bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cisplatin preparation error; patient management and morbidity
Authors: Vila-Torres E. , Albert-Marí A. , Almenar-Cubells D. , Jiménez-Torres NV 
Published: March 2009

Introduction. Antineoplastic drug therapy errors represent a high iatrogenic potential due to antineoplastic drugs narrow therapeutic ranges and the complexity of chemotherapy regimens that may increase the risk of morbidity and mortality for oncology patients. Setting. We report a 57-year-old man with head and neck cancer who mistakenly received 180 mg/ m2 of cisplatin overdose despite the safety measures and validations carried out during preparation. The patient developed moderate nausea and vomiting, acute renal failure, hearing difficulty (tinnitus), and severe myelodepression. Patient management. Prophylactic and symptomatic treatments were applied in order to prevent and correct toxicity during the 9 days stay at hospital. Result. He recovered with mild tinnitus and mild renal impairment as the only sequelae. This case presents a hospital stay and treatment quite different to others used to reverse all cisplatin overdose toxicity and it shows the benefits of prompt management.
Pharmacokinetics of a granisetron transdermal system for the treatment of chemotherapy-induced nausea and vomiting
Authors: Howell Julian , Smeets Jean , Drenth Henk-Jan , Gill David 
Published: March 2009

Objective. To determine the pharmacokinetic (PK) profile of granisetron transdermal formulation and examine its possible relationship with age, gender, and renal function. Methods. This article describes a Phase I PK study and a post hoc pooled population PK analysis. The Phase I study was a randomized, cross-over study that assessed PK parameters of three granisetron patch sizes and oral granisetron. The pooled population PK analysis included data from three trials in healthy subjects (n = 48) and from Phase II and III studies in patients with cancer (n = 793). The population PK model was used to investigate granisetron exposure and its possible relationship with age, gender, and renal function. Results. Following oral dosing, plasma granisetron concentration was quantifiable at 1 h, and maximal mean concentration (4.7 ng/mL) was reached 2 h after administration. With transdermal application, maximal concentration was reached 48 h post-application; t1/2 was 36 h. With oral dosing, overall exposure after 5 days was 306 ng/mL·h, and Cavg 2.6 ng/mL. This corresponded to an AUC0—∞ for the 52 cm2 patch of 420 ng/mL·h and Cavg 2.2 ng/mL over 6 days. Clearance was not affected by age, gender, weight, or renal function. Conclusion. The 52 cm 2 granisetron patch achieves a similar exposure to that of a 2 mg oral dose and provides continuous delivery of granisetron over 6 days. The patch may have utility in treating chemotherapy-induced nausea and vomiting where prolonged drug delivery is advantageous. No dose adjustments would be needed based on age or renal function.
Zebrafish mutants in the von Hippel-Lindau tumor suppressor display a hypoxic response and recapitulate key aspects of Chuvash polycythemia
Authors: van Rooijen Ellen , Voest Emile E. , Logister Ive , Korving Jeroen , Schwerte Thorsten , Schulte-Merker Stefan , Giles Rachel H. , van Eeden Fredericus J. 
Published: March 2009

AbstractWe have generated 2 zebrafish lines carrying inactivating germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene ortholog vhl. Mutant embryos display a general systemic hypoxic response, including the up-regulation of hypoxia-induced genes by 1 day after fertilization and a severe hyperventilation and cardiophysiologic response. The vhl mutants develop polycythemia with concomitantly increased epo/epor mRNA levels and erythropoietin signaling. In situ hybridizations reveal global up-regulation of both red and white hematopoietic lineages. Hematopoietic tissues are highly proliferative, with enlarged populations of c-myb+ hematopoietic stem cells and circulating erythroid precursors. Chemical activation of hypoxia-inducible factor signaling recapitulated aspects of the vhl−/− phenotype. Furthermore, microarray expression analysis confirms the hypoxic response and hematopoietic phenotype observed in vhl−/− embryos. We conclude that VHL participates in regulating hematopoiesis and erythroid differentiation. Injections with human VHLp30 and R200W mutant mRNA demonstrate functional conservation of VHL between mammals and zebrafish at the amino acid level, indicating that vhl mutants are a powerful new tool to study genotype-phenotype correlations in human disease. Zebrafish vhl mutants are the first congenital embryonic viable systemic vertebrate animal model for VHL, representing the most accurate model for VHL-associated polycythemia to date. They will contribute to our understanding of hypoxic signaling, hematopoiesis, and VHL-associated disease progression.
Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity
Authors: Morrow Matthew P. , Pankhong Panyupa , Laddy Dominick J. , Schoenly Kimberly A. , Yan Jian , Cisper Neil , Weiner David B. 
Published: March 2009

AbstractImproving the potency of immune responses is paramount among issues concerning vaccines against deadly pathogens. IL-28B belongs to the newly described interferon lambda (IFNλ) family of cytokines, and has not yet been assessed for its potential ability to influence adaptive immune responses or act as a vaccine adjuvant. We compared the ability of plasmid-encoded IL-28B to boost immune responses to a multiclade consensus HIV Gag plasmid during DNA vaccination with that of IL-12. We show here that IL-28B, like IL-12, is capable of robustly enhancing adaptive immunity. Moreover, we describe for the first time how IL-28B reduces regulatory T-cell populations during DNA vaccination, whereas IL-12 increases this cellular subset. We also show that IL-28B, unlike IL-12, is able to increase the percentage of splenic CD8+ T cells in vaccinated animals, and that these cells are more granular and have higher antigen-specific cytolytic degranulation compared with cells taken from animals that received IL-12 as an adjuvant. Lastly, we report that IL-28B can induce 100% protection from mortality after a lethal influenza challenge. These data suggest that IL-28B is a strong candidate for further studies of vaccine or immunotherapy protocols.
New scoring schema for finding motifs in DNA Sequences
Authors: Zare-Mirakabad Fatemeh , Ahrabian Hayedeh , Sadeghi Mehdei , Nowzari-Dalini Abbas , Goliaei Bahram 
Published: March 2009

Abstract

Background
Pattern discovery in DNA sequences is one of the most fundamental problems in molecular biology with important applications in finding regulatory signals and transcription factor binding sites. An important task in this problem is to search (or predict) known binding sites in a new DNA sequence. For this reason, all subsequences of the given DNA sequence are scored based on an scoring function and the prediction is done by selecting the best score. By assuming no dependency between binding site base positions, most of the available tools for known binding site prediction are designed. Recently Tomovic and Oakeley investigated the statistical basis for either a claim of dependence or independence, to determine whether such a claim is generally true, and they presented a scoring function for binding site prediction based on the dependency between binding site base positions. Our primary objective is to investigate the scoring functions which can be used in known binding site prediction based on the assumption of dependency or independency in binding site base positions.

Results
We propose a new scoring function based on the dependency between all positions in biding site base positions. This scoring function uses joint information content and mutual information as a measure of dependency between positions in transcription factor binding site. Our method for modeling dependencies is simply an extension of position independency methods. We evaluate our new scoring function on the real data sets extracted from JASPAR and TRANSFAC data bases, and compare the obtained results with two other well known scoring functions.

Conclusion
The results demonstrate that the new approach improves known binding site discovery and show that the joint information content and mutual information provide a better and more general criterion to investigate the relationships between positions in the TFBS. Our scoring function is formulated by simple mathematical calculations. By implementing our method on several biological data sets, it can be induced that this method performs better than methods that do not consider dependencies.
Sugarcane genes associated with sucrose content
Authors: Papini-Terzi Flávia S , Rocha Flávia R , Vêncio Ricardo ZN , Felix Juliana M , Branco Diana S , Waclawovsky Alessandro J , Del Bem Luiz EV , Lembke Carolina G , Costa Maximiller DL , Nishiyama Milton Y , Vicentini Renato , Vincentz Michel GA , Ulian Eugênio C , Menossi Marcelo , Souza Glaucia M 
Published: March 2009

AbstractBackground -Sucrose content is a highly desirable trait in sugarcane as the worldwide demand for cost-effective biofuels surges. Sugarcane cultivars differ in their capacity to accumulate sucrose and breeding programs routinely perform crosses to identify genotypes able to produce more sucrose. Sucrose content in the mature internodes reach around 20% of the culms dry weight. Genotypes in the populations reflect their genetic program and may display contrasting growth, development, and physiology, all of which affect carbohydrate metabolism. Few studies have profiled gene expression related to sugarcane's sugar content. The identification of signal transduction components and transcription factors that might regulate sugar accumulation is highly desirable if we are to improve this characteristic of sugarcane plants.Results -We have evaluated thirty genotypes that have different Brix (sugar) levels and identified genes differentially expressed in internodes using cDNA microarrays. These genes were compared to existing gene expression data for sugarcane plants subjected to diverse stress and hormone treatments. The comparisons revealed a strong overlap between the drought and sucrose-content datasets and a limited overlap with ABA signaling. Genes associated with sucrose content were extensively validated by qRT-PCR, which highlighted several protein kinases and transcription factors that are likely to be regulators of sucrose accumulation. The data also indicate that aquaporins, as well as lignin biosynthesis and cell wall metabolism genes, are strongly related to sucrose accumulation. Moreover, sucrose-associated genes were shown to be directly responsive to short term sucrose stimuli, confirming their role in sugar-related pathways.Conclusion -Gene expression analysis of sugarcane populations contrasting for sucrose content indicated a possible overlap with drought and cell wall metabolism processes and suggested signaling and transcriptional regulators to be used as molecular markers in breeding programs. Transgenic research is necessary to further clarify the role of the genes and define targets useful for sugarcane improvement programs based on transgenic plants.
Quantitative real-time RT-PCR and chromogenic in situ hybridization: precise methods to detect HER-2 status in breast carcinoma
Authors: Rosa Fabíola E , Silveira Sara M , Silveira Cássia GT , Bérgamo Nádia A , Neto Francisco A Moraes , Domingues Maria AC , Soares Fernando A , Caldeira José RF , Rogatto Silvia R 
Published: March 2009

Abstract

Background

HER-2 gene testing has become an integral part of breast cancer patient diagnosis. The most commonly used assay in the clinical setting for evaluating HER-2 status is immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). These procedures permit correlation between HER-2 expression and morphological features. However, FISH signals are labile and fade over time, making post-revision of the tumor difficult. CISH (chromogenic in situ hybridization) is an alternative procedure, with certain advantages, although still limited as a diagnostic tool in breast carcinomas.

Methods
To elucidate the molecular profile of HER-2 status, mRNA and protein expression in 75 invasive breast carcinomas were analyzed by real time quantitative RT-PCR (qRT-PCR) and IHC, respectively. Amplifications were evaluated in 43 of these cases by CISH and in 11 by FISH.

Results
The concordance rate between IHC and qRT-PCR results was 78.9%, and 94.6% for qRT-PCR and CISH. Intratumoral heterogeneity of HER-2 status was identified in three cases by CISH. The results of the three procedures were compared and showed a concordance rate of 83.8%; higher discordances were observed in 0 or 1+ immunostaining cases, which showed high-level amplification (15.4%) and HER-2 transcript overexpression (20%). Moreover, 2+ immunostaining cases presented nonamplified status (50%) by CISH and HER-2 downexpression (38.5%) by qRT-PCR. In general, concordance occurred between qRT-PCR and CISH results. A high concordance was observed between CISH/qRT-PCR and FISH. Comparisons with clinicopathological data revealed a significant association between HER-2 downexpression and the involvement of less than four lymph nodes (P = 0.0350).

Conclusion
Based on these findings, qRT-PCR was more precise and reproducible than IHC. Furthermore, CISH was revealed as an alternative and useful procedure for investigating amplifications involving the HER-2 gene.
A microfluidic device to acquire high-magnification microphotographs of yeast cells
Authors: Ohnuki Shinsuke , Nogami Satoru , Ohya Yoshikazu 
Published: March 2009

AbstractBackgroundYeast cell morphology was investigated to reveal the molecular mechanisms of cell morphogenesis and to identify key factors of other processes such as cell cycle progression. We recently developed a semi-automatic image processing program called CalMorph, which allows us to quantitatively analyze yeast cell morphology with the 501 parameters as biological traits and uncover statistical relationships between cell morphological phenotypes and genotypes. However, the current semi-automatic method is not suitable for morphological analysis of large-scale yeast mutants for the reliable prediction of gene functions because of its low-throughput especially at the manual image-acquiring process.ResultsIn this study, we developed a microfluidic chip designed to acquire successive microscopic images of yeast cells suitable for CalMorph image analysis. With the microfluidic chip, the morphology of living cells and morphological changes that occur during the cell cycle were successfully characterized.ConclusionThe microfluidic chip enabled us to acquire the images faster than the conventional method. We speculate that the use of microfluidic chip is effective in acquiring images of large-scale for automated analysis of yeast strains.
In vivo and in vitro evaluation of an Acetobacter xylinum synthesized microbial cellulose membrane intended for guided tissue repair
Authors: Mendes Péricles Nóbrega , Rahal Sheila Canevese , Pereira-Junior Oduvaldo Câmara Marques , Fabris Viciany Erique , Lenharo Sara Lais Rahal , de Lima-Neto João Ferreira , da Cruz Landim-Alvarenga Fernanda 
Published: March 2009

Abstract

Background
Barrier materials as cellulose membranes are used for guided tissue repair. However, it is essential that the surrounding tissues accept the device. The present study histologically evaluated tissue reaction to a microbial cellulose membrane after subcutaneous implantation in mice. Furthermore, the interaction between mesenchymal stem cells and the biomaterial was studied in vitro to evaluate its ability to act as cellular scaffold for tissue engineering.

Methods
Twenty-five Swiss Albino mice were used. A 10 × 10 mm cellulose membrane obtained through biosynthesis using Acetobacter xylinum bacteria was implanted into the lumbar subcutaneous tissue of each mouse. The mice were euthanatized at seven, 15, 30, 60, and 90 days, and the membrane and surrounding tissues were collected and examined by histology.

Results
A mild inflammatory response without foreign body reaction was observed until 30 days post-surgery around the implanted membrane. Polarized microscopy revealed that the membrane remained intact at all evaluation points. Scanning electron microscopy of the cellulose membrane surface showed absence of pores. The in vitro evaluation of the interaction between cells and biomaterial was performed through viability staining analysis of the cells over the biomaterial, which showed that 95% of the mesenchymal stem cells aggregating to the cellulose membrane were alive and that 5% were necrotic. Scanning electron microscopy showed mesenchymal stem cells with normal morphology and attached to the cellulose membrane surface.

Conclusion
The microbial cellulose membrane evaluated was found to be nonresorbable, induced a mild inflammatory response and may prove useful as a scaffold for mesenchymal stem cells.
Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study
Authors: de Grauw Janny C , van de Lest Chris HA , van Weeren Paul René 
Published: March 2009

Abstract
Introduction
Inflammation is an important feature of many joint diseases, and levels of cartilage biomarkers measured in synovial fluid may be influenced by local inflammatory status. Little is known about the magnitude and time course of inflammation-induced changes in cartilage tissue turnover as measured in vivo by synovial fluid markers. We aimed to study temporal changes in concentrations of inflammatory mediators, matrix metalloproteinase activity and cartilage biomarkers over 1 week in joints with experimentally induced inflammation.

Methods
Localized inflammation was induced in the intercarpal joint of six horses by sterile injection of 0.5 ng lipopolysaccharide, and synovial fluid was collected at post-injection hours (PIH) 0, 8, 24 and 168. Concentrations of inflammatory mediators (prostaglandin E2, substance P, and bradykinin), general matrix metalloproteinase activity and markers of collagen II turnover (CPII and C2C) as well as aggrecan turnover (CS846 and glycosaminoglycans) were measured with appropriate assays. One-way analysis of variance on repeated measures was used to analyze differences in synovial fluid marker levels over time.

Results
Lipopolysaccharide-injection led to a sharp rise in prostaglandin E2 at PIH 8, while substance P, bradykinin and matrix metalloproteinase activity showed more sustained increases at PIH 8 and 24. Glycosaminoglycan release paralleled changes in the CS846 epitope, with an increase by PIH 8, a peak at PIH 24, and return to baseline by PIH 168. For type II collagen, a parallel time course between catabolic (C2C) and anabolic (CPII) markers was also observed, but the time course differed from that seen for proteoglycan markers: collagen II markers peaked later, at PIH 24, and were still elevated over baseline at PIH 168.

Conclusions
A primary intra-articular inflammatory insult, characterized by local release of peptide and lipid mediators and matrix metalloproteinase activation, can alter synovial fluid levels of proteoglycan biomarkers as early as 8 hours post-induction, and can lead to sustained rises in collagen II biomarkers during at least 1 week after onset.
Crystalloids versus colloids for goal-directed fluid therapy in major surgery
Authors: Hiltebrand Luzius B , Kimberger Oliver , Arnberger Michael , Brandt Sebastian , Kurz Andrea , Sigurdsson Gisli H 
Published: March 2009

Abstract
Introduction
Perioperative hypovolemia arises frequently and contributes to intestinal hypoperfusion and subsequent postoperative complications. Goal-directed fluid therapy might reduce these complications. The aim of this study was to compare the effects of goal-directed administration of crystalloids and colloids on the distribution of systemic, hepatosplanchnic, and microcirculatory (small intestine) blood flow after major abdominal surgery in a clinically relevant pig model.

Methods
Twenty-seven pigs were anesthetized and mechanically ventilated and underwent open laparotomy. They were randomly assigned to one of three treatment groups: the restricted Ringer lactate (R-RL) group (n = 9) received 3 mL/kg per hour of RL, the goal-directed RL (GD-RL) group (n = 9) received 3 mL/kg per hour of RL and intermittent boluses of 250 mL of RL, and the goal-directed colloid (GD-C) group (n = 9) received 3 mL/kg per hour of RL and boluses of 250 mL of 6% hydroxyethyl starch (130/0.4). The latter two groups received a bolus infusion when mixed venous oxygen saturation was below 60% ('lockout' time of 30 minutes). Regional blood flow was measured in the superior mesenteric artery and the celiac trunk. In the small bowel, microcirculatory blood flow was measured using laser Doppler flowmetry. Intestinal tissue oxygen tension was measured with intramural Clark-type electrodes.

Results
After 4 hours of treatment, arterial blood pressure, cardiac output, mesenteric artery flow, and mixed oxygen saturation were significantly higher in the GD-C and GD-RL groups than in the R-RL group. Microcirculatory flow in the intestinal mucosa increased by 50% in the GD-C group but remained unchanged in the other two groups. Likewise, tissue oxygen tension in the intestine increased by 30% in the GD-C group but remained unchanged in the GD-RL group and decreased by 18% in the R-RL group. Mesenteric venous glucose concentrations were higher and lactate levels were lower in the GD-C group compared with the two crystalloid groups.

Conclusions
Goal-directed colloid administration markedly increased microcirculatory blood flow in the small intestine and intestinal tissue oxygen tension after abdominal surgery. In contrast, goal-directed crystalloid and restricted crystalloid administrations had no such effects. Additionally, mesenteric venous glucose and lactate concentrations suggest that intestinal cellular substrate levels were higher in the colloid-treated than in the crystalloid-treated animals. These results support the notion that perioperative goal-directed therapy with colloids might be beneficial during major abdominal surgery.
Interferon-λs: the modulators of antivirus, antitumor, and immune responses
Authors: Li Mingcai , Liu Xiaojin , Zhou Yanchun , Su Shao Bo 
Published: March 2009

Abstract
Recent findings concerning the biology of IFN-λs and their pathophysiological roles in viral infection, cancer, and immune responses of the innate and adaptive arms are summarized.
IFN-λs, including IFN-λ1, IFN-λ2, and IFN-λ3, also known as IL-29, IL-28A, or IL-28B, are a newly described group of cytokines distantly related to the type I IFNs and IL-10 family members. The IFN-λR complex consists of a unique ligand-binding chain, IFN-λR1 (also designated IL-28Rα), and an accessory chain, IL-10R2, which is shared with receptors for IL-10-related cytokines. IFN-λs signal through the IFN-λR and activate pathways of JAK-STATs and MAPKs to induce antiviral, antiproliferative, antitumor, and immune responses. In this review, we summarize recent findings about the biology of IFN-λs and their pathophysiological roles in viral infection, cancer, and immune responses of the innate and adaptive arms.