bluuebunny/crossref_metadata_2025 huggingface dataset:
The pro-atherogenic effects of macrophages are reduced upon formation of a complex between C-reactive protein and lysophosphatidylcholine
Authors: Chang Mi-Kyung , Hartvigsen Karsten , Ryu Jewon , Kim Yuna , Han Ki Hoon
Published: October 2012

Rationale

C-reactive protein (CRP) and lysophosphatidylcholine (LPC) are phosphorylcholine-(PC)-containing oxidized phospholipids (oxPLs) found in oxidized LDL (oxLDL), which trigger pro-atherogenic activities of macrophages during the process of atherosclerosis. It has been previously reported that CRP binds to the PC head group of oxLDL in a calcium-dependent manner. The aim of this study was to investigate the importance of binding between CRP and LPC to the pro-atherogenic activities of macrophages.

Objectives and findings

A chemiluminescent immunoassay and HPLC showed that human recombinant CRP formed a stable complex with LPC in the presence of calcium. The Kd value of the binding of the CRP-LPC complex to the receptors FcγRIA or FcγRIIA was 3–5 fold lower than that of CRP alone. The CRP-LPC complex triggered less potent generation of reactive oxygen species and less activation of the transcription factors AP-1 and NF-kB by human monocyte-derived macrophages in comparison to CRP or LPC alone. However, CRP did not affect activities driven by components of oxLDL lacking PC, such as upregulation of PPRE, ABCA1, CD36 and PPARγ and the enhancement of cholesterol efflux by human macrophages. The presence of CRP inhibited the association of Dil-labelled oxLDL to human macrophages.

Conclusions

The formation of complexes between CRP and PC-containing oxPLs, such as LPC, suppresses the pro-atherogenic effects of CRP and LPC on macrophages. This effect may in part retard the progression of atherosclerosis.
The defense response in Arabidopsis thaliana against Fusarium sporotrichioides
Authors: Asano Tomoya , Kimura Makoto , Nishiuchi Takumi
Published: October 2012

Background

Certain graminaceous plants such as Zea mays and Triticum aestivum serve as hosts for Fusarium sporotrichioides; however, molecular interactions between the host plants and F. sporotrichioides remain unknown. It is also not known whether any interaction between Arabidopsis thaliana and F. sporotrichioides can occur. To understand these interactions, we performed proteomic analysis.

Results

Arabidopsis leaves and flowers were inoculated with F. sporotrichioides. Accumulation of PLANT DEFENSIN1.2 (PDF1.2) and PATHOGENESIS RELATED1 (PR1) mRNA in Arabidopsis were increased by inoculation of F. sporotrichioides. Furthermore, mitogen-activated protein kinase 3 (MPK3) and mitogen-activated protein kinase 6 (MPK6), which represent MAP kinases in Arabidopsis, were activated by inoculation of F. sporotrichioides. Proteomic analysis revealed that some defense-related proteins were upregulated, while the expression of photosynthesis- and metabolism-related proteins was down regulated, by inoculation with F. sporotrichioides. We carried out the proteomic analysis about upregulated proteins by inoculation with Fusarium graminearum. The glutathione S-transferases (GSTs), such as GSTF4 and GSTF7 were upregulated, by inoculation with F. graminearum-infected Arabidopsis leaves. On the other hand, GSTF3 and GSTF9 were uniquely upregulated, by inoculation with F. sporotrichioides.

Conclusions

These results indicate that Arabidopsis is a host plant for F. sporotrichioides. We revealed that defense response of Arabidopsis is initiated by infection with F. sporotrichioides.
Comparison of the OHIP-14 and GOHAI as measures of oral health among elderly in Lebanon
Authors: El Osta Nada , Tubert-Jeannin Stephanie , Hennequin Martine , Bou Abboud Naaman Nada , El Osta Lana , Geahchan Negib
Published: October 2012

Background

The respective abilities of the GOHAI and OHIP-14 to discriminate between aged patients with different levels of oral diseases have rarely been studied in developing countries. The aim of this study was to compare the discriminative abilities of the OHIP-14 and the GOHAI in an elderly Lebanese population, and particularly to identify persons with different masticatory function.

Methods

A sample of elderly, aged 65 years or more, living independently was recruited in two primary care offices in Beirut, Lebanon. Data were collected by means of personal interview and clinical examination. The Arabic OHIP-14 and GOHAI questionnaires were used after cultural adaptation for use in Lebanon. The internal consistency, reproducibility and concurrent validity were verified. To test their discriminative abilities, the ADD (GOHAI and OHIP) and SC (GOHAI and OHIP) scores were dichotomized according to the 25thand 75thpercentile respectively and logistic regressions were conducted using socio-demographic, clinical and subjective explanatory variables.

Results

Two hundred and six participants were included; mean age was 72 years and 60% were women. Good psychometric properties were observed for both questionnaires for internal consistency (Cronbach’s alpha>0.88), reproducibility (ICC>0.86) and concurrent validity. Strong correlations were found between GOHAI and OHIP-14 scores but a high prevalence of subjects with no impact was observed using the OHIP-14. Both questionnaires were able to discriminate between participants according to age, perception of temporomandibular joint (TMJ) pain or functional status as represented by the number of dental Functional Units (FU). GOHAI was more discriminant since it identified participants with high dental care needs: high numbers of decayed teeth, low numbers of teeth and socially deprived status.

Conclusions

Lebanese elderly with high dental care needs and impaired oral health were identified more easily with the GOHAI. These results may guide the choice of dental indicators to use in a national geriatric survey.
Nasolabial flap reconstruction in oral cancer
Authors: Singh Seema , Singh Rajesh Kumar , Pandey Manoj
Published: October 2012

Background

The nasolabial flap is a simple flap used for reconstructing small intraoral defects created after the excision of malignant tumors.

Methods

A retrospective analysis of 26 cases of oral cancer treated with primary excision and nasolabial flap reconstruction was carried out. In 22 cases, the excision was combined with neck dissection and facial artery ligation.

Results

Good cosmetic and functional results were obtained in almost all cases. Wound dehiscence developed in three patients, while one patient developed a persistent orocutaneous fistula. Disease recurrence occurred in one patient.

Conclusions

The nasolabial flap is a good flap for the reconstruction of small oral defects after excision of primary tumors and results in good overall cosmetic and functional outcome.
Primary gastric cancer presenting with a metastatic embolus in the common carotid artery: a case report
Authors: Zhang Ying , Zhang Xiu-feng , Shentu Wei-hui , Yang Guan-gen , Shen Zhong , Huang Pin-tong
Published: October 2012

Although about 30% of gastric cancers have distant metastasis at the time of initial diagnosis, metastatic tumor embolus in the main blood vessels is not common, especially in the main artery. The report presents, for the first time, an extremely rare clinical case of a metastatic embolus in the common carotid artery (CCA) from primary gastric cancer. Metastatic embolus from the primary tumor should be considered when patients present with gastric cancer accompanied by intravascular emboli. The patient should be actively examined further so as to allow early detection and treatment.
Estrous cycle-dependent changes of Fas expression in the bovine corpus luteum: influence of keratin 8/18 intermediate filaments and cytokines
Authors: Duncan Alice , Forcina Jennifer , Birt Alyssa , Townson David
Published: October 2012

Background

Fas expression and Fas-induced apoptosis are mechanisms attributed to the selective destruction of cells of the corpus luteum (CL) during luteal regression. In certain cell-types, sensitivity to these death-inducing mechanisms is due to the loss or cleavage of keratin-containing intermediate filaments. Specifically, keratin 8/18 (K8/K18) filaments are hypothesized to influence cell death in part by regulating Fas expression at the cell surface.

Methods

Here, Fas expression on bovine luteal cells was quantified by flow cytometry during the early (Day 5, postovulation) and late stages (Days 16–18, postovulation) of CL function, and the relationship between Fas expression, K8/K18 filament expression and cytokine-induced cell death in vitro was evaluated.

Results

Both total and cell surface expression of Fas on luteal cells was greater for early versus late stage bovine CL (89% vs. 44% of cells for total Fas; 65% vs.18% of cells for cell surface Fas; respectively, P<0.05, n=6-9 CL/stage). A similar increase in the steady-state concentration of mRNA for Fas, as detected by quantitative real-time polymerase chain reaction, however, was not observed. Transient disruption of K8/K18 filaments in the luteal cells with acrylamide (5 mM), however, had no effect on the surface expression of Fas (P>0.05, n=4 CL/stage), despite evidence these conditions increased Fas expression on HepG2 cells (P<0.05, n= 3 expts). Exposure of the luteal cells to cytokines induced cell death (P<0.05) as expected, but there was no effect of K8/K18 filament disruption by acrylamide (P>0.05) or stage of CL (P>0.05, n= 4 CL/stage) on this outcome.

Conclusion

In conclusion, we rejected our null hypothesis that the cell surface expression of Fas does not differ between luteal cells of early and late stage CL. The results also did not support the idea that K8/K18 filaments influence the expression of Fas on the surface of bovine luteal cells. Potential downstream effects of these filaments on death signaling, however, remain a possibility. Importantly, the elevated expression of Fas observed on cells of early stage bovine CL compared to late stage bovine CL raises a provocative question concerning the physiological role(s) of Fas in the corpus luteum, particularly during early luteal development.
High expression of p300 is linked to aggressive features and poor prognosis of Nasopharyngeal Carcinoma
Authors: Liao Zhi-Wei , Zhou Tong-Chong , Tan Xiao-Jun , Song Xian-Lu , Liu Yuan , Shi Xing-Yuan , Huang Wen-Jin , Du Li-Li , Tu Bo-Jun , Lin Xiao-dan
Published: October 2012

Background

Increased expression of transcriptional coactivator p300 has been observed in a variety of human cancers. However, the expression status of p300 protein/mRNA in nasopharyngeal carcinoma (NPC) tissues and its clinicopathologic/prognostic implication are poorly understood.

Methods

In our study, mRNA and protein expression levels of p300 was explored by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC) in nasopharyngeal mucosal and NPC tissues. The data were analyzed by receiver operating characteristic (ROC) curve analysis, spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model.

Results

Up-regulated expression ofp300mRNA/p300 protein was detected in NPC tissues by RT-PCR and WB, when compared to nasopharyngeal mucosal tissues. Based on ROC curve analysis, the cutoff score for p300 high expression was defined when more than 35% of the tumor cells were positively stained. High expression of p300 was observed in 127/209 (60.7%) of NPCs. In NPCs, high expression of p300 was positively associated with later T classification, later N classification, distant metastasis and later clinical stage (P < 0.05). In univariate survival analysis, overexpression of p300 was found to be an indicator of progression-free (P = 0.002) and overall survival (P = 0.001) in NPCs. More importantly, p300 expression was evaluated as an independent prognostic factor for NPC in multivariate analysis (P = 0.036).

Conclusions

Our findings support that high expression of p300 protein might be important in conferring a more aggressive behavior, and is an independent molecular marker for shortened survival time of patients with NPC.
Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: How markers of β-cell loss may assist
Authors: Neutzsky-Wulff Anita V , Andreassen Kim V , Hjuler Sara T , Feigh Michael , Bay-Jensen Anne-Christine , Zheng Qinlong , Henriksen Kim , Karsdal Morten A
Published: October 2012

Disease heterogeneity is as major issue in Type II Diabetes Mellitus (T2DM), and this patient inter-variability might not be sufficiently reflected by measurements of glycated haemoglobin (HbA1c).

Β-cell dysfunction and β-cell death are initiating factors in development of T2DM. In fact, β-cells are known vanish prior to the development of T2DM, and autopsy of overt T2DM patients have shown a 60% reduction in β-cell mass.

As the decline in β-cell function and mass have been proven to be pathological traits in T2DM, methods for evaluating β-cell loss is becoming of more interest. However, evaluation of β-cell death or loss is currently invasive and unattainable for the vast majority of diabetes patients. Serological markers, reflecting β-cell loss would be advantageous to detect and monitor progression of T2DM. Biomarkers with such capacities could be neo-epitopes of proteins with high β-cell specificity containing post translational modifications. Such tools may segregate T2DM patients into more appropriate treatment groups, based on their β-cell status, which is currently not possible. Presently individuals presenting with adequately elevated levels of both insulin and glucose are classified as T2DM patients, while an important subdivision of those is pending, namely those patients with sufficient β-cell capacity and those without. This may warrant two very different treatment options and patient care paths.

Serological biomarkers reflecting β-cell health status may also assist development of new drugs for T2DM and aid physicians in better characterization of individual patients and tailor individual treatments and patient care protocols.
Wetting layer evolution and its temperature dependence during self-assembly of InAs/GaAs quantum dots
Authors: Zhang Hongyi , Chen Yonghai , Zhou Guanyu , Tang Chenguang , Wang Zhanguo
Published: October 2012

For InAs/GaAs(001) quantum dot (QD) system, the wetting layer (WL) evolution and its temperature dependence were studied using reflectance difference spectroscopy and were analyzed with a rate equation model. WL thicknesses showed a monotonic increase at relatively low growth temperatures but showed an initial increase and then decrease at higher temperatures, which were unexpected from a thermodynamic understanding. By adopting a rate equation model, the temperature dependence of QD formation rate was assigned as the origin of different WL evolutions. A brief discussion on the indium desorption was given. Those results gave hints of the kinetic aspects of QD self-assembly.
Well-width dependence of the emission linewidth in ZnO/MgZnO quantum wells
Authors: Lv Xue-Qin , Zhang Jiang-Yong , Ying Lei-Ying , Liu Wen-Jie , Hu Xiao-Long , Zhang Bao-Ping , Qiu Zhi-Ren , Kuboya Shigeyuki , Onabe Kentaro
Published: October 2012

Photoluminescence (PL) spectra were measured as a function of well width (L
W) and temperature in ZnO/Mg0.1Zn0.9O single quantum wells (QWs) with graded thickness. The emission linewidth (full width at half maximum) was extracted from the emission spectra, and its variation as a function of L
W was studied. The inhomogeneous linewidth obtained at 5 K was found to decrease with increasing L
W from 1.8 to 3.3 nm due to the reduced potential variation caused by the L
W fluctuation. Above 3.3 nm, however, the linewidth became larger with increasing L
W, which was explained by the effect related with defect generation due to strain relaxation and exciton expansion in the QW. For the homogenous linewidth broadening, longitudinal optical (LO) phonon scattering and impurity scattering were taken into account. The LO phonon scattering coefficient Γ
LO and impurity scattering coefficient Γ
imp were deduced from the temperature dependence of the linewidth of the PL spectra. Evident reduction of Γ
LO with decreasing L
W was observed, which was ascribed to the confinement-induced enhancement of the exciton binding energy. Different from Γ
LO, a monotonic increase in Γ
imp was observed with decreasing L
W, which was attributed to the enhanced penetration of the exciton wave function into the barrier layers.
A distributed message in message aware concurrent transmission protocol in IEEE 802.11 WLANs
Authors: Kang Young-myoung , Yoo Joon , Lee Joonsoo , Kim Chong-kwon
Published: October 2012

The IEEE 802.11 distributed coordination function (DCF) employs the carrier sense technology to avoid frame collisions. However, recent measurement studies demonstrate that the physical layer (PHY) capture effect frequently occurs; even when frames collide, one of them can be decoded successfully if its relative signal strength is high enough. Furthermore, a new wireless PHY technology, called Message In Message (MIM), adopts an advanced preamble detection function to enhance the PHY capture effect. To fully exploit MIM in multi-collision environments, frame transmission orders have to be carefully scheduled. It also requires tight time synchronization at multiple access points (APs), thus induces large overheads. In this article, we propose an opportunistic concurrent transmission protocol called
D

istributed
O pportunistic M IM-aware C oncurrent T ransmission (DOMCT) which exploits the MIM functionality in a distributed manner obliterating the centralized control. In DOMCT, APs first prepare interference MAPs to discover the possible simultaneous MIM transmission opportunities. Detecting the inadvertent frame transmission from a neighboring AP, an AP transmits another frame intentionally if both frames can successfully be decoded at destination nodes by the MIM capture effect. Through both analysis and extensive ns-2 simulations, we show that DOMCT outperforms the legacy DCF by up to 61% and observe comparable performance to that of the centralized approach.
Layered multimedia broadcast using rateless codes with progressive recovery over cooperative MIMO
Authors: Chen Zhao , Yin Liuguo , Xu Mai , Lu Jianhua
Published: October 2012

This article proposes a novel scheme, based on unequal error protected rateless codes, for broadcasting layered multimedia over cooperative multiple-input multiple-output (MIMO). By taking advantage of both cooperation and broadcasting, we first present a two-phase cooperative MIMO broadcast scheme, which exploits distributed diversity in point-to-multipoint communication scenarios. Then, to enhance layered multimedia transmission with progressive recovery, the progressive rateless codes (PRC) is proposed to recover the layered data according to their importance at the expected received ratio of all output packets. Thus, receivers with different packet loss rate can achieve an adaptive recovery of the layered multimedia progressively. Furthermore, based on PRC, a distortion-based layered multimedia broadcast problem is formulated, which optimizes source bitrate of the layered multimedia and coding rates of PRC to improve the quality of experience (QoE) of the multimedia delivery over all receivers. The performance analysis including both analytical results and simulation experiments of Motion-JPEG 2000 broadcast to receivers verifies the superiority of the cooperative broadcast and efficiency of the QoE-driven optimization algorithm.
Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA)-4-dependent recruitment of nitric oxide-producing macrophages
Authors: Getts Daniel R , Terry Rachael L , Getts Meghann Teague , Müller Marcus , Rana Sabita , Deffrasnes Celine , Ashhurst Thomas Myles , Radford Jane , Hofer Markus , Thomas Shane , Campbell Iain L , King Nicholas JC
Published: October 2012

Infiltration of Ly6Chi monocytes from the blood is a hallmark of viral encephalitis. In mice with lethal encephalitis caused by West Nile virus (WNV), an emerging neurotropic flavivirus, inhibition of Ly6Chi monocyte trafficking into the brain by anti-very late antigen (VLA)-4 integrin antibody blockade at the time of first weight loss and leukocyte influx resulted in long-term survival of up to 60% of infected mice, with subsequent sterilizing immunity. This treatment had no effect on viral titers but appeared to be due to inhibition of Ly6Chi macrophage immigration. Although macrophages isolated from the infected brain induced WNV-specific CD4+ T-cell proliferation, T cells did not directly contribute to pathology, but are likely to be important in viral control, as antibody-mediated T-cell depletion could not reproduce the therapeutic benefit of anti-VLA-4. Instead, 70% of infiltrating inflammatory monocyte-derived macrophages were found to be making nitric oxide (NO). Furthermore, aminoguanidine-mediated inhibition of induced NO synthase activity in infiltrating macrophages significantly prolonged survival, indicating involvement of NO in the immunopathology. These data show for the first time the therapeutic effects of temporally targeting pathogenic NO-producing macrophages during neurotropic viral encephalitis.
Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome
Authors: Song Hongshuo , Pavlicek Jeffrey W , Cai Fangping , Bhattacharya Tanmoy , Li Hui , Iyer Shilpa S , Bar Katharine J , Decker Julie M , Goonetilleke Nilu , Liu Michael KP , Berg Anna , Hora Bhavna , Drinker Mark S , Eudailey Josh , Pickeral Joy , Moody M Anthony , Ferrari Guido , McMichael Andrew , Perelson Alan S , Shaw George M , Hahn Beatrice H , Haynes Barton F , Gao Feng
Published: October 2012

Background

A modest change in HIV-1 fitness can have a significant impact on viral quasispecies evolution and viral pathogenesis, transmission and disease progression. To determine the impact of immune escape mutations selected by cytotoxic T lymphocytes (CTL) on viral fitness in the context of the cognate transmitted/founder (T/F) genome, we developed a new competitive fitness assay using molecular clones of T/F genomes lacking exogenous genetic markers and a highly sensitive and precise parallel allele-specific sequencing (PASS) method.

Results

The T/F and mutant viruses were competed in CD4+ T-cell enriched cultures, relative proportions of viruses were assayed after repeated cell-free passage, and fitness costs were estimated by mathematical modeling. Naturally occurring HLA B57-restricted mutations involving the TW10 epitope in Gag and two epitopes in Tat/Rev and Env were assessed independently and together. Compensatory mutations which restored viral replication fitness were also assessed. A principal TW10 escape mutation, T242N, led to a 42% reduction in replication fitness but V247I and G248A mutations in the same epitope restored fitness to wild-type levels. No fitness difference was observed between the T/F and a naturally selected variant carrying the early CTL escape mutation (R355K) in Env and a reversion mutation in the Tat/Rev overlapping region.

Conclusions

These findings reveal a broad spectrum of fitness costs to CTL escape mutations in T/F viral genomes, similar to recent findings reported for neutralizing antibody escape mutations, and highlight the extraordinary plasticity and adaptive potential of the HIV-1 genome. Analysis of T/F genomes and their evolved progeny is a powerful approach for assessing the impact of composite mutational events on viral fitness.
Identification of novel CDK9 and Cyclin T1-associated protein complexes (CCAPs) whose siRNA depletion enhances HIV-1 Tat function
Authors: Ramakrishnan Rajesh , Liu Hongbing , Donahue Hart , Malovannaya Anna , Qin Jun , Rice Andrew P
Published: October 2012

Background

HIV-1 Tat activates RNA Polymerase II (RNAP II) elongation of the integrated provirus by recruiting a protein kinase known as P-TEFb to TAR RNA at the 5′end of nascent viral transcripts. The catalytic core of P-TEFb contains CDK9 and Cyclin T1 (CCNT1). A human endogenous complexome has recently been described – the set of multi-protein complexes in HeLa cell nuclei. We mined this complexome data set and identified 12 distinct multi-protein complexes that contain both CDK9 and CCNT1. We have termed these complexes CCAPs forCDK9/CCNT1-associatedprotein complexes. Nine CCAPs are novel, while three were previously identified as Core P-TEFb, the 7SK snRNP, and the Super-Elongation Complex. We have investigated the role of five newly identified CCAPs in Tat function and viral gene expression.

Results

We examined five CCAPs that contain: 1) PPP1R10/TOX3/WDR82; 2) TTF2; 3) TPR; 4) WRNIP1; 5) FBXO11/CUL1/SKP1. SiRNA depletions of protein subunits of the five CCAPs enhanced Tat activation of an integrated HIV-1 LTR-Luciferase reporter in TZM-bl cells. Using plasmid transfection assays in HeLa cells, we also found that siRNA depletions of TTF2, FBXO11, PPP1R10, WDR82, and TOX3 enhanced Tat activation of an HIV-1 LTR-luciferase reporter, but the depletions did not enhance expression of an NF-κB reporter plasmid with the exception of PPP1R10. We found no evidence that depletion of CCAPs perturbed the level of CDK9/CCNT1 in the 7SK snRNP. We also found that the combination of siRNA depletions of both TTF2 and FBXO11 sensitized a latent provirus in Jurkat cells to reactivation by sub-optimal amounts of αCD3/CD28 antibodies.

Conclusions

Our results identified five novel CDK9/CCNT1 complexes that are capable of negative regulation of HIV-1 Tat function and viral gene expression. Because siRNA depletions of CCAPs enhance Tat function, it is possible that these complexes reduce the level of CDK9 and CCNT1 available for Tat, similar to the negative regulation of Tat by the 7SK snRNP. Our results highlight the complexity in the biological functions of CDK9 and CCNT1.
An improved respiratory syncytial virus neutralization assay based on the detection of green fluorescent protein expression and automated plaque counting
Authors: van Remmerden Yvonne , Xu Fang , van Eldik Mandy , Heldens Jacco GM , Huisman Willem , Widjojoatmodjo Myra N
Published: October 2012

Background

Virus neutralizing antibodies against respiratory syncytial virus (RSV) are considered important correlates of protection for vaccine evaluation. The established plaque reduction assay is time consuming, labor intensive and highly variable.

Methods

Here, a neutralization assay based on a modified RSV strain expressing the green fluorescent protein in combination with automated detection and quantification of plaques is described.

Results

The fluorescence plaque reduction assay in microplate format requires only two days to complete and is simple and reproducible. A good correlation between visual and automated counting methods to determine RSV neutralizing serum antibody titers was observed.

Conclusions

The developed virus neutralization assay is suitable for high-throughput testing and can be used for both animal studies and (large scale) vaccine clinical trials.
Acute risk for hepatitis E virus infection among HIV-1-positive pregnant women in central Africa
Authors: Caron Mélanie , Bouscaillou Julie , Kazanji Mirdad
Published: October 2012

Background

Hepatitis E virus (HEV), an enterically transmitted pathogen, is highly endemic in several African countries. Pregnant women are at particularly high risk for acute or severe hepatitis E. In Gabon, a central African country, the prevalence of antibodies to HEV among pregnant women is 14.1%. Recent studies have demonstrated unusual patterns of hepatitis E (chronic hepatitis, cirrhosis) among immunodeficient patients.

Findings

We investigated the prevalence of antibodies to HEV among pregnant women infected with HIV-1 or HTLV-1 in Gabon. Of 243 samples collected, 183 were positive for HIV-1 and 60 for HTLV-1; 16 women (6.6%) had IgG antibodies to HEV. The seroprevalence was higher among HIV-1-infected women (7.1%) than HTLV-1-infected women (5.0%). Moreover, the HIV-1 viral load was significantly increased (p ≤ 0.02) among women with past-HEV exposure (1.3E+05 vs 5.7E+04 copies per ml), whereas no difference was found in HTLV-1 proviral load (9.0E+01 vs 1.1E+03 copies per ml).

Conclusions

These data provide evidence that HIV-1-infected women are at risk for acute or severe infection if they are exposed to HEV during pregnancy, with an increased viral load.
Human Papillomavirus (HPV) genotype 18 variants in patients with clinical manifestations of HPV related infections in Bilbao, Spain
Authors: Arroyo Sara L , Basaras Miren , Arrese Elixabete , Hernáez Silvia , Andía Daniel , Esteban Valentín , Garcia-Etxebarria Koldo , Jugo Begoña M , Cisterna Ramón
Published: November 2012

Background

Human papillomavirus (HPV) variants differ in their biological and chemical properties, and therefore, may present differences in pathogenicity. Most authors classified variants based on the phylogenetic analysis of L1 region. Nevertheless, recombination in HPV samples is becoming a usual finding and thus, characterizing genetic variability in other regions should be essential.

Objectives

We aimed to characterize the genetic variability of HPV 18 in 5 genomic regions: E6, E7, E4, L1 and the Upstream Regulatory Region (URR), working with both single infection and multiple HPV infection samples. Furthermore, we aimed to assess the prevalence of HPV 18 variants in our region and look for possible existence of recombination as well as analyze the relationship between these variants and the type of lesion.

Methods

From 2007 to 2010, Clinical Microbiology and Infection Control Department analyzed 44 samples which were positive for HPV 18. Genetic variability was determined in PCR products and variants were assigned to European, Asian-amerindian or African lineage. Recombination and association of variants with different types of lesion was studied.

Results

Genetic analysis of the regions revealed a total of 56 nucleotide variations. European, African and Asian-amerindian variants were found in 25/44 (56.8%), 10/44 (22.7%) and 5/44 (11.4%) samples, respectively. We detected the presence of recombinant variants in 2/44 (4.5%) cases. Samples taken from high-grade squamous intraepithelial lesions (H-SIL) only presented variants with specific-african substitutions.

Conclusions

Multiple HPV infection, non-european HPV variants prevalence and existence of recombination are considered risk factors for HPV persistence and progression of intraepithelial abnormalities, and therefore, should be taken into consideration in order to help to design and optimize diagnostics protocols as well as improve epidemiologic studies.

Our study is one of the few studies in Spain which analyses the genetic variability of HPV18 and we showed the importance of characterizing more than one genomic region in order to detect recombination and classify HPV variants properly.
Comparisons of the iron deficient metabolic response in rats fed either an AIN-76 or AIN-93 based diet
Authors: Davis McKale R , Hester Kristen K , Shawron Krista M , Lucas Edralin A , Smith Brenda J , Clarke Stephen L
Published: October 2012

Background

Previous studies examining the metabolic consequences of dietary iron deficiency have reported elevated serum glucose concentrations in iron-deficient animals. Importantly, the majority of these findings were observed using an earlier version of a laboratory animal diet (AIN-76A) in which the primary carbohydrate source was sucrose – a disaccharide known to negatively impact both glucose and lipid homeostasis. The AIN-76A diet formula was improved in 1993 (AIN-93) to optimize animal nutrition with a major change being the substitution of cornstarch for sucrose. Therefore, we sought to examine the effects of iron deficiency on steady-state glucose homeostasis and the hepatic expression of glucose- and lipid-related genes in rats fed an iron-deficient diet based on either an AIN-76A or AIN-93 diet.

Methods

The study design consisted of 6 treatment groups: control (C; 40 mg Fe/kg diet), iron deficient (ID; ≤ 3 mg Fe/kg diet), or pair-fed (PF; 40 mg Fe/kg) fed either an AIN-76A or AIN-93 diet for 21 d. Hemoglobin and hematocrit were measured in whole blood. Serum insulin and cortisol were measure by ELISA. Serum glucose and triacylglycerols were measured by standard colorimetric enzyme assays. Alterations in hepatic gene expression were determined by real-time qPCR.

Results

Hemoglobin and hematocrit were significantly reduced in both ID groups compared to the C and PF groups. Similarly, animals in the both ID groups exhibited elevated steady-state levels of blood glucose and insulin, and significantly decreased levels of circulating cortisol compared to their respective PF controls. Serum triacyglycerols were only increased in ID animals consuming the AIN-76A diet. Hepatic gene expression analyses revealed a ~4- and 3-fold increase in the expression of glucokinase and pyruvate dehydrogenase kinase-4 mRNA, respectively, in the ID group on either diet compared to their respective PF counterparts. In contrast, the expression of lipogenic genes was significantly elevated in the AIN-76 ID group, while expression of these genes was unaffected by iron status in the AIN-93 ID group.

Conclusions

These results indicate that an impaired iron status is sufficient to alter glucose homeostasis, though alterations in lipid metabolism associated with ID are only observed in animals receiving the AIN-76A diet.
Association of adipokines and adhesion molecules with indicators of obesity in women undergoing mammography screening
Authors: Isoppo de Souza Caroline , Rosa Daniela Dornelles , Ettrich Betina , Cibeira Gabriela Hermann , Giacomazzi Juliana , Tusset Paloma , Ashton-Prolla Patrícia , Medeiros Lidia Rosi , Caleffi Maira , Neto Eurico Camargo , Moriguchi Emilio Hideyuki , Graudenz Marcia Silveira
Published: October 2012

Background

The soluble cell adhesion molecules and adipokines are elevated in patients with obesity, hypertension, type 2 diabetes mellitus, breast cancer and atherosclerosis.

Objective

To investigate the relationship between anthropometric profile, dietary intake, lipid profile and fasting glycemia with serum levels of adipokines (adiponectin and PAI-1) and adhesion molecules (ICAM-1 and VCAM-1) in women without breast cancer undergoing routine mammographic screening.

Design

Transversal study.

Subjects

One hundred and forty-five women over 40-years old participated in this study.

Results

In 39.3% of cases the BMI was above 30 kg/m2; 46.9% had hypertension, 14.5% had type 2 Diabetes Mellitus, 31.7% had dyslipidemia and 88.3% presented a waist-to-hip ratio ≥ 0.8. A linear correlation was found between serum levels of PAI-1 and triglycerides, between serum levels of PAI-1 and WHR and between serum levels of VCAM-1 and BMI.

Conclusion

We found a high prevalence of obesity and metabolic syndrome. PAI-1 and VCAM-1 levels were correlated with clinical indicators of obesity and overweight.
Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations
Authors: Kroeger Cynthia M , Klempel Monica C , Bhutani Surabhi , Trepanowski John F , Tangney Christine C , Varady Krista A
Published: October 2012

Background

The ability of an intermittent fasting (IF)-calorie restriction (CR) regimen (with or without liquid meals) to modulate adipokines in a way that is protective against coronary heart disease (CHD) has yet to be tested.

Objective

Accordingly, we examined the effects of an IFCR diet on adipokine profile, body composition, and markers of CHD risk in obese women.

Methods

Subjects (n = 54) were randomized to either the IFCR-liquid (IFCR-L) or IFCR-food based (IFCR-F) diet for 10 weeks.

Results

Greater decreases in body weight and waist circumference were noted in the IFCR-L group (4 ± 1 kg; 6 ± 1 cm) versus the IFCR-F group (3 ± 1 kg; 4 ± 1 cm). Similar reductions (P < 0.0001) in fat mass were demonstrated in the IFCR-L (3 ± 1 kg) and IFCR-F group (2 ± 1 kg). Reductions in total and LDL cholesterol levels were greater (P = 0.04) in the IFCR-L (19 ± 10%; 20 ± 9%, respectively) versus the IFCR-F group (8 ± 3%; 7 ± 4%, respectively). LDL peak particle size increased (P < 0.01) in the IFCR-L group only. The proportion of small LDL particles decreased (P < 0.01) in both groups. Adipokines, such as leptin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and insulin-like growth factor-1 (IGF-1) decreased (P < 0.05), in the IFCR-L group only.

Conclusion

These findings suggest that IFCR with a liquid diet favorably modulates visceral fat and adipokines in a way that may confer protection against CHD.
Sexual obsessions and suicidal behaviors in patients with mood disorders, panic disorder and schizophrenia
Authors: Dell’Osso Liliana , Casu Giulia , Carlini Marina , Conversano Ciro , Gremigni Paola , Carmassi Claudia
Published: October 2012

Background

The topic of sexual obsessions as a psychiatric symptom has not been well investigated. The aim of this study was twofold: 1) to explore the presence of sexual obsessions in patients with mood disorders (n=156), panic disorder (n=54) and schizophrenia (n=79), with respect to non-psychiatric subjects (n=100); 2) to investigate the relationship between sexual obsessions and suicidal behaviors, taking into account socio-demographic variables ad mental disorders.

Methods

289 psychiatric patients with mood disorders, panic disorder or schizophrenia, were recruited at the Italian University departments of psychiatry along with 100 non-psychiatric subjects, who presented for a routine eye exam at the ophthalmology department of the same Universities. The assessments included: the Structured Clinical Interview for DSM-IV-TR, the Brief Psychiatric Rating Scale (BPRS), the Obsessive-Compulsive Spectrum Self-Report (OBS-SR), for sexual obsession, and the Mood Spectrum-Self Report lifetime version (MOODS-SR). Suicidality was assessed by means of 6 items of the MOODS-SR.

Results

Sexual obsessions were more frequent in schizophrenia (54.4%), followed by mood disorders (35.9%). Among schizophrenia patients, males reported more sexual obsessions than females (P<0.01). Subjects who were more likely to report suicidal behaviors (suicidal ideation, plans and attempts) were female (adjusted OR=1.99), patients with mental disorders, specifically mood disorders (adjusted OR=11.5), schizophrenia (adjusted OR=3.7) or panic disorder (adjusted OR=2.9), and subjects who reported lifetime sexual obsessions (adjusted OR= 3.6). Sexual obsessions remained independently associated with all aspects of suicidal behaviors. Age, education, marital and employment status were not related to suicidal behaviors.

Conclusions

Special attention should be given to investigate and establish effective strategies of treatment for sexual obsessions, especially those with comorbid mood disorders or schizophrenia.
Transcriptomic markers meet the real world: finding diagnostic signatures of corticosteroid treatment in commercial beef samples
Authors: Pegolo Sara , Gallina Guglielmo , Montesissa Clara , Capolongo Francesca , Ferraresso Serena , Pellizzari Caterina , Poppi Lisa , Castagnaro Massimo , Bargelloni Luca
Published: October 2012

Background

The use of growth-promoters in beef cattle, despite the EU ban, remains a frequent practice. The use of transcriptomic markers has already proposed to identify indirect evidence of anabolic hormone treatment. So far, such approach has been tested in experimentally treated animals. Here, for the first time commercial samples were analyzed.

Results

Quantitative determination of Dexamethasone (DEX) residues in the urine collected at the slaughterhouse was performed by Liquid Chromatography-Mass Spectrometry (LC-MS). DNA-microarray technology was used to obtain transcriptomic profiles of skeletal muscle in commercial samples and negative controls. LC-MS confirmed the presence of low level of DEX residues in the urine of the commercial samples suspect for histological classification. Principal Component Analysis (PCA) on microarray data identified two clusters of samples. One cluster included negative controls and a subset of commercial samples, while a second cluster included part of the specimens collected at the slaughterhouse together with positives for corticosteroid treatment based on thymus histology and LC-MS. Functional analysis of the differentially expressed genes (3961) between the two groups provided further evidence that animals clustering with positive samples might have been treated with corticosteroids. These suspect samples could be reliably classified with a specific classification tool (Prediction Analysis of Microarray) using just two genes.

Conclusions

Despite broad variation observed in gene expression profiles, the present study showed that DNA-microarrays can be used to find transcriptomic signatures of putative anabolic treatments and that gene expression markers could represent a useful screening tool.
Photon activated therapy (PAT) using monochromatic Synchrotron x-rays and iron oxide nanoparticles in a mouse tumor model: feasibility study of PAT for the treatment of superficial malignancy
Authors: Choi Gi-Hwan , Seo Seung-Jun , Kim Ki-Hong , Kim Hong-Tae , Park Sung-Hwan , Lim Jae-Hong , Kim Jong-Ki
Published: October 2012

Background

X-rays are known to interact with metallic nanoparticles, producing photoelectric species as radiosensitizing effects, and have been exploited in vivo mainly with gold nanoparticles. The purpose of this study was to investigate the potential of sensitizing effect of iron oxide nanoparticles for photon activated therapy.

Methods

X-rays photon activated therapy (PAT) was studied by treating CT26 tumor cells and CT26 tumor-bearing mice loaded with 13-nm diameter FeO NP, and irradiating them at 7.1 keV near the Fe K-edge using synchrotron x-rays radiation. Survival of cells was determined by MTT assay, and tumor regression assay was performed for in vivo model experiment. The results of PAT treated groups were compared with x-rays alone control groups.

Results

A more significant reduction in viability and damage was observed in the FeO NP-treated irradiated cells, compared to the radiation alone group (p < 0.04). Injection of FeO NP (100 mg/kg) 30 min prior to irradiation elevated the tumor concentration of magnetite to 40 μg of Fe/g tissue, with a tumor-to-muscle ratio of 17.4. The group receiving FeO NP and radiation of 10 Gy showed 80% complete tumor regression (CTR) after 15–35 days and relapse-free survival for up to 6 months, compared to the control group, which showed growth retardation, resulting in 80% fatality. The group receiving radiation of 40 Gy showed 100% CTR in all cases irrespective of the presence of FeO NP, but CTR was achieved earlier in the PAT-treated group compared with the radiation alone group.

Conclusions

An iron oxide nanoparticle enhanced therapeutic effect with relatively low tissue concentration of iron and 10 Gy of monochromatic X-rays. Since 7.1 keV X-rays is attenuated very sharply in the tissue, FeO NP-PAT may have promise as a potent treatment option for superficial malignancies in the skin, like chest wall recurrence of breast cancer.
Monitoring access to nationally commissioned services in England
Authors: Coles Suzanne , Haire Kate , Kenny Tom , Jessop Edmund G
Published: October 2012

Background

For over 20 years, the National Health Service in England has run a system of national planning for highly specialised healthcare services. The aim is to ensure that very rare diseases are treated, and very complex procedures performed, in only a few centres, each of which maintains a volume high enough to maintain excellent outcomes. The commissioning strategy for the provision of these national services in England is strongly centralising. Centralising does however create a duty to ensure that patients distant from the treatment centres are not thereby disadvantaged. The commissioning process ensures sufficient capacity to treat the entire national caseload of clinically eligible patients. The aim of this paper is to apply the Systematic Component of Variation (SCV) to study access to services commissioned by the National Specialised Commissioning Team (NSCT) in England. The discussion focuses on the potential explanations for a high level of systematic variation between areas and on the use of the SCV to support the monitoring and development of these nationally commissioned services.

Method

Data from nationally commissioned services for the year ending 2011 were received from treating hospital. Mid year age and sex appropriate population estimates were then obtained to provide denominator data. Data were analysed at the geographic level of strategic health authority.

Results

30 services met all requirements for analysis. There is no apparent relationship between SCV and number of locations from which the service is provided. On inspection high SCV is more common among recently commissioned services.

Discussion

The importance of the SCV lies in its ability to support the development of highly specialised services. Once the random variation has been accounted for, the reasons for a systematic component can be explored. While no absolute cut- off exists, the SCV can be used to gauge and explore services that are potentially not covering the national caseload. The reason for a high SCV may not be immediately apparent; thus the SCV can aid those responsible for commissioning the service to seek potential explanations and identify improvements.

Conclusion

We have reviewed spatial variation in access to a set of highly specialised services in England. On inspecting our results, we believe that they suggest that equity of access can usually be achieved at about five years after establishing a service, and this is not dependent, within the geography of England, on the number of centres designated.
Lung nodule detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography in patients with papillary thyroid cancer, negative 131I whole body scan, and undetectable serum-stimulated thyroglobulin levels: two case reports
Authors: Jung Chan-Hee , Goong Hyeon-Jeong , Kim Bo-Yeon , Park Jung-Mi , Kwak Jeong-Ja , Kim Chul-Hee , Hong Hyun-Sook , Kang Sung-Koo , Mok Ji-Oh
Published: October 2012

Introduction

When a pulmonary nodular lesion is detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography in a patient with post-surgical papillary thyroid carcinoma with undetectable serum-stimulated thyroglobulin levels and negative 131I whole body scan, diagnosis and management of the nodule may be confusing.

Case presentation

We describe two post-surgical patients with papillary thyroid carcinoma who showed pulmonary nodular lesions detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography. In both cases serum-stimulated thyroglobulin levels were undetectable and nodular lesions were not detected by 131I whole body scan. In the first case, a 64-year-old Asian woman showed one focal increased fluorodeoxyglucose uptake lesion in the right lower lobe of one of her lungs. Based on the histologic study, the pulmonary nodular lesion was diagnosed as a solitary pulmonary metastasis from papillary thyroid carcinoma. In the second case, a 59-year-old Asian woman showed a new pulmonary nodule in the right lower lobe. The computed tomography scan of her chest revealed a 9mm nodule in the anterior basal segment and another tiny nodule in the posterior basal segment of the right lower lobe. Six months later, both nodules had increased in size and miliary disseminated nodules were also seen in both lungs. Based on their histology, the pulmonary nodular lesions were considered to be primary lung adenocarcinoma.

Conclusions

The present cases emphasize that physicians should be cautious and make efforts for an accurate diagnosis of pulmonary nodules detected on F-18 fluorodeoxyglucose positron emission tomography-computed tomography in patients with papillary thyroid carcinoma with no evidence of metastasis such as negative 131I whole body scan and undetectable stimulated serum thyroglobulin levels.