bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and metabolic analysis of a model microbial community for understanding trophic and electron accepting interactions of subsurface anaerobic environments
Authors: Miller Lance D , Mosher Jennifer J , Venkateswaran Amudhan , Yang Zamin K , Palumbo Anthony V , Phelps Tommy J , Podar Mircea , Schadt Christopher W , Keller Martin
Published: May 2010

Background

Communities of microorganisms control the rates of key biogeochemical cycles, and are important for biotechnology, bioremediation, and industrial microbiological processes. For this reason, we constructed a model microbial community comprised of three species dependent on trophic interactions. The three species microbial community was comprised of Clostridium cellulolyticum, Desulfovibrio vulgaris Hildenborough, and Geobacter sulfurreducens and was grown under continuous culture conditions. Cellobiose served as the carbon and energy source for C. cellulolyticum, whereas D. vulgaris and G. sulfurreducens derived carbon and energy from the metabolic products of cellobiose fermentation and were provided with sulfate and fumarate respectively as electron acceptors.

Results

qPCR monitoring of the culture revealed C. cellulolyticum to be dominant as expected and confirmed the presence of D. vulgaris and G. sulfurreducens. Proposed metabolic modeling of carbon and electron flow of the three-species community indicated that the growth of C. cellulolyticum and D. vulgaris were electron donor limited whereas G. sulfurreducens was electron acceptor limited.

Conclusions

The results demonstrate that C. cellulolyticum, D. vulgaris, and G. sulfurreducens can be grown in coculture in a continuous culture system in which D. vulgaris and G. sulfurreducens are dependent upon the metabolic byproducts of C. cellulolyticum for nutrients. This represents a step towards developing a tractable model ecosystem comprised of members representing the functional groups of a trophic network.
Comparison of homoeolocus organisation in paired BAC clones from white clover (Trifolium repens L.) and microcolinearity with model legume species
Authors: Hand Melanie L , Cogan Noel OI , Sawbridge Timothy I , Spangenberg German C , Forster John W
Published: May 2010

Background

White clover (Trifolium repensL.) is an outbreeding allotetraploid species and an important forage legume in temperate grassland agriculture. Comparison of sub-genome architecture and study of nucleotide sequence diversity within allopolyploids provides insight into evolutionary divergence mechanisms, and is also necessary for the development of whole-genome sequencing strategies. This study aimed to evaluate the degree of divergence between the O and P' sub-genomes of white clover through sequencing of BAC clones containing paired homoeoloci. The microsyntenic relationships between the genomes of white clover and the model legumesLotus japonicusandMedicago truncatulaas well asArabidopsis thalianawere also characterised.

Results

A total of four paired homoeologous BACs were selected and sequenced to generate 173 kb of overlapping sequence between the O and P' sub-genomes. Equivalent gene content was generally observed, apart from small-scale deletions, in contrast to conservation of intergenic sequences, which varied between the four selected regions. Measurement of the number of synonymous substitutions between homoeologous genes led to estimation of a 4.2 million year divergence time between the two sub-genomes. Microsynteny was observed between the genomes of white clover andL. japonicusfor all four targeted regions, but correspondingM. truncatulagenomic regions were only identified for two BAC pairs.

Conclusions

This study describes the first analysis of sub-genome structural conservation across selected genomic regions in white clover. Although the high levels of sequence conservation between the O and P' sub-genomes would complicate efforts for whole genome sequence assembly, the conserved microsynteny with model legume genomes, especially that ofL. japonicus, will be highly valuable for the future of white clover genomics and molecular breeding.
Transcriptional regulation of the CRK/DUF26 group of Receptor-like protein kinases by ozone and plant hormones in Arabidopsis
Authors: Wrzaczek Michael , Brosché Mikael , Salojärvi Jarkko , Kangasjärvi Saijaliisa , Idänheimo Niina , Mersmann Sophia , Robatzek Silke , Karpiński Stanisław , Karpińska Barbara , Kangasjärvi Jaakko
Published: May 2010

Background

Plant Receptor-like/Pelle kinases (RLK) are a group of conserved signalling components that regulate developmental programs and responses to biotic and abiotic stresses. One of the largest RLK groups is formed by the Domain of Unknown Function 26 (DUF26) RLKs, also called Cysteine-rich Receptor-like Kinases (CRKs), which have been suggested to play important roles in the regulation of pathogen defence and programmed cell death. Despite the vast number of RLKs present in plants, however, only a few of them have been functionally characterized.

Results

We examined the transcriptional regulation of allArabidopsis CRKsby ozone (O3), high light and pathogen/elicitor treatment - conditions known to induce the production of reactive oxygen species (ROS) in various subcellular compartments. SeveralCRKswere transcriptionally induced by exposure to O3but not by light stress. O3induces an extracellular oxidative burst, whilst light stress leads to ROS production in chloroplasts. Analysis of publicly available microarray data revealed that the transcriptional responses of theCRKsto O3were very similar to responses to microbes or pathogen-associated molecular patterns (PAMPs). Several mutants altered in hormone biosynthesis or signalling showed changes in basal and O3-induced transcriptional responses.

Conclusions

Combining expression analysis from multiple treatments with mutants altered in hormone biosynthesis or signalling suggest a model in which O3and salicylic acid (SA) activate separate signaling pathways that exhibit negative crosstalk. Although O3is classified as an abiotic stress to plants, transcriptional profiling of CRKs showed strong similarities between the O3and biotic stress responses.
Gated myocardial perfusion SPECT underestimates left ventricular volumes and shows high variability compared to cardiac magnetic resonance imaging -- a comparison of four different commercial automated software packages
Authors: Hedeer Fredrik , Palmer John , Arheden Håkan , Ugander Martin
Published: May 2010

Background

We sought to compare quantification of left ventricular volumes and ejection fraction by different gated myocardial perfusion SPECT (MPS) programs with each other and to magnetic resonance (MR) imaging.

Methods

N = 100 patients with known or suspected coronary artery disease were examined at rest with 99 mTc-tetrofosmin gated MPS and cardiac MR imaging. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) were obtained by analysing gated MPS data with four different programs: Quantitative Gated SPECT (QGS), GE MyoMetrix, Emory Cardiac Toolbox (ECTb) and Exini heart.

Results

All programs showed a mean bias compared to MR imaging of approximately -30% for EDV (-22 to -34%, p < 0.001 for all), ESV (-12 to -37%, p < 0.001 for ECTb, p < 0.05 for Exini, p = ns for QGS and MyoMetrix) and SV (-21 to -41%, p < 0.001 for all). Mean bias ± 2 SD for EF (% of EF) was -9 ± 27% (p < 0.01), 6 ± 29% (p = ns), 15 ± 27% (p < 0.001) and 0 ± 28% (p = ns) for QGS, ECTb, MyoMetrix, and Exini, respectively.

Conclusions

Gated MPS, systematically underestimates left ventricular volumes by approximately 30% and shows a high variability, especially for ESV. For EF, accuracy was better, with a mean bias between -15 and 6% of EF. It may be of value to take this into consideration when determining absolute values of LV volumes and EF in a clinical setting.
TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters
Authors: Schneiderman Rosa S , Shmueli Esther , Kirson Eilon D , Palti Yoram
Published: May 2010

Background

Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields - TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin.

Methods

Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line EmtR1; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs.

Results

TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells.

Conclusions

The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors.
The radiosensitization effects of Endostar on human lung squamous cancer cells H-520
Authors: You Zhen Y , Zhao Yong , Liu Feng , Zhang Ying D , Wang Jun J
Published: May 2010

Background

The present study mainly aimed to investigate the direct effects of Endostar (ES) on the proliferation and radiosensitivity of human lung squamous cancer cell line H-520.

Results

ES significantly inhibited H-520 cell proliferation in a time- and dose-dependent manner. According to the colony-forming assays, ES could increase the H-520 cell radiosensitivity. ES induced cell apoptosis, the apoptosis rate increased with the raise of ES concentration. Irradiation induced significantly higher apoptosis rate in ES-treated H-520 cells than non-treated H-520 cells. ES induced cell cycle distribution and G0/G1 arrest in H-520 cells, whereas irradiation induced G2/M arrest. The phospho-p38-MAPK and p-Akt protein levels were decreased in H-520 cells after ES treatment. Furthermore, activated caspase protein level increased and Bcl-2 protein levels decreased after treatment with ES and irradiation.

Conclusion

ES significantly enhanced the sensitivity of H-520 cells to irradiation by inhibition of cellular proliferation, promotion of cell apoptosis and redistribution of cell cycle, possibly via deactivation of Akt pathway. The present study supports the possibility to use the combination of ES and ionizing irradiation to treat patients with lung squamous cell cancer in clinics.
Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against Plasmodium falciparum
Authors: Parquet Véronique , Henry Maud , Wurtz Nathalie , Dormoi Jerome , Briolant Sébastien , Gil Marine , Baret Eric , Amalvict Rémy , Rogier Christophe , Pradines Bruno
Published: May 2010

Background

Quinine (QN) remains the first line anti-malarial drug for the treatment of complicated malaria in Europe and Africa. The emergence of QN resistance has been documented. QN resistance is not yet a significant problem, but there is an urgent need to discover partners for use in combination with QN. The aim of the study was to assess the in vitro potentiating effects of atorvastatin (AVA), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in combination with QN against Plasmodium falciparum and to evaluate whether the effects of AVA could be associated with gene copy number or mutations in genes involved in QN resistance, such as pfcrt, pfmdr1, pfmrp and pfnhe.

Methods

The susceptibilities to combination of AVA with QN were assessed against 21 parasite strains using the in vitro isotopic microtest. Genotypes and gene copy number were assessed for pfcrt, pfmdr1, pfmdr2, pfmrp genes. In addition, the number of DNNND, DDNHNDNHNN repeats in pfnhe-1 ms4760 and the ms4760 profile were determined for each strains of P. falciparum.

Results

AVA demonstrated synergistic effects in combination with QN against 21 P. falciparum strains. The QN IC50 was reduced by 5% (0% to 15%; 95%CI: 1%-8%), 10% (3% to 23%; 95%CI: 7%-14%) and 22% (14% to 40%; 95%CI: 19%-25%) in presence of AVA at concentrations of 0.1, 0.5 and 1.0 μM, respectively. These reductions were all significant (p < 0.009). The reduction in the QN IC50 in presence of AVA was not significantly correlated with the QN IC50 (r = 0.22, P = 0.3288) or the AVA IC50 (r = 0.03, P = 0.8946). The synergistic effect of AVA in combination with QN was not significantly associated with polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 genes that could be involved in QN resistance. The synergistic effect of AVA on QN responses was not significantly associated with pfmdr1 copy number (P = 0.0428).

Conclusion

The synergistic effect of AVA in combination with QN was found to be unrelated to mutations occurring in transport protein genes involved in QN drug resistance. The different mechanisms of drug uptake and/or mode of action for AVA compared to the other anti-malarial drugs, as well as the AVA-mediated synergy of the anti-malarial effect of QN, suggests that AVA will be a good candidate for combinatorial malaria treatment. All of these observations support calls for both an in vivo evaluation with pharmacokinetic component and clinical trials of AVA as an anti-malarial therapy.
Hyponatraemia in imported malaria is common and associated with disease severity
Authors: van Wolfswinkel Marlies E , Hesselink Dennis A , Zietse Robert , Hoorn Ewout J , van Genderen Perry JJ
Published: May 2010

Background

Hyponatraemia (serum sodium < 135 mmol/L) has long been recognized as a complication of malaria. However, few studies have been done in non-immune adult populations. It has not been investigated previously how hyponatraemia is distributed among the various Plasmodium species, and its association with malaria severity is unknown.

The aim of this retrospective cohort study was to determine the prevalence of hyponatraemia and its association with malaria severity in a large cohort of patients with imported malaria caused by various Plasmodium species.

Methods

All patients that were diagnosed with malaria in the Harbour Hospital and Institute for Tropical Diseases in Rotterdam in the period 1999-2009 and who had available serum sodium on admission were included. Severe malaria was defined according to the modified WHO criteria. Prevalence of hyponatraemia and its association with malaria severity were investigated by univariate comparison, ROC analysis and multivariate logistic regression analysis.

Results

A total of 446 patients with malaria (severe falciparum malaria n = 35, non-severe falciparum malaria n = 280, non-falciparum malaria n = 131) was included. Hyponatraemia was present in 207 patients (46%). Prevalence and severity of hyponatraemia were greatest in severe falciparum malaria (77%, median serum sodium 129 mmol/L), followed by non-severe falciparum malaria (48%, median serum sodium 131 mmol/L), and non-falciparum malaria (34%, median serum sodium 132 mmol/L). Admission serum sodium < 133 mmol/L had a sensitivity of 0.69 and a specificity of 0.76 for predicting severe malaria. Multivariate logistic regression showed that serum sodium < 131 mmol/L was independently associated with severe falciparum malaria (odds ratio 10.4, 95% confidence interval 3.1-34.9). In patients with hyponatraemia, hypovolaemia did not appear to play a significant role in the development of hyponatraemia when prerenal azotaemia and haematocrit were considered as surrogate markers for hypovolaemia.

Conclusions

Hyponatraemia is common in imported malaria and is associated with severe falciparum malaria. From a clinical point of view, the predictive power of hyponatraemia for severe malaria is limited. The precise pathophysiological mechanisms of hyponatraemia in malaria require further study.
Plasmodium falciparum proteome changes in response to doxycycline treatment
Authors: Briolant Sébastien , Almeras Lionel , Belghazi Maya , Boucomont-Chapeaublanc Elodie , Wurtz Nathalie , Fontaine Albin , Granjeaud Samuel , Fusaï Thierry , Rogier Christophe , Pradines Bruno
Published: May 2010

Background

The emergence of Plasmodium falciparum resistance to most anti-malarial compounds has highlighted the urgency to develop new drugs and to clarify the mechanisms of anti-malarial drugs currently used. Among them, doxycycline is used alone for malaria chemoprophylaxis or in combination with quinine or artemisinin derivatives for malaria treatment. The molecular mechanisms of doxycycline action in P. falciparum have not yet been clearly defined, particularly at the protein level.

Methods

A proteomic approach was used to analyse protein expression changes in the schizont stage of the malarial parasite P. falciparum following doxycycline treatment. A comparison of protein expression between treated and untreated protein samples was performed using two complementary proteomic approaches: two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and isobaric tagging reagents for relative and absolute quantification (iTRAQ).

Results

After doxycycline treatment, 32 and 40 P. falciparum proteins were found to have significantly deregulated expression levels by 2D-DIGE and iTRAQ methods, respectively. Although some of these proteins have been already described as being deregulated by other drug treatments, numerous changes in protein levels seem to be specific to doxycycline treatment, which could perturb apicoplast metabolism. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to confirm this hypothesis.

Conclusions

In this study, a specific response to doxycycline treatment was distinguished and seems to involve mitochondrion and apicoplast organelles. These data provide a starting point for the elucidation of drug targets and the discovery of mechanisms of resistance to anti-malarial compounds.
Identification of Siglec-9 as the receptor for MUC16 on human NK cells, B cells, and monocytes
Authors: Belisle Jennifer A , Horibata Sachi , Jennifer Gubbels AA , Petrie Sarah , Kapur Arvinder , André Sabine , Gabius Hans-Joachim , Rancourt Claudine , Connor Joseph , Paulson James C , Patankar Manish S
Published: May 2010

Background

MUC16 is a cell surface mucin expressed at high levels by epithelial ovarian tumors. Following proteolytic cleavage, cell surface MUC16 (csMUC16) is shed in the extracellular milieu and is detected in the serum of cancer patients as the tumor marker CA125. csMUC16 acts as an adhesion molecule and facilitates peritoneal metastasis of ovarian tumors. Both sMUC16 and csMUC16 also protect cancer cells from cytotoxic responses of natural killer (NK) cells. In a previous study we demonstrated that sMUC16 binds to specific subset of NK cells. Here, we identify the csMUC16/sMUC16 binding partner expressed on immune cells.

Results

Analysis of immune cells from the peripheral blood and peritoneal fluid of ovarian cancer patients indicates that in addition to NK cells, sMUC16 also binds to B cells and monocytes isolated from the peripheral blood and peritoneal fluid. I-type lectin, Siglec-9, is identified as the sMUC16 receptor on these immune cells. Siglec-9 is expressed on approximately 30-40% of CD16pos/CD56dimNK cells, 20-30% of B cells and >95% of monocytes. sMUC16 binds to the majority of the Siglec-9posNK cells, B cells and monocytes. sMUC16 is released from the immune cells following neuraminidase treatment. Siglec-9 transfected Jurkat cells and monocytes isolated from healthy donors bind to ovarian tumor cells via Siglec-9-csMUC16 interaction.

Conclusions

Recent studies indicate that csMUC16 can act as an anti-adhesive agent that blocks tumor-immune cell interactions. Our results demonstrate that similar to other mucins, csMUC16 can also facilitate cell adhesion by interacting with a suitable binding partner such as mesothelin or Siglec-9. Siglec-9 is an inhibitory receptor that attenuates T cell and NK cell function. sMUC16/csMUC16-Siglec-9 binding likely mediates inhibition of anti-tumor immune responses.
Transcriptional responses in the adaptation to ischaemia-reperfusion injury: a study of the effect of ischaemic preconditioning in total knee arthroplasty patients
Authors: Murphy Terence , Walsh Pauline M , Doran Peter P , Mulhall Kevin J
Published: May 2010

Background

Ischaemic preconditioning (IPC) has emerged as a method of reducing ischaemia-reperfusion injury. However, the complex mechanism through which IPC elicits this protection is not fully understood. The aim of this study was to investigate the genomic response induced by IPC in muscle biopsies taken from the operative leg of total knee arthroplasty patients in order to gain insight into the IPC mechanism.

Methods

Twenty patients, undergoing primary total knee arthroplasty, were randomly assigned to IPC (n = 10) and control (n = 10) groups. Patients in the IPC group received ischaemic preconditioning immediately prior to surgery. IPC was induced by three five-minute cycles of tourniquet insufflation interrupted by five-minute cycles of reperfusion. A muscle biopsy was taken from the operative knee of control and IPC-treated patients at the onset of surgery and, again, at one hour into surgery. The gene expression profile of muscle biopsies was determined using the Affymetrix Human U113 2.0 microarray system and validated using real-time polymerase chain reaction (RT-PCR). Measurements of C-reactive protein (CRP), erythrocyte sedimentation (ESR), white cell count (WCC), cytokines and haemoglobin were also made pre- and post-operatively.

Results

Microarray analysis revealed a significant increase in the expression of important oxidative stress defence genes, immediate early response genes and mitochondrial genes. Upregulation of pro-survival genes was also observed and correlated with a downregulation of pro-apoptotic gene expression. CRP, ESR, WCC, cytokine and haemoglobin levels were not significantly different between control and IPC patients.

Conclusions

The findings of this study suggest that IPC of the lower limb in total knee arthroplasty patients induces a protective genomic response, which results in increased expression of immediate early response genes, oxidative stress defence genes and pro-survival genes. These findings indicate that ischaemic preconditioning may be of potential benefit in knee arthroplasty and other musculoskeletal conditions.
Nonimmunoglobulin E-Mediated Immune Reactions to Foods
Authors: Spergel Jonathan M
Published: May 2010

Adverse food reactions are abnormal responses to ingested foods. Reactions vary from immunologic to nonimmunologic immune reactions and can be either immunoglobulin E (IgE) mediated or non-IgE mediated. Food-induced IgE-mediated reactions range from localized urticaria to anaphylaxis and have been well studied. However, in comparison, there has been significantly less research into non-IgE-mediated food reactions. Non-IgE-mediated reactions can cause respiratory, gastrointestinal, and cutaneous symptoms. The most recent evidence suggests that these reactions are probably T-cell mediated as evidenced in lymphocyte proliferation assays. This review will explore the symptoms and testing methods of the most common non-IgE-mediated reactions.
Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase
Authors: Emirandetti Amanda , Simões Gustavo F , Zanon Renata G , Oliveira Alexandre LR
Published: May 2010

Background

Astrocytes play a major role in preserving and restoring structural and physiological integrity following injury to the nervous system. After peripheral axotomy, reactive gliosis propagates within adjacent spinal segments, influenced by the local synthesis of nitric oxide (NO). The present work investigated the importance of inducible nitric oxide synthase (iNOS) activity in acute and late glial responses after injury and in major histocompatibility complex class I (MHC I) expression and synaptic plasticity of inputs to lesioned alpha motoneurons.

Methods

In vivo analyses were carried out using C57BL/6J-iNOS knockout (iNOS-/-) and C57BL/6J mice. Glial response after axotomy, glial MHC I expression, and the effects of axotomy on synaptic contacts were measured using immunohistochemistry and transmission electron microscopy. For this purpose, 2-month-old animals were sacrificed and fixed one or two weeks after unilateral sciatic nerve transection, and spinal cord sections were incubated with antibodies against classical MHC I, GFAP (glial fibrillary acidic protein - an astroglial marker), Iba-1 (an ionized calcium binding adaptor protein and a microglial marker) or synaptophysin (a presynaptic terminal marker). Western blotting analysis of MHC I and nNOS expression one week after lesion were also performed. The data were analyzed using a two-tailed Student's t test for parametric data or a two-tailed Mann-Whitney U test for nonparametric data.

Results

A statistical difference was shown with respect to astrogliosis between strains at the different time points studied. Also, MHC I expression by iNOS-/- microglial cells did not increase at one or two weeks after unilateral axotomy. There was a difference in synaptophysin expression reflecting synaptic elimination, in which iNOS-/- mice displayed a decreased number of the inputs to alpha motoneurons, in comparison to that of C57BL/6J.

Conclusion

The findings herein indicate that iNOS isoform activity influences MHC I expression by microglial cells one and two weeks after axotomy. This finding was associated with differences in astrogliosis, number of presynaptic terminals and synaptic covering of alpha motoneurons after lesioning in the mutant mice.
Pelvic skeletal metastasis of hepatocellular carcinoma with sarcomatous change: a case report
Authors: Chen Chih-Yu , Hsueh Yong-Te , Lan Tsung-Yu , Lin Wei-Hsin , Wu Karl , Yang Rong-Sen
Published: May 2010

Sarcomatoid hepatocellular carcinoma (HCC) is a very rare histologic variant of HCC. The characteristic of skeletal metastatic sarcomatoid hepatocellular carcinoma has never been reported. We reported a patient with sarcomatoid hepatocellular carcinoma pelvic metastasis who presented with huge pelvic metastasis that had relatively small osteolytic lesion centrally located accompanied by huge bipeduncular invasive expansile lesions into surrounding soft tissue. The lesion showed almost non-isotope uptake in 99mTc-methylene diphosphonate bone scintigraphy study. He underwent radiotherapy and tumor excision but the tumor rapidly recurred. In addition, serum α-fetoprotein level was never elevated beyond normal limit (< 20 ng/mL) through the whole course of treatment. We considered sarcomatoid hepatocellular carcinoma bone metastasis a highly aggressive lesion with unusual metastatic pattern. Surgical treatment with adequate safe margin in such a huge tumor with hypervascularity and extensive invasion in the pelvis was difficult; and radiotherapy maybe refractory regarding the sarcomatous nature. Therefore, debulking operation with local symptoms control may provide a better quality of life. And the clinical course suggests sarcomatoid hepatocellular carcinoma is derived from the transition of an ordinary hepatocellular carcinoma.
Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma
Authors: Hsieh Chen-Hsi , Liu Chia-Yuan , Shueng Pei-Wei , Chong Ngot-Swan , Chen Chih-Jen , Chen Ming-Jen , Lin Ching-Chung , Wang Tsang-En , Lin Shee-Chan , Tai Hung-Chi , Tien Hui-Ju , Chen Kuo-Hsin , Wang Li-Ying , Hsieh Yen-Ping , Huang David YC , Chen Yu-Jen
Published: May 2010

Background

To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT).

Methods

Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram.

Results

HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively.

Conclusion

Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.
Baseline cerebral oximetry values in cardiac and vascular surgery patients: a prospective observational study
Authors: Baikoussis Nikolaos G , Karanikolas Menelaos , Siminelakis Stavros , Matsagas Miltiadis , Papadopoulos Georgios
Published: May 2010

Aim

This study was conducted to evaluate baseline INVOS values and identify factors influencing preoperative baseline INVOS values in carotid endarterectomy and cardiac surgery patients.

Methods

This is a prospective observational study on 157 patients (100 cardiac surgery patients, 57 carotid endarterectomy patients). Data were collected on factors potentially related to baseline INVOS values. Data were analyzed with student's t-test, Chi-square, Pearson's correlation or Linear Regression as appropriate.

Results

100 cardiac surgery patients and 57 carotid surgery patients enrolled. Compared to cardiac surgery, carotid endarterectomy patients were older (71.05 ± 8.69 vs. 65.72 ± 11.04, P < 0.001), with higher baseline INVOS (P < 0.007) and greater stroke frequency (P < 0.002). Diabetes and high cholesterol were more common in cardiac surgery patients. Right side INVOS values were strongly correlated with left-side values in carotid (r = 0.772, P < 0.0001) and cardiac surgery patients (r = 0.697, P < 0.0001). Diabetes and high cholesterol were associated with significantly (P < 0.001) lower INVOS and smoking was associated with higher INVOS values in carotid, but not in cardiac surgery patients. Age, sex, CVA history, Hypertension, CAD, Asthma, carotid stenosis side and surgery side were not related to INVOS. Multivariate analysis showed that diabetes is strongly associated with lower baseline INVOS values bilaterally (P < 0.001) and explained 36.4% of observed baseline INVOS variability in carotid (but not cardiac) surgery.

Conclusion

Compared to cardiac surgery, carotid endarterectomy patients are older, with higher baseline INVOS values and greater stroke frequency. Diabetes and high cholesterol are associated with lower baseline INVOS values in carotid surgery. Right and left side INVOS values are strongly correlated in both patient groups.
Set-base dynamical parameter estimation and model invalidation for biochemical reaction networks
Authors: Rumschinski Philipp , Borchers Steffen , Bosio Sandro , Weismantel Robert , Findeisen Rolf
Published: May 2010

Background

Mathematical modeling and analysis have become, for the study of biological and cellular processes, an important complement to experimental research. However, the structural and quantitative knowledge available for such processes is frequently limited, and measurements are often subject to inherent and possibly large uncertainties. This results in competing model hypotheses, whose kinetic parameters may not be experimentally determinable. Discriminating among these alternatives and estimating their kinetic parameters is crucial to improve the understanding of the considered process, and to benefit from the analytical tools at hand.

Results

In this work we present a set-based framework that allows to discriminate between competing model hypotheses and to provide guaranteed outer estimates on the model parameters that are consistent with the (possibly sparse and uncertain) experimental measurements. This is obtained by means of exact proofs of model invalidity that exploit the polynomial/rational structure of biochemical reaction networks, and by making use of an efficient strategy to balance solution accuracy and computational effort.

Conclusions

The practicability of our approach is illustrated with two case studies. The first study shows that our approach allows to conclusively rule out wrong model hypotheses. The second study focuses on parameter estimation, and shows that the proposed method allows to evaluate the global influence of measurement sparsity, uncertainty, and prior knowledge on the parameter estimates. This can help in designing further experiments leading to improved parameter estimates.
Unusual presentation of cactus spines in the flank of an elderly man: a case report
Authors: Suárez Andrea , Freeman Scott , Puls Lauren , Dellavalle Robert
Published: May 2010

Introduction

Splinters and spines of plant matter are common foreign bodies in skin wounds of the extremities, and often present embedded in the dermis or subcutaneous tissue. Vegetative foreign bodies are highly inflammatory and, if not completely removed, can cause infection, toxic reactions, or granuloma formation. Older patients are at increased risk for infection from untreated plant foreign bodies. The most common error in plant splinter and spine management is failure to detect their presence.

Case presentation

Here we report a case of cactus spines in an 84-year-old Caucasian man presenting on the right flank as multiple, red papules with spiny extensions. This presentation was unusual both in location and the spinous character of the lesions, and only after punch biopsy analysis was a diagnosis of cactus matter spines made.

Conclusions

Our patient presented with an unusual case of cactus spines that required histopathology for identification. Skin lesions with neglected foreign bodies are a common cause of malpractice claims. If not removed, foreign bodies of the skin, particularly in elderly individuals, can result in inflammatory and infectious sequela. This report underscores the importance of thoroughly evaluating penetrating skin lesions for the presence of foreign bodies, such as splinters and spines.
A positive feedback-based gene circuit to increase the production of a membrane protein
Authors: Bansal Karan , Yang Ke , Nistala Goutam J , Gennis Robert B , Bhalerao Kaustubh D
Published: May 2010

Background

Membrane proteins are an important class of proteins, playing a key role in many biological processes, and are a promising target in pharmaceutical development. However, membrane proteins are often difficult to produce in large quantities for the purpose of crystallographic or biochemical analyses.

Results

In this paper, we demonstrate that synthetic gene circuits designed specifically to overexpress certain genes can be applied to manipulate the expression kinetics of a model membrane protein, cytochrome bd quinol oxidase in E. coli, resulting in increased expression rates. The synthetic circuit involved is an engineered, autoinducer-independent variant of the lux operon activator LuxR from V. fischeri in an autoregulatory, positive feedback configuration.

Conclusions

Our proof-of-concept experiments indicate a statistically significant increase in the rate of production of the bd oxidase membrane protein. Synthetic gene networks provide a feasible solution for the problem of membrane protein production.
Cellulose crystallinity index: measurement techniques and their impact on interpreting cellulase performance
Authors: Park Sunkyu , Baker John O , Himmel Michael E , Parilla Philip A , Johnson David K
Published: May 2010

Although measurements of crystallinity index (CI) have a long history, it has been found that CI varies significantly depending on the choice of measurement method. In this study, four different techniques incorporating X-ray diffraction and solid-state 13C nuclear magnetic resonance (NMR) were compared using eight different cellulose preparations. We found that the simplest method, which is also the most widely used, and which involves measurement of just two heights in the X-ray diffractogram, produced significantly higher crystallinity values than did the other methods. Data in the literature for the cellulose preparation used (Avicel PH-101) support this observation. We believe that the alternative X-ray diffraction (XRD) and NMR methods presented here, which consider the contributions from amorphous and crystalline cellulose to the entire XRD and NMR spectra, provide a more accurate measure of the crystallinity of cellulose. Although celluloses having a high amorphous content are usually more easily digested by enzymes, it is unclear, based on studies published in the literature, whether CI actually provides a clear indication of the digestibility of a cellulose sample. Cellulose accessibility should be affected by crystallinity, but is also likely to be affected by several other parameters, such as lignin/hemicellulose contents and distribution, porosity, and particle size. Given the methodological dependency of cellulose CI values and the complex nature of cellulase interactions with amorphous and crystalline celluloses, we caution against trying to correlate relatively small changes in CI with changes in cellulose digestibility. In addition, the prediction of cellulase performance based on low levels of cellulose conversion may not include sufficient digestion of the crystalline component to be meaningful.
Dynamic cross-talk analysis among TNF-R, TLR-4 and IL-1R signalings in TNFα-induced inflammatory responses
Authors: Yang Shih-Kuang , Wang Yu-Chao , Chao Chun-Cheih , Chuang Yung-Jen , Lan Chung-Yu , Chen Bor-Sen
Published: May 2010

Background

Development in systems biology research has accelerated in recent years, and the reconstructions for molecular networks can provide a global view to enable in-depth investigation on numerous system properties in biology. However, we still lack a systematic approach to reconstruct the dynamic protein-protein association networks at different time stages from high-throughput data to further analyze the possible cross-talks among different signaling/regulatory pathways.

Methods

In this study we integrated protein-protein interactions from different databases to construct the rough protein-protein association networks (PPANs) during TNFα-induced inflammation. Next, the gene expression profiles of TNFα-induced HUVEC and a stochastic dynamic model were used to rebuild the significant PPANs at different time stages, reflecting the development and progression of endothelium inflammatory responses. A new cross-talk ranking method was used to evaluate the potential core elements in the related signaling pathways of toll-like receptor 4 (TLR-4) as well as receptors for tumor necrosis factor (TNF-R) and interleukin-1 (IL-1R).

Results

The highly ranked cross-talks which are functionally relevant to the TNFα pathway were identified. A bow-tie structure was extracted from these cross-talk pathways, suggesting the robustness of network structure, the coordination of signal transduction and feedback control for efficient inflammatory responses to different stimuli. Further, several characteristics of signal transduction and feedback control were analyzed.

Conclusions

A systematic approach based on a stochastic dynamic model is proposed to generate insight into the underlying defense mechanisms of inflammation via the construction of corresponding signaling networks upon specific stimuli. In addition, this systematic approach can be applied to other signaling networks under different conditions in different species. The algorithm and method proposed in this study could expedite prospective systems biology research when better experimental techniques for protein expression detection and microarray data with multiple sampling points become available in the future.
Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients
Authors: Zhang Guan-Zhong , Jiao Shun-Chang , Meng Zhao-Ting
Published: May 2010

Background

The objective of this study was to evaluate the efficacy and safety of pemetrexed plus cisplatin/carboplatin in locally advanced or metastatic non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy.

Methods

Fifty-three locally advanced or metastatic non-small cell lung cancer patients previously treated with platinum-based chemotherapy received pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin area under the curve (AUC) 5 every 21 days, with dexamethasone, folic acid and vitamin B12 being administered.

Results

Median age was 52 years. Eastern Cooperative Oncology Group (ECOG) performance status was 0-2. Thirty-eight patients had stage IV tumors. Thirty-seven patients had adenocarcinoma (including 6 alveolar carcinoma patients), and fourteen patients had squamous cell carcinoma. Thirty-four patients were treated in second line, 15 in third line, and 4 in fourth line. Seven patients (13.2%) showed partial response; Thirty-six (67.9%) had stable disease. The median progression free survival time was 6.0 months and the median overall survival time was 10.0 months. The 1-year survival rate was 40.9%. Five (9.4%) and four (7.5%) patients experienced grade 3 or 4 leukopenia and thrombocytopenia, respectively. Nonhematological toxicities included grade 3 nausea/vomiting in 1 patient (1.9%), grade 3 rash in 1 patient, grade 4 diarrhea in 1 patient (1.9%) and grade 4 creatinine increase in 1 patient (1.9%).

Conclusion

Locally advanced or metastatic NSCLC patients previously treated with platinum-based chemotherapy could benefit from pemetrexed plus cisplatin/carboplatin chemotherapy with tolerable adverse events.
Methylation status of DDIT3 gene in Chronic Myeloid Leukemia
Authors: Wang Ya-li , Qian Jun , Lin Jiang , Yao Dong-ming , Qian Zhen , Zhu Zhao-hui , Li Jian-yong
Published: May 2010

Background

DNA-damage-inducible transcript 3 (DDIT3), a candidate tumor suppressor gene (TSG), has been found involved in the regulation of cellular growth and differentiation. The epigenetic changes of TSGs are recently recognized as an abnormal mechanism contributing to the development of chronic myeloid leukemia (CML). The aim of this study was to investigate the methylation status of DDIT3 gene in CML patients.

Methods

The methylation status of DDIT3 promoter was detected in the bone marrow mononuclear cells from 53 patients with CML using methylation-specific PCR (MSP). The expression levels of DDIT3 and bcr/abl transcript were determined by real-time quantitative PCR (RQ-PCR). Clinical data of these patients were collected and analyzed.

Results

The aberrant methylation of DDIT3 gene promoter was found in 35 of 53 (66%) CML cases. Correlation was not found between DDIT3 promoter hypermethylation and the age, sex, hemoglobin concentration, platelet counts, chromosomal abnormalities, bcr/abl transcript, and staging of CML patients (P > 0.05), but found between DDIT3 promoter hypermethylation and WBC counts of CML cases (R = 0.781, P < 0.001). The level of DDIT3 transcript in CML patients was significantly lower than that in controls (median 3.28 vs 19.69, P < 0.001), however, there was no difference in the level of DDIT3 transcript between methylation-positive CML cases (0.05-65.32, median 2.13) and methylation- negative CML cases (0.12-126.04, median 3.92) (P > 0.05).

Conclusion

Our results demonstrate that aberrant methylation of DDIT3 occurs in CML frequently.
Association between occupation and knee and hip replacement due to osteoarthritis: a case-control study
Authors: Franklin Jonas , Ingvarsson Thorvaldur , Englund Martin , Lohmander Stefan
Published: May 2010

Introduction

The objective of this study was to examine the association between occupation and osteoarthritis (OA) leading to total knee (TKR) or hip (THR) joint replacement.

Methods

The following is the case-control study design. All patients still living in Iceland who had had a TKR or THR due to OA as of the end of 2002 were invited to participate. First degree relatives of participating patients served as controls. N = 1,408 cases (832 women) and n = 1,082 controls (592 women), 60 years or older and who had adequately answered a questionnaire were analyzed. Occupations were classified according to international standards. Inheritance of occupations was calculated by using the Icelandic Genealogy Database.

Results

The age adjusted odds ratio (OR) for male farmers getting a TKR due to OA was 5.1 (95% confidence interval (CI) 2.1 to 12.4) and for a male farmer getting a THR due to OA the OR was 3.6 (95% CI 2.1 to 6.2). The OR for a fisherman getting a TKR was 3.3 (95% CI 1.3 to 8.4). No other occupations showed increased risk for men. For women there was no increased risk for any occupation. Farming and fishing were also the occupations that showed the greatest degree of inheritance.

Conclusions

These results support an association in males between occupations with heavy physical load and both TKR and THR for OA.