bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trans-packaging of human immunodeficiency virus type 1 genome into Gag virus-like particles in Saccharomyces cerevisiae
Authors: Tomo Naoki , Goto Toshiyuki , Morikawa Yuko 
Published: March 2013

Abstract

Background
Yeast is recognized as a generally safe microorganism and is utilized for the production of pharmaceutical products, including vaccines. We previously showed that expression of human immunodeficiency virus type 1 (HIV-1) Gag protein in Saccharomyces cerevisiae spheroplasts released Gag virus-like particles (VLPs) extracellularly, suggesting that the production system could be used in vaccine development. In this study, we further establish HIV-1 genome packaging into Gag VLPs in a yeast cell system.

Results
The nearly full-length HIV-1 genome containing the entire 5′ long terminal repeat, U3-R-U5, did not transcribe gag mRNA in yeast. Co-expression of HIV-1 Tat, a transcription activator, did not support the transcription. When the HIV-1 promoter U3 was replaced with the promoter for the yeast glyceraldehyde-3-phosphate dehydrogenase gene, gag mRNA transcription was restored, but no Gag protein expression was observed. Co-expression of HIV-1 Rev, a factor that facilitates nuclear export of gag mRNA, did not support the protein synthesis. Progressive deletions of R-U5 and its downstream stem-loop-rich region (SL) to the gag start ATG codon restored Gag protein expression, suggesting that a highly structured noncoding RNA generated from the R-U5-SL region had an inhibitory effect on gag mRNA translation. When a plasmid containing the HIV-1 genome with the R-U5-SL region was coexpressed with an expression plasmid for Gag protein, the HIV-1 genomic RNA was transcribed and incorporated into Gag VLPs formed by Gag protein assembly, indicative of the trans-packaging of HIV-1 genomic RNA into Gag VLPs in a yeast cell system. The concentration of HIV-1 genomic RNA in Gag VLPs released from yeast was approximately 500-fold higher than that in yeast cytoplasm. The deletion of R-U5 to the gag gene resulted in the failure of HIV-1 RNA packaging into Gag VLPs, indicating that the packaging signal of HIV-1 genomic RNA present in the R-U5 to gag region functions similarly in yeast cells.

Conclusions
Our data indicate that selective trans-packaging of HIV-1 genomic RNA into Gag VLPs occurs in a yeast cell system, analogous to a mammalian cell system, suggesting that yeast may provide an alternative packaging system for lentiviral RNA.
C-reactive protein/oxidised low-density lipoprotein/β2-glycoprotein I complex promotes atherosclerosis in diabetic BALB/c mice via p38mitogen-activated protein kinase signal pathway
Authors: Zhang Rui , Zhou Sai-Jun , Li Chun-Jun , Wang Xiao-Nan , Tang Yun-Zhao , Chen Rui , Lv Lin , Zhao Qian , Xing Qiu-Ling , Yu De-Min , Yu Pei 
Published: March 2013

Abstract

Background
The aim of this study was to investigate the effect of C-reactive protein/oxidised low-density lipoprotein/β2-glycoprotein I (CRP/oxLDL/β2GPI) complex on atherosclerosis (AS) in diabetic BALB/c mice.

Methods
BALB/c mice were fed high-fat and normal diet. Eight weeks later, the mice fed with high-fat diet were injected with streptozotocin (STZ) to induce diabetes. The diabetic mice were respectively injected twice monthly with 20 μg oxLDL, 20 μg β2GPI, 40 μg oxLDL/β2GPI complex, 44 μg CRP/oxLDL/β2GPI complex, and PBS. Aortas were stained with Sudan IV to investigate lipid plaque formation. The infiltration condition of smooth muscle cells (SMCs), macrophages, and T cells in the aortas were determined by immunohistochemistry (IH). The mRNA expressions of receptors associated with lipid metabolism were quantified by real-time PCR. The phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and MKK3/6 in aorta tissues were assessed by Western blot. The expression of inflammation cytokines was evaluated by protein chip.

Results
The lipid plaques were more extensive, the lumen area was obviously narrower, the ratio of intima and media thickness were increased, and the normal internal elastic lamia structure and endothelial cell disappeared (P < 0.05) in the oxLDL and CRP/oxLDL/β2GPI groups (P < 0.05). CRP/oxLDL/β2GPI complex dramatically promoted infiltration of SMCs, macrophages, and T cells, improved the mRNA expression of ABCA1 and ABCG1, but reduced the mRNA expression of SR-BI and CD36 and increased the phosphorylation of p38MAPK and MKK3/6 (all P < 0.05). The highest expression levels of IL-1, IL-9, PF-4, bFGF, and IGF-II were detected in the CRP/oxLDL/β2GPI group (P < 0.05).

Conclusions
CRP/oxLDL/β2GPI complex aggravated AS in diabetic BALB/c mice by increasing lipid uptake, the mechanism of which may be mediated by the p38MAPK signal pathway.
Anal phyllodes tumor in a male patient: a unique case presentation and literature review
Authors: Ho Szu-pei , Tseng Hui-hwa , King TM , Chow Philip-C 
Published: March 2013

AbstractAbstractLesions of anogenital mammary-like glands are rare, and only 44 female cases have been reported. Herein, we describe a particularly rare case of phyllodes tumor of anogenital mammary-like glands in a 41-year-old male presenting anal bleeding. Papillectomy was performed. The excised tumor was circumscribed in shape, and after it was sliced into sections, it was noted that there were leaf-like slits on the surface of cut side. Under the microscope, the tumor was found to be biphasic, with a bland glandular epithelium and low-to-intermediate cellular stroma, which together created the leaf-like slits. Gynecomastoid hyperplasia was evident at the periphery. The epithelium showed immuno-activity for ER, PR(focal), AR, and GCDFP-15. The stromal cells showed positive staining for CD34 and vimentin. The morphology and immunophenotype were similar to benign phyllodes tumors of breast. To the best of our knowledge, this case report represents the first case of phyllodes tumor of anogenital mammary-like glands with gynecomastoid hyperplasia at the periphery in a male patient. To make a diagnosis, we had to differentiate this lesion from hidradenoma papilliferum of skin appendage, phyllodes tumor of ectopic prostatic tissue, and other tumors of anogenital mammary-like glands analogous to the breast tumor (e.g., fibroadenoma phyllodes, periductal stromal sarcoma, and spindle cell carcinoma). While gynecomastia of male breast is usually a result of hormone imbalance, our patient’s tumor did not seem to be related to peripheral hormone status in the anogenital mammary-like glands. Nevertheless, because hormone imbalance has been strongly related to male breast cancer, hormone levels may need to be followed in male patients who have this rare malady.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1509145815899177
Magnetic resonance imaging and genetic investigation of a case of rottweiler leukoencephalomyelopathy
Authors: Hirschvogel Katrin , Matiasek Kaspar , Flatz Katharina , Drögemüller Michaela , Drögemüller Cord , Reiner Bärbel , Fischer Andrea 
Published: March 2013

Abstract

Background
Leukoencephalomyelopathy is an inherited neurodegenerative disorder that affects the white matter of the spinal cord and brain and is known to occur in the Rottweiler breed. Due to the lack of a genetic test for this disorder, post mortem neuropathological examinations are required to confirm the diagnosis. Leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate levels is a rare, autosomal recessive disorder in humans that was recently described to have clinical features and magnetic resonance imaging (MRI) findings that are similar to the histopathologic lesions that define leukoencephalomyelopathy in Rottweilers. Leukoencephalopathy with brain stem and spinal cord involvement is caused by mutations in the DARS2 gene, which encodes a mitochondrial aspartyl-tRNA synthetase. The objective of this case report is to present the results of MRI and candidate gene analysis of a case of Rottweiler leukoencephalomyelopathy to investigate the hypothesis that leukoencephalomyelopathy in Rottweilers could serve as an animal model of human leukoencephalopathy with brain stem and spinal cord involvement.

Case presentation
A two-and-a-half-year-old male purebred Rottweiler was evaluated for generalised progressive ataxia with hypermetria that was most evident in the thoracic limbs. MRI (T2-weighted) demonstrated well-circumscribed hyperintense signals within both lateral funiculi that extended from the level of the first to the sixth cervical vertebral body. A neurodegenerative disorder was suspected based on the progressive clinical course and MRI findings, and Rottweiler leukoencephalomyelopathy was subsequently confirmed via histopathology. The DARS2 gene was investigated as a causative candidate, but a sequence analysis failed to identify any disease-associated variants in the DNA sequence.

Conclusion
It was concluded that MRI may aid in the pre-mortem diagnosis of suspected cases of leukoencephalomyelopathy. Genes other than DARS2 may be involved in Rottweiler leukoencephalomyelopathy and may also be relevant in human leukoencephalopathy with brain stem and spinal cord involvement.
Blood transfusion in cardiac surgery is a risk factor for increased hospital length of stay in adult patients
Authors: Galas Filomena RBG , Almeida Juliano P , Fukushima Julia T , Osawa Eduardo A , Nakamura Rosana E , Silva Carolina MPDC , de Almeida Elisângela Pinto Marinho , Auler Jose Otavio Costa , Vincent Jean-Louis , Hajjar Ludhmila A 
Published: March 2013

Abstract

Background
Allogeneic red blood cell (RBC) transfusion has been proposed as a negative indicator of quality in cardiac surgery. Hospital length of stay (LOS) may be a surrogate of poor outcome in transfused patients.

Methods
Data from 502 patients included in Transfusion Requirements After Cardiac Surgery (TRACS) study were analyzed to assess the relationship between RBC transfusion and hospital LOS in patients undergoing cardiac surgery and enrolled in the TRACS study.

Results
According to the status of RBC transfusion, patients were categorized into the following three groups: 1) 199 patients (40%) who did not receive RBC, 2) 241 patients (48%) who received 3 RBC units or fewer (low transfusion requirement group), and 3) 62 patients (12%) who received more than 3 RBC units (high transfusion requirement group). In a multivariable Cox proportional hazards model, the following factors were predictive of a prolonged hospital length of stay: age higher than 65 years, EuroSCORE, valvular surgery, combined procedure, LVEF lower than 40% and RBC transfusion of > 3 units.

Conclusion
RBC transfusion is an independent risk factor for increased LOS in patients undergoing cardiac surgery. This finding highlights the adequacy of a restrictive transfusion therapy in patients undergoing cardiac surgery.

Trial registration
Clinicaltrials.gov identifier: NCT01021631.
The hCMEC/D3 cell line as a model of the human blood brain barrier
Authors: Weksler Babette , Romero Ignacio A , Couraud Pierre-Olivier 
Published: March 2013

Abstract
Since the first attempts in the 1970s to isolate cerebral microvessel endothelial cells (CECs) in order to model the blood–brain barrier (BBB) in vitro, the need for a human BBB model that closely mimics the in vivo phenotype and is reproducible and easy to grow, has been widely recognized by cerebrovascular researchers in both academia and industry. While primary human CECs would ideally be the model of choice, the paucity of available fresh human cerebral tissue makes wide-scale studies impractical. The brain microvascular endothelial cell line hCMEC/D3 represents one such model of the human BBB that can be easily grown and is amenable to cellular and molecular studies on pathological and drug transport mechanisms with relevance to the central nervous system (CNS). Indeed, since the development of this cell line in 2005 over 100 studies on different aspects of cerebral endothelial biology and pharmacology have been published. Here we review the suitability of this cell line as a human BBB model for pathogenic and drug transport studies and we critically consider its advantages and limitations.
Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care
Authors: Llewelyn Martin J , Berger Mario , Gregory Mark , Ramaiah Ravi , Taylor Amanda L , Curdt Ingo , Lajaunias Frédéric , Graf Rolf , Blincko Stuart J , Drage Stephen , Cohen Jonathan 
Published: March 2013

Abstract
Introduction
Although many sepsis biomarkers have shown promise in selected patient groups, only C-reactive protein and procalcitonin (PCT) have entered clinical practice. The aim of this study was to evaluate three promising novel sepsis biomarkers in unselected patients at admission to intensive care. We assessed the performance of pancreatic stone protein (PSP), soluble CD25 (sCD25) and heparin binding protein (HBP) in distinguishing patients with sepsis from those with a non-infective systemic inflammatory response and the ability of these markers to indicate severity of illness.

Methods
Plasma levels of the biomarkers, PCT and selected inflammatory cytokines were measured in samples taken from 219 patients during the first six hours of admission to intensive or high dependency care. Patients with a systemic inflammatory response were categorized as having sepsis or a non-infective aetiology, with or without markers of severity, using standard diagnostic criteria.

Results
Both PSP and sCD25 performed well as biomarkers of sepsis irrespective of severity of illness. For both markers the area under the receiver operating curve (AUC) was greater than 0.9; PSP 0.927 (0.887 to 0.968) and sCD25 0.902 (0.854 to 0.949). Procalcitonin and IL6 also performed well as markers of sepsis whilst in this intensive care unit (ICU) population, HBP did not: PCT 0.840 (0.778 to 0.901), IL6 0.805 (0.739 to 0.870) and HBP 0.607 (0.519 to 0.694). Levels of both PSP and PCT reflected severity of illness and both markers performed well in differentiating patients with severe sepsis from severely ill patients with a non-infective systemic inflammatory response: AUCs 0.955 (0.909 to 1) and 0.837 (0.732 to 0.941) respectively. Although levels of sCD25 did not correlate with severity, the addition of sCD25 to either PCT or PSP in a multivariate model improved the diagnostic accuracy of either marker alone.

Conclusions
PSP and sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the time of admission to intensive or high dependency care. These markers warrant further assessment of their prognostic value. Whereas previously published data indicate HBP has clinical utility in the emergency department, it did not perform well in an intensive-care population.
Cytokine Genetic Variations and Fatigue Among Patients With Breast Cancer
Authors: Bower Julienne E. , Ganz Patricia A. , Irwin Michael R. , Castellon Steven , Arevalo Jesusa , Cole Steven W. 
Published: March 2013

Purpose Fatigue is a common adverse effect of cancer treatment and may persist for years after treatment completion. However, risk factors for post-treatment fatigue have not been determined. On the basis of studies suggesting an inflammatory basis for fatigue, this study tested the hypothesis that expression-regulating polymorphisms in proinflammatory cytokine genes would predict post-treatment fatigue in breast cancer survivors. Patients and Methods Women diagnosed with early-stage breast cancer (n = 171) completed questionnaires to assess fatigue and other behavioral symptoms (ie, depressive symptoms, memory complaints, sleep disturbance) and provided blood for genotyping within 3 months after primary treatment. Genomic DNA was extracted from peripheral-blood leukocytes and assayed for single nucleotide polymorphisms (SNPs) in the promoter regions of three cytokine genes: ILB −511 C>T (rs16944), IL6 −174 G>C (rs1800795), and TNF −308 G>A (rs1800629). An additive genetic risk score was computed by summing the number of high-expression alleles (zero, one, or two) across all three polymorphisms. Results The genetic risk index was significantly associated with fatigue; as the number of high-expression alleles increased, so did self-reported fatigue severity (P = .002). Analyses of individual SNPs showed that TNF −308 and IL6 −174 were independently associated with fatigue (P = .032). The genetic risk index was also associated with depressive symptoms (P = .007) and memory complaints (P = .016). Conclusion These findings further implicate inflammatory processes as contributors to cancer-related fatigue and suggest a new strategy for identifying and treating patients at risk for this symptom based on genetic variants in proinflammatory cytokine genes.
Physician and Stakeholder Perceptions of Conflict of Interest Policies in Oncology
Authors: Lockhart A. Craig , Brose Marcia S. , Kim Edward S. , Johnson David H. , Peppercorn Jeffrey M. , Michels Dina L. , Storm Courtney D. , Schuchter Lynn M. , Rathmell W. Kimryn 
Published: March 2013

Purpose The landscape of managing potential conflicts of interest (COIs) has evolved substantially across many disciplines in recent years, but rarely are the issues more intertwined with financial and ethical implications than in the health care setting. Cancer care is a highly technologic arena, with numerous physician-industry interactions. The American Society of Clinical Oncology (ASCO) recognizes the role of a professional organization to facilitate management of these interactions and the need for periodic review of its COI policy (Policy). Methods To gauge the sentiments of ASCO members and nonphysician stakeholders, two surveys were performed. The first asked ASCO members to estimate opinions of the Policy as it relates to presentation of industry-sponsored research. Respondents were classified as consumers or producers of research material based on demographic responses. A similar survey solicited opinions of nonphysician stakeholders, including patients with cancer, survivors, family members, and advocates. Results The ASCO survey was responded to by 1,967 members (1% of those solicited); 80% were producers, and 20% were consumers. Most respondents (93% of producers; 66% of consumers) reported familiarity with the Policy. Only a small proportion regularly evaluated COIs for presented research. Members favored increased transparency about relationships over restrictions on presentations of research. Stakeholders (n = 264) indicated that disclosure was “very important” to “extremely important” and preferred written disclosure (77%) over other methods. Conclusion COI policies are an important and relevant topic among physicians and patient advocates. Methods to simplify the disclosure process, improve transparency, and facilitate responsiveness are critical for COI management.
Activation of Dioxygen in an Aqueous System of [FeIIITMPyP]–MBTH–O2 to Form Peroxide and Azine from MBTH: Reactivity of Superoxohemin ([FeIIITMPyP–OO]•) and Peroxohemin ([FeIIITMPyP–OO]−)
Authors: Nakano Taku , Kakuda Hiroko , Shinoda Hiroyuki , Moriyama Hiroshi 
Published: March 2013

Abstract
Activation of dioxygen in the heme system is observed in an artificial aqueous model system. It has been demonstrated that in the system of a water-soluble hemin, tetrakis(N-methylpyridyl)porphinatoiron(III) pentachloride ([FeIIITMPyP]Cl5), and a mild reducing reagent, 3-methyl-2-benzothiazolinonehydrazone (MBTH), a superoxide anion radical and hydrogen peroxide have been produced in air at pH 7.0 that degrades hemin. In this complex system with a reductant and an oxidant, we have found the reaction products derived from MBTH: a bridging peroxide, 2,2′-peroxybis(3-methyl-2,3-dihydrobenzothiazole) (MBTPO), adding to a previously observed azine, 1,2-bis(3-methyl-2,3-dihydrobenzothiazole-2-ylidene)hydrazine (MBTA), and also a small amount of ketone, 3-methyl-2(3H)-benzothiazolone (MBTZ). We suggest that dioxygen is activated to the intermediates, superoxohemin ([FeIII–OO]•) and peroxohemin ([FeIII–OO]−). Because the addition of reactive oxygen species quenchers such as superoxide dismutase (SOD) and catalase allows reaction that prevents the degradation of heme, the roles of liberated superoxide or hydrogen peroxide are excluded from the mechanism. On the other hand, another possible intermediate, a high-valent oxoiron species ([Fe+=O]), is suggested to form the ketone, MBTZ, while under anaerobic conditions organic hydroperoxide (t-BuOOH) instead of O2 solely reacts to form the ketone. The system is discussed in relation to NADPH oxidase, cytochrome P450, NO synthase (NOS), and heme oxidase (HO).
Alkali-Metal Ion Catalysis and Inhibition in Nucleophilic Displacement Reaction of O-Ethyl O-4-Nitrophenyl Phenylphosphonothioate with Alkali-Metal Ethoxides
Authors: Um Ik-Hwan , Kang Ji-Sun , Shin Minah 
Published: March 2013

Abstract
A kinetic study on nucleophilic displacement reactions of O-ethyl O-4-nitrophenyl phenylphosphonothioate (an insecticide called EPN) with alkali-metal ethoxides (EtOM; M = Li, Na, K, and K/18-crown-6-ether) is reported. Dissection of pseudo-first-order rate constant (kobsd) into the second-order rate constants for the reaction of EPN with the dissociated EtO− (kEtO-) and ion-paired EtOM (kEtOM) has revealed that the reactivity increases in the order kEtOLi &lt; kEtO- &lt; kEtONa &lt; kEtOK &lt; kEtOK/18-crown-6-ether, indicating that Li+ inhibits the reaction while the other M+ ions behave as a Lewis acid catalyst in the order Na+ &lt; K+ &lt; 18C6-complexed K+. The contrasting M+ ion effects have been explained in terms of the hard and soft acids and bases (HSAB) principle, since EPN, as a polarizable P=S centered electrophile, would exert a weak interaction with Li+ (a hard acid) but a strong interaction with the 18C6-complexed K+ ion (a soft acid). M+ ions catalyze the current reaction by increasing the electrophilicity of the reaction center. EPN is less reactive than O-4-nitrophenyl diphenylphosphinothioate but is more reactive than O-4-nitrophenyl O,O-diethyl thiophosphate. Factors governing the reactivity of these P=S centered electrophiles are discussed.
A New Facile Two-Step Synthetic Procedure of 1,1′-Diaminoferrocene
Authors: Abdulmalic Mohammad A , Rüffer Tobias 
Published: March 2013

Abstract
1,1′-Diaminoferrocene (3) was conveniently synthesized by employing a Gabriel synthesis in two steps starting from 1,1′-dibromoferrocene (1). Compound 1 was reacted with 2.5 equivalents of phthalimide in the presence of Cu2O using 4-picoline as a solvent to give 1,1′-diphthalimidoferrocene (2) in a moderate yield. Hydrazinolysis of 2 in EtOH afforded 3 in good yields of ca. 70%. The subsequent reaction of 3 with two equivalents of ethyloxalyl chloride in THF gave the diethyl ester of N,N′-ferrocenylene bis(oxamic acid) (1,1′-fcbaH2Et2, 4). The solution obtained by treating 4 with two equivalents of n-Bu4NOH in H2O was added to a solution of Pd(AcO)2 in THF to give the palladium complex [n-Bu4N]2[Pd(1,1′-fcba)] (5) in ca. 80% yield. The compounds 2–4 were characterized by 1H, 13C NMR and IR spectroscopy as well as elemental analysis and the heterobinuclear complex 5 by 1H NMR and IR spectroscopy, elemental analysis and by a single-crystal X-ray diffraction study.