was performed of the records of all women who underwent hysterectomy for a preoperative diagnosis of complex hyperplasia with atypia from two teaching hospitals between 1999 and 2006. Demographic and clinical variables were collected and analyzed for the 80 patients identified by the initial screening methods. Results: After screening and exclusions, 66 women with a preoperative diagnosis of atypical complex hyperplasia who subsequently underwent a hysterectomy were identified. Eleven of the 66 patients with atypical complex hyperplasia had a diagnosis of endometrial carcinoma in the hysterectomy specimens (17%). No endometrial cancer patient was staged greater than stage 1B or had greater than grade 2 disease. The patients with endometrial cancer were older (p < 0.05). Evidence of myometrial invasion was found in 63% (7/11) of the cancer cases, but all were less than 50% of the myometrium. Conclusion: Endometrial cancer found at the time of hysterectomy for complex hyperplasia with atypia may be associated with less advanced disease.
Body Mass Index and Severe Postpartum Hemorrhage
Authors: Paglia Michael J. , Grotegut Chad A. , Johnson Lauren N.C. , Thames Betty , James Andra H.
Published: November 2011

Background/Aims: The purpose of this study was to determine the relationship between maternal characteristics and severe postpartum hemorrhage (PPH). Methods: Medical records of women who delivered at Duke University Hospital between 2001 and 2004 with an ICD-9 code for PPH were reviewed. Women with PPH who received blood component therapy (severe PPH) were selected as cases and compared with controls matched for age, parity and mode of delivery. Results: Among 12,476 deliveries, there were 109 women with severe PPH. Hispanic women had an almost fourfold increase in the odds of severe PPH [OR 3.9 (1.8, 8.7)] that persisted when controlling for other significant predictors of PPH. Women with PPH were almost two times more likely [OR 1.8 (1.1, 3.1)] to have a BMI <30 when controlling for Hispanic ethnicity, oxytocin exposure, labor induction, treatment with magnesium and chorioamnionitis. Conclusion: Systemic factors as well as obstetrical factors modify the risk of severe PPH. Hispanic women and women with a BMI <30 are more likely to have severe PPH. When mode of delivery is controlled for, BMI ≧30 is associated with a reduced risk of severe PPH.