bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitumor activity of mixed heat shock protein/peptide vaccine and cyclophosphamide plus interleukin-12 in mice sarcoma
Authors: Guo Quan-Yi , Yuan Mei , Peng Jiang , Cui Xue-Mei , Song Ge , Sui Xiang , Lu Shi-Bi 
Published: February 2011

Abstract

Background
The immune factors heat shock protein (HSP)/peptides (HSP/Ps) can induce both adaptive and innate immune responses. Treatment with HSP/Ps in cancer cell-bearing mice and cancer patients revealed antitumor immune activity. We aimed to develop immunotherapy strategies by vaccination with a mixture of HSP/Ps (mHSP/Ps, HSP60, HSP70, Gp96 and HSP110) enhanced with cyclophosphamide (CY) and interleukin-12 (IL-12).

Methods
We extracted mHSP/Ps from the mouse sarcoma cell line S180 using chromatography. The identity of proteins in this mHSP/Ps was assayed using SDS-PAGE and Western blot analysis with antibodies specific to various HSPs. BALB/C mice bearing S180 cells were vaccinated with mHSP/Ps ×3, then were injected intraperitoneally with low-dose CY and subcutaneously with IL-12, 100 μg/day, ×5. After vaccination, T lymphocytes in the peripheral blood were analyzed using FACScan and Cytotoxicity (CTL) was analyzed using lactate dehydrogenase assay. ELISPOT assay was used to evaluate interferon γ (IFN-γ), and immune cell infiltration in tumors was examined in the sections of tumor specimen.

Results
In mice vaccinated with enhanced vaccine (mHSP/Ps and CY plus IL-12), 80% showed tumor regression and long-term survival, and tumor growth inhibition rate was 82.3% (30 days), all controls died within 40 days. After vaccination, lymphocytes and polymorphonuclear leukocytes infiltrated into the tumors of treated animals, but no leukocytes infiltrated into the tumors of control mice. The proportions of natural killer cells, CD8+, and interferon-γ-secreting cells were all increased in the immune group, and tumor-specific cytotoxic T lymphocyte activity was increased.

Conclusions
In this mice tumor model, vaccination with mHSP/Ps combined with low-dose CY plus IL-12 induced an immunologic response and a marked antitumor response to autologous tumors. The regimen may be a promising therapeutic agent against tumors.
Liquid chromatography-tandem mass spectrometry method for the measurement of serum mevalonic acid: a novel marker of hydroxymethylglutaryl coenzyme A reductase inhibition by statins
Authors: Waldron Jenna , Webster Craig 
Published: February 2011

Background Mevalonic acid (MVA) is synthesized at an early and rate-limiting step in the biosynthesis of cholesterol by the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, and is a useful measure of statin efficacy or treatment. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the measurement of serum MVA has been developed. Methods Following the in vitro conversion of MVA to mevalonic acid lactone (MVAL) in the serum, MVAL and a deuterated internal standard were extracted using an online solid-phase extraction procedure. Chromatographic separation was achieved using a Luna PFP column (Phenomenex), with enhanced selectivity and improved resolution for polar compounds. A gradient system was used, with mobile phase comprising methanol and water (5 mmol/L ammonium formate buffer, pH 2.5). Analysis was performed using an API 5000 tandem mass spectrometer (Applied Biosystems) in positive electrospray ionization mode. Results The method showed excellent recoveries (98 ± 8%) and imprecision (intra-assay coefficient of variation of 2.2% [6.5 ng/mL] and 2.6% [10.5 ng/mL], and inter-assay coefficient of variation of 9% [10.5 ng/mL]). The assay provides a calibration range up to 50 ng/mL with a limit of detection at 0.1 ng/mL. Conclusion A simple, rapid and analytically specific method has been developed for the measurement of serum MVA, in the form of MVAL. The high analytical sensitivity of the method allows for accurate quantitation of MVAL in serum samples, both at the endogenous levels found in healthy individuals and in statin-treated patients where normal levels are expected to be greatly reduced through the inhibition of HMG-CoA reductase.
Evaluation of the interference due to haemoglobin, bilirubin and lipids on Immulite 2500 assays: a practical approach
Authors: Steen Gerard , Klerk Alex , Laan Kees van der , Eppens Elaine F 
Published: February 2011

Background Interfering substances such as haemoglobin, bilirubin and lipids in a sample may lead to wrong interpretation of immunoassay results by the clinician. In general, there has been minor attention to these interferences on immunoassays, whereas these effects on chemical assays are frequently described. Information about interferences by haemoglobin, bilirubin and lipids on the Siemens Immulite 2500 assays in the instructions for use is falling short. Methods Interferents in patient samples can be measured reliably in a semi-quantitative way on most chemistry analysers and can be expressed in haemolysis-, icterus- and lipaemia-indices. As the Immulite 2500 cannot perform such measurements, samples are normally analysed without testing for the presence of interferents. Therefore, a study was carried out to examine these interferences on 24 Immulite 2500 assays. Samples were spiked with increasing concentrations of either haemoglobin, bilirubin or lipids. The haemolysis-, icterus- and lipaemia-indices were measured on a Synchron DxC 800 analyser. Results Based on analytical imprecision and intraindividual biological variation of each analyte, cut-off indices above which clinically significant interference exists were determined. We found clinically significant interference due to haemoglobin on ferritin and folate, by bilirubin on oestradiol and testosterone and by lipids on testosterone. Conclusions Introducing cut-off indices prevents reporting of wrong Immulite 2500 results due to interference. Our results are applicable in laboratories using any chemistry analyser capable of reporting semi-quantitative concentrations of interferents.
A study of the effect of desensitization on hyperaesthesia in the hand and upper extremity after injury or surgery
Authors: Göransson Ingrid , Cederlund Ragnhild 
Published: February 2011

Introduction Hyperaesthesia is a common problem in hand rehabilitation. A desensitization programme has successfully been used in our occupational therapy department for patients with hyperaesthesia in the hand or upper extremity. Our objectives were to investigate self-perceived pain/discomfort at rest, with use or touch, size of sensitive skin area and occupational performance in daily occupations for patients with hyperaesthesia before and after a six-week desensitization programme. Methods Thirty-nine patients with pain/discomfort at or near scars from hand injury or surgery participated in the study. The patients were recruited consecutively to the study. They were instructed to massage the sensitive skin area three times a day with a piece of texture until numbness occurred (2–5 minutes). The textures were upgraded continuously. A study-specific questionnaire was developed including demographic data and questions concerning perceived pain/discomfort. Pain/discomfort was assessed with a visual analogue scale 0–100. The size of the sensitive skin area was assessed in mm2. Occupational performance was assessed with the Canadian Occupational Performance Measure. Results The results showed statistically significant improvements ( P ≤ 0.001) in all areas after six weeks with reduced pain/discomfort at rest and with use or touch, a decreased size of the sensitive skin area and a higher occupational performance in daily occupations. Discussion The results indicate the importance of paying attention to sensory disturbances during rehabilitation. The cost for such a programme is low. Further research is needed to confirm the results in a larger sample using a control group, and in comparison with spontaneous healing and other treatment modalities.
Evaluation of an evidence-based patient pathway for non-surgical and surgically managed metacarpal fractures
Authors: Midgley Robyn , Toemen Angela 
Published: February 2011

Introduction A review of current literature was used to develop an evidence-based pathway, managing surgical and non-surgical metacarpal fractures according to their anatomical location and fracture stability. The aim of this paper is to evaluate functional outcome, splint compliance, range of motion (ROM), residual pain, return to work and patient satisfaction following treatment based on the pathway. Method Fifty patients referred for surgical or non-surgical management of metacarpal fracture(s) were selected to participate in the clinical evaluation. Patient demographics, fracture site, management approach, type of splint, number of appointments attended and complications were recorded. A telephone questionnaire was used to evaluate patient satisfaction, compliance with splinting, ROM, pain, return to work and functional outcome. Recorded complications included infection, malunion, nonunion, rotational deformity and angulation deformity. Results Thirty-six patients were contactable 10–24 weeks post-injury. A total of 23 metacarpal neck/head, eight shaft and four base fractures were included. Ninety-four percent (34/36) of fractures were treated non-operatively. Patients were compliant with splinting in 17/36 (47%) cases. There were no reported complications. Seventy-two percent reported no pain at follow-up. All employed patients returned to work. Full ROM was reported in all cases. Full functional use of the hand was present in 92% of cases. Patients reported high satisfaction with the service (8/10) and required an average of three therapy appointments. Conclusion The metacarpal fracture evidence-based pathway was successful with 92% of patients returning to full function. The absence of complications emphasizes hand therapy's ability to efficiently and cost-effectively manage these fractures following referral. The pathway has been further refined as a result of the clinical evaluation, with alteration of the metacarpal shaft fracture splint, removal of repeat X-rays and reduction of splinting durations. It is recommended that the revised pathway is further evaluated.
Targeting BRAFV600E with PLX4720 Displays Potent Antimigratory and Anti-invasive Activity in Preclinical Models of Human Thyroid Cancer
Authors: Nucera Carmelo , Nehs Matthew A. , Nagarkatti Sushruta S. , Sadow Peter M. , Mekel Michal , Fischer Andrew H. , Lin Paul S. , Bollag Gideon E. , Lawler Jack , Hodin Richard A. , Parangi Sareh 
Published: February 2011

Abstract

Purpose.
B-RafV600E may play a role in the progression from papillary thyroid cancer to anaplastic thyroid cancer (ATC). We tested the effects of a highly selective B-RafV600E inhibitor, PLX4720, on proliferation, migration, and invasion both in human thyroid cancer cell lines (8505cB-RafV600E and TPC-1RET/PTC-1 and wild-type B-Raf) and in primary human normal thyroid (NT) follicular cells engineered with or without B-RafV600E.

Experimental Design.
Large-scale genotyping analysis by mass spectrometry was performed in order to analyze &gt;900 gene mutations. Cell proliferation and migration/invasion were performed upon PLX4720 treatment in 8505c, TPC-1, and NT cells. Orthotopic implantation of either 8505c or TPC-1 cells into the thyroid of severe combined immunodeficient mice was performed. Gene validations were performed by quantitative polymerase chain reaction and immunohistochemistry.

Results.
We found that PLX4720 reduced in vitro cell proliferation and migration and invasion of 8505c cells, causing early downregulation of genes involved in tumor progression. PLX4720-treated NT cells overexpressing B-RafV600E (heterozygous wild-type B-Raf/B-RafV600E) showed significantly lower cell proliferation, migration, and invasion. PLX4720 treatment did not block cell invasion in TPC-1 cells with wild-type B-Raf, which showed very low and delayed in vivo tumor growth. In vivo, PLX4720 treatment of 8505c orthotopic thyroid tumors inhibited tumor aggressiveness and significantly upregulated the thyroid differentiation markers thyroid transcription factor 1 and paired box gene 8.

Conclusions.
Here, we have shown that PLX4720 preferentially inhibits migration and invasion of B-RafV600E thyroid cancer cells and tumor aggressiveness. Normal thyroid cells were generated to be heterozygous for wild-type B-Raf/B-RafV600E, mimicking the condition found in most human thyroid cancers. PLX4720 was effective in reducing cell proliferation, migration, and invasion in this heterozygous model. PLX4720 therapy should be tested and considered for a phase I study for the treatment of patients with B-RafV600E ATC.
Neuronal Receptor Activity–Modifying Protein 1 Promotes Energy Expenditure in Mice
Authors: Zhang Zhongming , Liu Xuebo , Morgan Donald A. , Kuburas Adisa , Thedens Daniel R. , Russo Andrew F. , Rahmouni Kamal 
Published: February 2011

OBJECTIVE
Receptor activity–modifying proteins (RAMPs) 1, 2, and 3 are unusual accessory proteins that dictate the binding specificity of two G protein–coupled receptors involved in energy homeostasis: calcitonin gene–related peptide (CGRP) and amylin receptors. These proteins are expressed throughout the central nervous system (CNS), including in the brain regions involved in the regulation of energy homeostasis, but the significance of CNS RAMPs in the control of energy balance remains unknown.

RESEARCH DESIGN AND METHODS
To examine the functional significance of modulating neuronal RAMP1, we assessed the effect of overexpressing human RAMP1 (hRAMP1) in the CNS on body energy balance.

RESULTS
Nestin/hRAMP1 transgenic mice have a remarkably decreased body weight associated with reduced fat mass and circulating leptin levels. The transgenic mice exhibited higher energy expenditure as indicated by increased oxygen consumption, body temperature, and sympathetic tone subserving brown adipose tissue (BAT). Consistent with this, the nestin/hRAMP1 transgenic mice had elevated BAT mRNA levels of peroxisome proliferator–activated receptor γ coactivator 1α and uncoupling protein 1 and 3, and these changes can be reversed by chronic blockade of sympathetic nervous system signaling. Furthermore, metabolic response to amylin was enhanced in the nestin/hRAMP1 mice whereas the response to CGRP was blunted, possibly the result of higher expression of CGRP in the CNS.

CONCLUSIONS
These data demonstrate that CNS RAMP1 plays a pivotal role in the regulation of energy homeostasis by promoting energy expenditure.
Focal Adhesion Remodeling Is Crucial for Glucose-Stimulated Insulin Secretion and Involves Activation of Focal Adhesion Kinase and Paxillin
Authors: Rondas Dieter , Tomas Alejandra , Halban Philippe A. 
Published: February 2011

OBJECTIVE
Actin cytoskeleton remodeling is known to be involved in glucose-stimulated insulin secretion (GSIS). We have observed glucose-stimulated changes at the β-cell basal membrane similar to focal adhesion remodeling in cell migration. This led us to study the role of two key focal adhesion proteins, focal adhesion kinase (FAK) and paxillin, in GSIS.

RESEARCH DESIGN AND METHODS
All studies were performed using rat primary β-cells or isolated islets. Protein phosphorylation and subcellular localization were determined by Western blotting and confocal immunofluorescence, respectively. Insulin was measured by radioimmunoassay. Both siRNA and pharmacological approaches were used to assess the role of FAK and paxillin in glucose-stimulated focal adhesion remodeling and insulin secretion.

RESULTS
Glucose stimulation of β-cells in monolayer significantly increased phosphorylation of FAK and paxillin as well as cell surface area. This coincided with the appearance at the basal membrane of numerous shorter actin filopodial extensions, containing not only phosphorylated paxillin, FAK, and extracellular signal–related kinase 1/2 but also two SNARE proteins, synaptosomal-associated protein 25 and syntaxin 1, indicating involvement in exocytosis. SR7037 completely inhibited this sequence of events, indicating the requirement of increased cytosolic Ca2+. Furthermore, knockdown of paxillin significantly decreased GSIS, as did inhibition of glucose-induced FAK phosphorylation by compound Y15. Key findings were confirmed in β-cells within the natural setting of islets.

CONCLUSIONS
Glucose-stimulated remodeling of focal adhesions and phosphorylation of FAK and paxillin are involved in full development of GSIS, indicating a previously unknown role for focal adhesion remodeling in pancreatic β-cell function.
Endoplasmic Reticulum Stress Promotes LIPIN2-Dependent Hepatic Insulin Resistance
Authors: Ryu Dongryeol , Seo Woo-Young , Yoon Young-Sil , Kim Yo-Na , Kim Su Sung , Kim Hye-Jin , Park Tae-Sik , Choi Cheol Soo , Koo Seung-Hoi 
Published: February 2011

OBJECTIVE
Diet-induced obesity (DIO) is linked to peripheral insulin resistance—a major predicament in type 2 diabetes. This study aims to identify the molecular mechanism by which DIO-triggered endoplasmic reticulum (ER) stress promotes hepatic insulin resistance in mouse models.

RESEARCH DESIGN AND METHODS
C57BL/6 mice and primary hepatocytes were used to evaluate the role of LIPIN2 in ER stress-induced hepatic insulin resistance. Tunicamycin, thapsigargin, and lipopolysaccharide were used to invoke acute ER stress conditions. To promote chronic ER stress, mice were fed with a high-fat diet for 8–12 weeks. To verify the role of LIPIN2 in hepatic insulin signaling, adenoviruses expressing wild-type or mutant LIPIN2, and shRNA for LIPIN2 were used in animal studies. Plasma glucose, insulin levels as well as hepatic free fatty acids, diacylglycerol (DAG), and triacylglycerol were assessed. Additionally, glucose tolerance, insulin tolerance, and pyruvate tolerance tests were performed to evaluate the metabolic phenotype of these mice.

RESULTS
LIPIN2 expression was enhanced in mouse livers by acute ER stress–inducers or by high-fat feeding. Transcriptional activation of LIPIN2 by ER stress is mediated by activating transcription factor 4, as demonstrated by LIPIN2 promoter assays, Western blot analyses, and chromatin immunoprecipitation assays. Knockdown of hepatic LIPIN2 in DIO mice reduced fasting hyperglycemia and improved hepatic insulin signaling. Conversely, overexpression of LIPIN2 impaired hepatic insulin signaling in a phosphatidic acid phosphatase activity–dependent manner.

CONCLUSIONS
These results demonstrate that ER stress–induced LIPIN2 would contribute to the perturbation of hepatic insulin signaling via a DAG-protein kinase C ε–dependent manner in DIO mice.
Association Between Passive and Active Smoking and Incident Type 2 Diabetes in Women
Authors: Zhang Luxia , Curhan Gary C. , Hu Frank B. , Rimm Eric B. , Forman John P. 
Published: February 2011

OBJECTIVE
Accumulating evidence has identified a positive association between active smoking and the risk of diabetes, but previous studies had limited information on passive smoking or changes in smoking behaviors over time. This analysis examined the association between exposure to passive smoke, active smoking, and the risk of incident type 2 diabetes among women.

RESEARCH DESIGN AND METHODS
This is a prospective cohort study of 100,526 women in the Nurses’ Health Study who did not have prevalent diabetes in 1982, with follow-up for diabetes for 24 years.

RESULTS
We identified 5,392 incident cases of type 2 diabetes during 24 years of follow-up. Compared with nonsmokers with no exposure to passive smoke, there was an increased risk of diabetes among nonsmokers who were occasionally (relative risk [RR] 1.10 [95% CI 0.94–1.23]) or regularly (1.16 [1.00–1.35]) exposed to passive smoke. The risk of incident type 2 diabetes was increased by 28% (12–50) among all past smokers. The risk diminished as time since quitting increased but still was elevated even 20–29 years later (1.15 [1.00–1.32]). Current smokers had the highest risk of incident type 2 diabetes in a dose-dependent manner. Adjusted RRs increased from 1.39 (1.17–1.64) for 1–14 cigarettes per day to 1.98 (1.57–2.36) for ≥25 cigarettes per day compared with nonsmokers with no exposure to passive smoke.

CONCLUSIONS
Our study suggests that exposure to passive smoke and active smoking are positively and independently associated with the risk of type 2 diabetes.
A Learning Algorithm based on Primary School Teaching Wisdom
Authors: Philip Ninan Sajeeth 
Published: February 2011

AbstractA learning algorithm based on primary school teaching and learning is presented. The methodology is to continuously evaluate the performance of the network and to train it on the examples for which they repeatedly fail, until all the examples are correctly classified. Empirical analysis on UCI data show that the algorithm produces good training data and improves the generalization ability of the network on unseen data. The algorithm has interesting applications in data mining, model evaluations and rare objects discovery.
Motion Planning of a Snake-Like Robot Using an Optimized Harmonic Potential Field
Authors: Charifa Samer , Bikdash Marwan 
Published: February 2011

AbstractSnake-like robots have gained popularity in the last three decades for their ability to utilize several gaits in order to navigate through different terrains. They are analogous in morphology to snakes, tentacles, and elephant trunks. We propose a novel method of navigating a snake-like robot based on the Harmonic Field with Optimized Boundary Conditions (HFOBC) and a boundary following algorithm. We apply the HFOBC navigation function using a number of fictitious charges equally spaced on each link. These charges actively follow the potential field towards the target. Futhermore, a generalized mathematical model for an n-link snake-like robot based on Lagrange formulation has also been proposed in this paper.
Planning, implementing, and monitoring multiple‐species habitat conservation plans
Authors: Franklin Janet , Regan Helen M. , Hierl Lauren A. , Deutschman Douglas H. , Johnson Brenda S. , Winchell Clark S. 
Published: February 2011

•Premise of the study: Despite numerous recommendations for various aspects of the design and monitoring of habitat conservation plans, there remains a need to synthesize existing guidelines into a comprehensive scheme and apply it to real‐world conservation programs.•Methods: We review tools for systematic conservation planning and elements for designing and implementing ecological monitoring in an adaptive management context. We apply principles of monitoring design to the San Diego Multiple Species Conservation Program (MSCP) in California, USA—one of the first multispecies habitat conservation plans, located in a landscape where high biodiversity and urban development converge.•Key results: Tools for spatial conservation planning are aimed to conserve biodiversity, often in the context of a limited budget. In practice, these methods may not accommodate legislative mandates, budgetary uncertainties, and the range of implementation mechanisms available across consortia of stakeholders. Once a reserve is implemented, the question becomes whether it is effective at conserving biodiversity, and if not, what actions are required to make it effective. In monitoring plan development, status and threats should be used to prioritize species and communities that require management action to ensure their persistence. Conceptual models documenting the state of knowledge of the system should highlight the main drivers affecting status and trends of species or communities. Monitoring strategies require scientifically justified decisions based on sampling, response, and data design.•Conclusions: Because the framework illustrated here tackles multiple species, communities, and threats at the urban–wildland interface, it will have utility for ecosystem managers struggling to design monitoring programs.