bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of CT and CT arthrography in diagnosing equine stifle injury in a Rheinlander gelding
Authors: CRIJNS C. P. , GIELEN I. M. V. L. , Van BREE H. J. J. , BERGMAN E. H. J. 
Published: April 2010

SummaryA 5‐year‐old Rheinlander gelding was evaluated for left hindlimb stifle lameness. The lameness was localised to the stifle, but source of the lameness was not specifically diagnosed from the physical, radiographic and ultrasonographic examinations. Computed tomography (CT) and CT arthrography were therefore used for further investigation since these imaging techniques image bony structures, cartilage and soft tissues. This examination showed multiple lesions in the stifle: an osteochondrosis dissecans like lesion of the medial femoral condyle, bony fragments, cartilage trauma and caudal cruciate ligament injury. The prognosis for continuing use as a sports horse was regarded as unfavourable. Therefore, the horse was subjected to euthanasia. All CT findings were confirmed by gross pathology.The CT and CT arthrography examination in this case provided a diagnosis not achieved with other conventional imaging techniques.
Epidemiologic Study of Human Influenza Virus Infection in South Korea from 1999 to 2007: Origin and Evolution of A/Fujian/411/2002-Like Strains
Authors: Kang Seokha , Yang In Seok , Lee Joo-Yeon , Park Yiho , Oh Hee-Bok , Kang Chun , Kim Kyung Hyun 
Published: April 2010

ABSTRACT
Influenza epidemics arise through the accumulation of viral genetic changes, culminating in a novel antigenic type that is able to escape host immunity. Following an outbreak of the A/Fujian/411/2002-like strains in Asia, including China, Japan, and South Korea, in 2002, Australia and New Zealand experienced substantial outbreaks of the same strains in 2003, and subsequently worldwide outbreaks occurred in the 2003-2004 season. The emergence of A/Fujian/411/2002-like strains coincided with a higher level of influenza-like illness in South Korea than what is seen at the peak of a normal season, and there was at least a year's difference between South Korea and the United States. Genetic evolution of human influenza A/H3N2 viruses was monitored by sequence analysis of hemagglutinin (HA) genes collected in Asia, including 269 (164 new) HA genes isolated in South Korea from 1999 to 2007. The Fujian-like influenza strains were disseminated with rapid sequence variation across the antigenic sites of the HA1 domain, which sharply distinguished between the A/Moscow/10/1999-like and A/Fujian/411/2002-like strains. This fast variation, equivalent to approximately 10 amino acid changes within a year, occurred in Asia and would be the main cause of the disappearance of the reassortants, although the reassortant and nonreassortant Fujian-like strains circulated simultaneously in Asia.
Rapid Diagnosis of Old World Leishmaniasis by High-Resolution Melting Analysis of the 7SL RNA Gene
Authors: Nasereddin Abedelmajeed , Jaffe Charles L. 
Published: April 2010

ABSTRACT

High-resolution melt analysis PCR (HRM PCR) for diagnosis of Old World
Leishmania
was developed using the 7SL RNA gene. Cutaneous leishmaniasis samples were analyzed. Sensitivity and specificity of HRM PCR were significantly better (
P
< 0.001) than those of internal transcribed spacer 1 PCR and similar to those of kinetoplast DNA PCR.
Diagnostic Value of PCR Analysis of Bacteria and Fungi from Blood in Empiric-Therapy-Resistant Febrile Neutropenia
Authors: Nakamura Akiko , Sugimoto Yuka , Ohishi Kohshi , Sugawara Yumiko , Fujieda Atsushi , Monma Fumihiko , Suzuki Kei , Masuya Masahiro , Nakase Kazunori , Matsushima Yoshiko , Wada Hideo , Katayama Naoyuki , Nobori Tsutomu 
Published: April 2010

ABSTRACTThis study aimed to assess the clinical utility of PCR for the analysis of bacteria and fungi from blood for the management of febrile neutropenic patients with hematologic malignancies. Using a PCR system able to detect a broad range of bacteria and fungi, we conducted a prospective pilot study of periodic analyses of blood from patients following intensive chemotherapy. When fever occurred, it was treated with empirical antibiotic therapy, basically without knowledge of the PCR results. In 23 febrile episodes during the neutropenic period, bacteria were detected by PCR in 11 cases, while the same species were identified by blood culture in 3 cases. In 10 out of 11 PCR-positive cases, fever could be managed by empirical therapy. In the empirical-therapy-resistant case, the identification ofStenotrophomonas maltophiliaby PCR led to improvement of fever. No fungi were detected by PCR in febrile cases, whileAspergillus fumigatuswas detected in one afebrile patient, several days before a clinical diagnosis was made. In subsequent sporadic PCR analyses in 15 cases of febrile neutropenia, bacteria were detected by both PCR and blood culture in 7 cases and by PCR alone in 6. Fungi were not detected. While fever was improved by empirical therapy in 12 out of the 13 PCR-positive cases, the identification ofPseudomonas aeruginosaby PCR in one therapy-resistant case contributed to the successful treatment of persistent fever. Our results indicate that PCR analysis of bacteria from blood provides essential information for managing empirical-therapy-resistant febrile neutropenia.
Natural Occurrence of Horizontal Transfer ofMycobacterium avium- Specific Insertion Sequence IS1245toMycobacterium kansasii
Authors: da Silva Rabello Michelle Christiane , de Oliveira Rosangela Siqueira , Silva Rosa Maria , Leao Sylvia Cardoso 
Published: April 2010

ABSTRACTMycobacterium kansasiicarrying IS1245, a highly prevalent insertion sequence amongMycobacterium aviumisolates, was detected in a mixed culture ofM. aviumandM. kansasii. The insertion sequence was stable and able to transpose by a replicative mechanism inM. kansasii. These findings may have significant implications for molecular diagnosis and treatment outcome.
Epidemiology and Genotype Analysis of Emerging Sapovirus-Associated Infections across Europe
Authors: Svraka Sanela , Vennema Harry , van der Veer Bas , Hedlund Kjell-Olof , Thorhagen Margareta , Siebenga Joukje , Duizer Erwin , Koopmans Marion 
Published: April 2010

ABSTRACTSapoviruses (SaVs) belong to theCaliciviridaefamily and can cause gastroenteritis in humans and swine. Despite extensive testing, human sapoviruses have been found only in sporadic cases and in one mixed outbreak in children between 1994 and 2007 in the Netherlands. Here we describe a change in sapovirus epidemiology in the Netherlands resulting in sapovirus outbreaks and infections in adults. From November 2007 to January 2009, 478 outbreaks of acute gastroenteritis were reported to the National Institute for Public Health and the Environment in the Netherlands as a part of ongoing surveillance. Sapoviruses were found to be the most likely cause of 19 outbreaks (4%). During the same 2-year period, sapovirus infections were reported in Sweden, Slovenia, and Hungary. In the Netherlands, further characterization of outbreak strains showed that 12 (63%) sapovirus outbreaks were caused by genotype I.2 viruses. Most patients were adults older than 60 years (range, 1 to 100 years). Phylogenetic analysis using all presently available SaV sequences showed high homology between genotype I.2 strains detected in different geographical regions (Sweden, Slovenia, Taiwan, Japan, and Russia) since 2007. These first reported outbreaks of sapovirus infections in adults in the Netherlands were remarkable. Detection of identical genotypes in many samples might suggest that these viruses have the same origin, and since the infection is spreading fast, the prevalence of sapovirus infection may be increasing. The incidence of sapovirus infections in these countries suggests that a substantial part of Europe is affected by this virus.
Host Factors Associated with the Sindbis Virus RNA-Dependent RNA Polymerase: Role for G3BP1 and G3BP2 in Virus Replication
Authors: Cristea Ileana M. , Rozjabek Heather , Molloy Kelly R. , Karki Sophiya , White Laura L. , Rice Charles M. , Rout Michael P. , Chait Brian T. , MacDonald Margaret R. 
Published: April 2010

ABSTRACT

Sindbis virus (SINV) is the prototype member of the
Alphavirus
genus, whose members cause severe human diseases for which there is no specific treatment. To ascertain host factors important in the replication of the SINV RNA genome, we generated a SINV expressing nsP4, the viral RNA-dependent RNA polymerase, with an in-frame 3×Flag epitope tag. Proteomic analysis of nsP4-containing complexes isolated from cells infected with the tagged virus revealed 29 associated host proteins. Of these, 10 proteins were associated only at a later time of infection (12 h), 14 were associated both early and late, and five were isolated only at the earlier time (6 h postinfection). These results demonstrate the dynamic nature of the virus-host interaction that occurs over the course of infection and suggest that different host proteins may be required for the multiple functions carried out by nsP4. Two related proteins found in association with nsP4 at both times of infection, GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) and G3BP2 were also previously identified as associated with SINV nsP2 and nsP3. We demonstrate a likely overlapping role for these host factors in limiting SINV replication events. The present study also identifies 10 host factors associated with nsP4 6 h after infection that were not found to be associated with nsP2 or nsP3. These factors are candidates for playing important roles in the RNA replication process. Identifying host factors essential for replication should lead to new strategies to interrupt alphavirus replication.
Attenuation of age- and sucrose-induced insulin resistance and syndrome X by a synergistic antioxidant cocktail: the AMIS syndrome and HISS hypothesisThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Lautt W. Wayne , Ming Zhi , Legare Dallas J. 
Published: April 2010

Absence of meal-induced insulin sensitization (AMIS) results in a predictable progression of dysfunctions, including postprandial hyperglycemia, compensatory hyperinsulinemia, resultant hyperlipidemia, increased oxidative stress, and obesity, progressing to syndrome X and diabetes. To one year of age, rats show a slow development of AMIS, but this can be potentiated by addition of a low-dose sucrose supplement to the diet. Provision of a synergistic antioxidant cocktail consisting of S-adenosylmethionine, vitamin E, and vitamin C (Samec) attenuates the rate and extent of development of AMIS in both normal aging animals and in aging animals on the sucrose diet. Adiposity, assessed from weighed regional fat masses and from bioelectrical impedance to estimate whole-body adiposity, correlated strongly with AMIS (r2 = 0.7–0.8). Rats given the sucrose supplement had accelerated AMIS and developed fasting hyperinsulinemia and postprandial hyperglycemia, hyperlipidemia, hyperinsulinemia, and adiposity. Samec completely compensated for the negative impact of this sucrose supplement and attenuated development of the associated dysfunctions. AMIS is explained by the HISS (hepatic insulin-sensitizing substance) hypothesis, which is outlined in the paper.
Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophagesThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Sarna Lindsei K. , Wu Nan , Hwang Sun-Young , Siow Yaw L. , O Karmin 
Published: April 2010

Oxidative stress and amplified redox signaling contribute to the pathogenesis of many human diseases including atherosclerosis. The superoxide-generating phagocytic NADPH oxidase is a key source of oxidative stress in the developing atheroma. The aim of the present study was to examine the effect of berberine, a plant-derived alkaloid, on NADPH oxidase-mediated superoxide anion production in macrophages. Lipopolysaccharide (LPS) treatment activated NADPH oxidase in THP-1 monocyte-derived macrophages and increased the intracellular level of superoxide anions. Preincubation of cells with berberine demonstrated a concentration-dependent (10–50 µmol/L) and time-dependent (6–24 h) inhibition of superoxide anion generation in LPS-stimulated macrophages. Cell viability tests confirmed that berberine, at concentrations sufficient for inhibiting NADPH oxidase-mediated superoxide anion generation in macrophages, did not affect cell viability. Real-time PCR analysis revealed that addition of berberine to the culture medium was able to reduce gp91phoxmRNA expression in LPS-treated cells. Berberine also restored superoxide dismutase (SOD) activity, which was found to be inhibited by LPS treatment. In conclusion, results from the present study demonstrate that berberine can effectively reduce intracellular superoxide levels in LPS- stimulated macrophages. Such a restoration of cellular redox by berberine is mediated by its selective inhibition of gp91phoxexpression and enhancement of SOD activity. The therapeutic relevance of berberine in the prevention and management of atherosclerosis remains to be further investigated.
Proteomic Characterization of Novel Alternative Splice Variant Proteins in Human Epidermal Growth Factor Receptor 2/neu–Induced Breast Cancers
Authors: Menon Rajasree , Omenn Gilbert S. 
Published: April 2010

Abstract
Multifaceted alternative splicing in cancer cells greatly diversifies protein structure independently of genome changes, but the characterization of cancer-associated splice variants is quite limited. In this study, we used mass spectrometric data to interrogate a custom-built database created with three-frame translations of mRNA sequences from Ensembl and ECgene to find alternative splice variant proteins. In mass spectrometric files from liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses of normal mouse mammary glands or mammary tumors derived from conditional human epidermal growth factor receptor 2 (Her2)/neu transgenic mice, we identified a total of 608 alternative splice variants, of which peptides from 216 proteins were found only in the tumor sample. Among the 608 splice variants were 68 novel proteins that were not completely matched to any known protein sequence in mice, for which we found known functional motifs. Biological process enrichment analysis of the splice variants identified suggested the involvement of these proteins especially in cell motility and translation initiation. The cancer-associated differentially expressed splice variant proteins offer novel biomarker candidates that may function in breast cancer progression or metastasis. Cancer Res; 70(9); 3440–9. ©2010 AACR.
Id2 Promotes Tumor Cell Migration and Invasion through Transcriptional Repression of Semaphorin 3F
Authors: Coma Silvia , Amin Dhara N. , Shimizu Akio , Lasorella Anna , Iavarone Antonio , Klagsbrun Michael 
Published: April 2010

Abstract
Id proteins (Id1 to Id4) are helix-loop-helix transcription factors that promote metastasis. It was found that Semaphorin 3F (SEMA3F), a potent inhibitor of metastasis, was repressed by Id2. High metastatic human tumor cell lines had relatively high amounts of Id2 and low SEMA3F levels compared with their low metastatic counterparts. No correlation between metastatic potential and expression of the other Id family members was observed. Furthermore, ectopic expression of Id2 in low metastatic tumor cells downregulated SEMA3F and, as a consequence, enhanced their ability to migrate and invade, two requisite steps of metastasis in vivo. Id2 overexpression was driven by the c-myc oncoprotein. SEMA3F was a direct target gene of the E47/Id2 pathway. Two E-box sites, which bind E protein transcription factors including E47, were identified in the promoter region of the SEMA3F gene. E47 directly activated SEMA3F promoter activity and expression and promoted SEMA3F biological activities, including filamentous actin depolymerization, inactivation of RhoA, and inhibition of cell migration. Silencing of SEMA3F inhibited the E47-induced SEMA3F expression and biological activities, confirming that these E47-induced effects were SEMA3F dependent. E47 did not induce expression of the other members of the SEMA3 family. Id2, a dominant-negative inhibitor of E proteins, abrogated the E47-induced SEMA3F expression and biological activities. Thus, high metastatic tumor cells overexpress c-myc, leading to upregulation of Id2 expression; the aberrantly elevated amount of Id2 represses SEMA3F expression and, as a consequence, enhances the ability of tumor cells to migrate and invade. Cancer Res; 70(9); 3823–32. ©2010 AACR.
Prospective Study of the Association of Serum γ-Glutamyltransferase with Cervical Intraepithelial Neoplasia III and Invasive Cervical Cancer
Authors: Strasak Alexander M. , Goebel Georg , Concin Hans , Pfeiffer Ruth M. , Brant Larry J. , Nagel Gabriele , Oberaigner Willi , Concin Nicole , Diem Günter , Ruttmann Elfriede , Gruber-Moesenbacher Ulrike , Offner Felix , Pompella Alfonso , Pfeiffer Karl P. , Ulmer Hanno ,   the VHM&PP Study Group
Published: April 2010

Abstract
Epidemiologic studies indicate that elevated levels of γ-glutamyltransferase (GGT), a key enzyme of glutathione metabolism, might be associated with increased cancer risk. Furthermore, preclinical studies support a role for GGT in tumor invasion and progression. However, the relationship between GGT and risks of cervical intraepithelial neoplasia III (CIN-III) and invasive cervical cancer (ICC) have not been evaluated. We investigated the association of enzymatically determined GGT in blood serum with subsequent incidence of CIN-III and ICC in a prospective population-based cohort of 92,843 women ages 18 to 95, of whom 79% had at least one gynecologic examination including Pap smear testing during follow-up. Cox regression was used to compute adjusted hazard ratios (HR) with 95% confidence intervals for the association of GGT with CIN-III and ICC. During median follow-up of 13.8 years, 702 CIN-III and 117 ICC diagnoses were observed. Compared with normal low GGT (&lt;17.99 units/L), risk of ICC was significantly elevated for all other baseline GGT categories, with adjusted HRs of 2.31 (1.49–3.59) for normal high GGT (18.00–35.99 units/L), 2.76 (1.52–5.02) for elevated GGT (36.00–71.99 units/L), and 3.38 (1.63–7.00) for highly elevated GGT [&gt;72.00 units/L; P trend &lt; 0.0001, HR log unit increase 3.45 (1.92–6.19)]. In contrast, associations between GGT serum levels and CIN-III risk were not statistically significant in the main analysis. Exclusion of the first 2 or 5 years of follow-up did not change the results. Effects did not differ by age, body mass index, or socioeconomic status. Our findings implicate GGT in the progression of premalignant cervical lesions to invasive cancer. Cancer Res; 70(9); 3586–93. ©2010 AACR.
Somatic Hypermethylation of MSH2 Is a Frequent Event in Lynch Syndrome Colorectal Cancers
Authors: Nagasaka Takeshi , Rhees Jennifer , Kloor Matthias , Gebert Johannes , Naomoto Yoshio , Boland C. Richard , Goel Ajay 
Published: April 2010

Abstract
Heritable germline epimutations in MSH2 have been reported in a few Lynch syndrome families that lacked germline mutations in the MSH2 gene. It is not known whether somatic MSH2 methylation occurs in MSH2 mutation–positive Lynch syndrome subjects or sporadic colorectal cancers (CRC). Therefore, we determined the methylation status of the MSH2 gene in 268 CRC tissues, including 222 sporadic CRCs and 46 Lynch syndrome tumors that did not express MSH2. We also looked for microsatellite instability (MSI), germline mutations in the MSH2 and EpCAM genes, somatic mutations in BRAF and KRAS, and the CpG island methylator phenotype (CIMP). We observed that somatic MSH2 hypermethylation was present in 24% (11 of 46) of MSH2-deficient (presumed Lynch syndrome) tumors, whereas no evidence for MSH2 methylation existed in sporadic CRCs (MSI and microsatellite stable) or normal colonic tissues. Seven of 11 (63%) patients with MSH2 methylation harbored simultaneous pathogenic germline mutations in the MSH2 gene. Germline EpCAM deletions were present in three of four patients with MSH2 methylation but without pathogenic MSH2 germline mutations. The mean methylation scores at CIMP-related markers were significantly higher in Lynch syndrome tumors with MSH2 methylation than MSH2-unmethylated CRCs. In conclusion, our data provide evidence for frequent MSH2 hypermethylation in Lynch syndrome tumors with MSH2 deficiency. MSH2 methylation in this subset of individuals is somatic and may serve as the “second hit” at the wild-type allele. High levels of aberrant methylation at CIMP-related markers in MSH2-methylated tumors raise the possibility that MSH2 is a target susceptible to aberrant methylation in Lynch syndrome. Cancer Res; 70(8); 3098–108. ©2010 AACR.
CUDC-101, a Multitargeted Inhibitor of Histone Deacetylase, Epidermal Growth Factor Receptor, and Human Epidermal Growth Factor Receptor 2, Exerts Potent Anticancer Activity
Authors: Lai Cheng-Jung , Bao Rudi , Tao Xu , Wang Jing , Atoyan Ruzanna , Qu Hui , Wang Da-Gong , Yin Ling , Samson Maria , Forrester Jeffrey , Zifcak Brian , Xu Guang-Xin , DellaRocca Steven , Zhai Hai-Xiao , Cai Xiong , Munger William E. , Keegan Mitchell , Pepicelli Carmen V. , Qian Changgeng 
Published: April 2010

Abstract
Receptor tyrosine kinase inhibitors have recently become important therapeutics for a variety of cancers. However, due to the heterogeneous and dynamic nature of tumors, the effectiveness of these agents is often hindered by poor response rates and acquired drug resistance. To overcome these limitations, we created a novel small molecule, CUDC-101, which simultaneously inhibits histone deacetylase and the receptor kinases epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in cancer cells. Because of its integrated histone deacetylase inhibition, CUDC-101 synergistically blocked key regulators of EGFR/HER2 signaling pathways, also attenuating multiple compensatory pathways, such as AKT, HER3, and MET, which enable cancer cells to escape the effects of conventional EGFR/HER2 inhibitors. CUDC-101 displayed potent antiproliferative and proapoptotic activities against cultured and implanted tumor cells that are sensitive or resistant to several approved single-targeted drugs. Our results show that CUDC-101 has the potential to dramatically improve the treatment of heterogeneous and drug-resistant tumors that cannot be controlled with single-target agents. Further, they provide a framework to create individual small molecules that simultaneously antagonize multiple biochemically distinct oncogenic targets, suggesting a general paradigm to surpass conventional, single-target cancer therapeutics. Cancer Res; 70(9); 3647–56. ©2010 AACR.