bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload
Authors: Hankins Jane S. , Smeltzer Matthew P. , McCarville M. Beth , Aygun Banu , Hillenbrand Claudia M. , Ware Russell E. , Onciu Mihaela 
Published: March 2010

AbstractThe rate and pattern of iron deposition and accumulation are important determinants of liver damage in chronically transfused patients. To investigate iron distribution patterns at various tissue iron concentrations, effects of chelation on hepatic iron compartmentalization, and differences between patients with sickle cell disease (SCD) and thalassemia major (TM), we prospectively investigated hepatic histologic and biochemical findings in 44 patients with iron overload (35 SCD and 9 TM). The median hepatic iron content (HIC) in patients with TM and SCD was similar at 12.9 and 10.3 mg Fe/g dry weight, respectively (P = 0.73), but patients with SCD had significantly less hepatic fibrosis and inflammation (P < 0.05), less hepatic injury, and significantly less blood exposure. Patients with SCD had predominantly sinusoidal iron deposition, but hepatocyte iron deposition was observed even at low HIC. Chelated patients had more hepatocyte and portal tract iron than non‐chelated ones, but similar sinusoidal iron deposition. These data suggest that iron deposition in patients with SCD generally follows the traditional pattern of transfusional iron overload; however, parenchymal hepatocyte deposition also occurs early and chelation removes iron preferentially from the reticuloendothelium. Pathophysiological and genetic differences affecting iron deposition and accumulation in SCD and TM warrants further investigation (http://www.clinicaltrials.gov # NCT00675038).
BSc2118 is a novel proteasome inhibitor with activity against multiple myeloma
Authors: Sterz Jan , Jakob Christian , Kuckelkorn Ulrike , Heider Ulrike , Mieth Maren , Kleeberg Lorenz , Kaiser Martin , Kloetzel Peter‐M. , Sezer Orhan , Von Metzler Ivana 
Published: March 2010

AbstractObjectives:  The ubiquitin–proteasome system emerged as a new therapeutic target in cancer treatment. The purpose of this study was to elucidate the effects of the novel proteasome inhibitor BSc2118 on t(4;14) positive and negative multiple myeloma (MM) cells and normal peripheral blood mononuclear cells (PBMNC).Methods:  Human MM cell lines OPM‐2, RPMI‐8226, and U266 and primary MM cells from bone marrow aspirates were exposed to BSc2118. Cytotoxicity levels were evaluated using the MTT‐test. BSc2118‐induced apoptosis was analyzed by annexin‐V assay. Further methods used included proteasomal activity determination, cell cycle analysis, western blot, and transcription factor assays.Results:  In OPM‐2, RPMI‐8226, U266 cell lines and primary MM cells, BSc2118 caused dose‐dependent growth inhibitory effects. After 48 h, dose‐dependent apoptosis occurred both in cell lines and primary myeloma cells irrespective of t(4;14). A significant G2‐M cell cycle arrest occurred after 24 h. Furthermore, we observed a marked inhibition of intracellular proteasome activity, an increase in intracellular p21 levels, and an inhibition of NF‐κB activation. The toxicity against PBMNC remained low, suggesting a broad therapeutic range of this agent.Conclusion:  Taken together, BSc2118 shows significant antimyeloma activity and may be considered as a promising agent in cancer drug development.
Triose phosphate isomerase deficiency associated with two novel mutations in TPI gene
Authors: Fermo Elisa , Bianchi Paola , Vercellati Cristina , Rees David C. , Marcello Anna P. , Barcellini Wilma , Zanella Alberto 
Published: March 2010

AbstractWe report the clinical, haematological and molecular characteristics of two triose phosphate isomerase deficient patients affected by haemolytic anaemia and neuromuscular impairment. The sequence of complete TPI gene showed the presence of two previously undescribed mutations: c.722 T>C (Phe240Ser) and c.28 insG; each of the two unrelated patients showed the new mutation in compound heterozygosity with the most common variant Glu104Asp. The association of Glu104Asp with c.28 insG resulted in a very severe clinical pattern.
Effects of transportation during the hot season, breed and electrical stimulation on histochemical and meat quality characteristics of goat longissimus muscle
Authors: KADIM Isam T. , MAHGOUB Osman , AL‐MARZOOQI Waleed , KHALAF Samera , AL‐SINAWI Shadia S. H. , AL‐AMRI Issa 
Published: March 2010

ABSTRACTThe effects of transportation and electrical stimulation (90 V) on physiological, histochemical and meat quality characteristics of two breeds of Omani goats were assessed. Twenty 1‐year‐old male goats from each breed (Batina and Dhofari) were divided into two groups: 3 h transported during the hot season (42°C day time temperature) and non‐transported. Animals were blood‐sampled before loading and prior to slaughter. Electrical stimulation was applied 20 min postmortem to 50% randomly selected carcasses of both breeds. Temperature and pH decline of the Longissimus was monitored. Ultimate pH, shear force, sarcomere length, myofibrillar fragmentation index, expressed juice, cooking loss and colour were measured from samples of Longissimus dorsi muscles. Electrical stimulation and transportation had a significant effect on most biochemical and meat quality characteristics of Longissimus dorsi. The transported goats had higher plasma cortisol (P < 0.01), adrenaline, nor‐adrenaline and dopamine concentrations (P < 0.05) than non‐transported goats. Electrical stimulation resulted in a significantly (P < 0.05) more rapid muscle pH fall during the first 12 h after slaughter. Muscles from electrically‐stimulated carcasses had significantly (P < 0.05) longer sarcomeres, lower shear force value, a lighter colour (higher L* value), higher expressed juice and myofibrillar fragmentation index than those from non‐stimulated ones. Meat from transported goats had significantly higher pH, expressed juice and shear force, but contained significantly lower sarcomere length and L* values than non‐transported goats. The proportion of the myosin ATPase staining did not change as a function of stimulation, transportation or breed. These results indicated that subjecting goats to transportation for 3 h under high ambient temperatures can generate major physiological and muscle metabolism responses. Electrical stimulation improved quality characteristics of meat from both groups. This indicates that electrical stimulation may reduce detrimental effects of transportation on meat quality of Omani goats.
Reviewing the Technical Designs for Experiments with Ultraviolet‐B Radiation and Impact on Photosynthesis, DNA and Secondary Metabolism
Authors: Xu Chenping , Sullivan Joe H. 
Published: March 2010

Abstract The ultraviolet‐B (UV‐B) portion of sunlight has received much attention in the last three decades, because radiation from this spectral region increases due to the stratospheric ozone depletion, which results from increases of chlorofluorocarbons in the atmosphere. Plant responses to UV‐B exposure vary greatly and the interpretation of and comparison between studies is hindered, mainly by the contrasting experimental conditions used and interactive factors such as low light levels and possible artifacts due to the artificial experimental conditions. It seems likely that increases in solar UV‐B radiation of the magnitude anticipated under current stratospheric ozone projections will not significantly inhibit photosynthesis and cause DNA damage in plants. This is in part due to the well‐evolved protection mechanisms present in most plant species. One of the significant plant responses to UV‐B is changes in foliar secondary chemistry, which could be translated into significant effects at higher trophic levels through plant‐herbivore interactions and decomposition. Enhanced UV‐B radiation due to stratospheric ozone depletion could also cause morphological changes that would affect competitive interactions, especially if contrasting UV‐B sensitivity exists among the competitors.
Novel Insights from Live‐imaging in Shoot Meristem Development
Authors: Sijacic Paja , Liu Zhongchi 
Published: March 2010

Abstract Microscopic imaging of fluorescent reporters for key meristem regulators in live tissues is emerging as a powerful technique, enabling researchers to observe dynamic spatial and temporal distribution of hormonal and developmental regulators in living cells. Aided by time‐lapse microphotography, new types of imaging acquisition and analysis software, and computational modeling, we are gaining significant insights into shoot apical meristem (SAM) behavior and function. This review is focused on summarizing recent advances in the understanding of SAM organization, development, and behavior derived from live‐imaging techniques. This includes the revelation of mechanical forces in microtubule‐controlled anisotropic growth, the role of the CLV‐WUS network in the specification of peripheral zone and central zone cells, the multiple feedback loops involving cytokinin in controlling WUS expression, auxin dynamics in determining the position of new primordia, and, finally, sequence of regulatory events leading to de novo assembly of shoots from callus in culture. Future studies toward formulating “digital SAM” that incorporates multi‐dimensional data ranging from images of SAM morphogenesis to a genome‐scale expression map of SAM will greatly enhance our ability to understand, predict, and manipulate SAM, containing the stem cells that give rise to all above ground parts of a plant.
Muscle metaboreflex control of the circulation during exercise
Authors: Boushel R. 
Published: March 2010

AbstractThis review covers the control of blood pressure, cardiac output and muscle blood flow by the muscle metaboreflex which involves chemically sensitive nerves located in muscle parenchyma activated by metabolites accumulating in the muscle during contraction. The efferent response to metaboreflex activation is an increase in sympathetic nerve activity that constricts the systemic vasculature and also evokes parallel inotropic and chronotropic effects on the heart to increase cardiac output. The metaboreflex elicits a significant blood pressure elevating response during exercise and functions to redistribute blood flow and blood volume. Regional specificity in the efferent response to the metaboreflex activated from either the leg or the arm is seen in the balance between signals for vasoconstriction to curtail blood flow and signals to increase cardiac output. The metaboreflex has dual functions. It can both elevate and decrease muscle blood flow depending on (1) the intensity and mode of contraction, (2) the limb in which the reflex is evoked, (3) the strength of the signal defined by the muscle mass, (4) the extent to which blood flow is redistributed from inactive vascular beds to increase central blood volume and (5) the extent to which cardiac output can be increased.
Prevalence and incidence rates of Crohn's disease in mainland China: A meta‐analysis of 55 years of research
Authors: ZHENG Jia Ju , ZHU Xia Shuang , HUANGFU Zhao , SHI Xiao Hua , GUO Zhi Rong 
Published: March 2010

OBJECTIVES:  To better understand the occurrence of Crohn's disease in mainland China and to give an updated overview of the current status of the disease.METHODS:  We previously performed a computer‐based literature search using 50 years of records from the Chinese Database of Biology and Medicine (1979 to 2002), combined with a manual year‐by‐year search of the literature from 1950 to 1978. Using a similar method, descriptive epidemiological data of the last 5 years (2003 to September 2007) were collected, pooled with our previous data and re‐analyzed.RESULTS:  In total, 3618 cases of Crohn's disease since 1950 have been reported from 29 provinces and cities in mainland China, comprising 2112 male and 1506 female patients, with a male predominance of 1.40:1. More than 75 percent of the patients were aged from 20 to 50 years old, with a mean age of 36.9 ± 4.4 (1– 84) years. The extrapolated disease incidence and prevalence rates are 0.848/105 and 2.29/105 person/year, respectively.CONCLUSION:  The incidence and prevalence rates of Crohn's disease have been increasing rapidly, and the disease is no longer uncommon in China, but these rates are still lower than those in developed countries and other Asian countries. An underestimation may occur because patients who were misdiagnosed or did not seek medical advice could not be included in the study. A future population‐based survey is warranted.
Correlation of pulmonary function variables with hemodynamic measurements in patients with pulmonary arterial hypertension
Authors: Arunthari Vichaya , Burger Charles Dwayne , Lee Augustine Sung‐hi 
Published: March 2010

AbstractIntroduction:  A reduced diffusing capacity of the lung for carbon monoxide (DLCO) measured during a pulmonary function test can suggest pulmonary arterial hypertension (PAH). The DLCO has been reported to weakly correlate with pulmonary hemodynamics.Objective:  To determine whether the relationship between the DLCO and pulmonary arterial pressures can be strengthened by normalizing the DLCO to spirometric variables.Patient and Methods:  Patients were seen at a tertiary care referral center. Consecutive subjects who underwent right heart catheterization (RHC) for the evaluation of suspected PAH from 01 January 1991 through 01 October 2006 were identified. Pulmonary function testing (PFT) data performed within 60 days of the RHC was collected. Spearman rank correlation between PFT and RHC variables was calculated.Results:  One hundred thirty‐eight patients who had an RHC performed had complete PFTs available. No significant correlation was identified between the mean pulmonary artery pressure and the pulmonary vascular resistance against the DLCO, nor the DLCO when normalized to: forced expiratory volume in 1 s, forced vital capacity, total lung capacity or alveolar volume. Spirometric subgroups were identified by standard definitions of restrictive and/or obstructive ventilatory defects. Clinical subgroups were classified based on the clinically diagnosed cause of the patient's PAH. Again, no significant correlation was identified between the PFT variables and RHC measurements in these stratified subgroups.Conclusion:  In patients with suspected PAH, invasive hemodynamic measurements of PAH do not correlate with PFT variables, even when corrected for spirometric volumes, and regardless of the subgroup of ventilatory physiology or clinical diagnosis.Please cite this paper as: Arunthari V, Burger CD and Lee AS. Correlation of pulmonary function variables with hemodynamic measurements in patients with pulmonary arterial hypertension. Clin Respir J 2011; 5: 35–43.
Predictors of long‐term survival of lung cancer patients in a Norwegian community
Authors: Skaug Knut , Eide Geir Egil , Gulsvik Amund 
Published: March 2010

AbstractIntroduction: Few population‐based studies are available on more than 5 years survival of lung cancer patients.Objectives: The aims of this report were to study the survival and the predictors of survival in all lung cancer patients in a defined population and to determine whether and how the length of time from symptom onset to confirmed diagnosis (delay time) influenced survival.Methods: In a retrospective study, all incident cases from the Norwegian Cancer Registry and the hospital records in the Haugalandet area from 1990 to 1996 were followed until 31 December 2008. The dates of symptom onset, diagnosis, and death and information about demographics, initial stage, performance status, histology and initial symptoms were recorded.Results: Of a total of 271 patients, 57 (21%) were women, and the mean age at diagnosis was 67.4 years. One‐year survival was 29.2%, and five‐ and 10‐year survival was 8.5% and 5.5%, respectively. The median (inter quartile range, IQR) survival time was 5.7 (1.9, 14.1) months and the median (IQR) delay time was 2.2 (1.1, 3.7) months. Twenty‐five patients (10% of those who died) had a non‐lung cancer cause of death. No weight loss at the time of diagnosis was a significant predictor for long survival in addition to younger age, limited stage, good functional performance and surgical treatment, but delay time for diagnosis had no effect on survival time for lung cancer.Conclusion: In the whole population of lung cancer patients, long‐term survival remains poor and is not influenced by the diagnostic delay time.Please cite this paper as: Skaug K, Eide GE and Gulsvik A. Predictors of long‐term survival of lung cancer patients in a Norwegian community.Clin Respir J2011; 5: 50–58.
Dendritic cells fused with allogeneic hepatocellular carcinoma cell line compared with fused autologous tumor cells as hepatocellular carcinoma vaccines
Authors: Yang Jing‐Yue , Cao Da‐Yong , Ma Long‐Yang , Liu Wen‐Chao 
Published: March 2010

Purpose:  To investigate the specific antitumor responses against autologous hepatocellular carcinoma (HCC) cells of dendritic cells (DCs) fused with allogeneic HCC cell line, and evaluated the feasibility of BEL7402 as an alternative strategy to deliver shared HCC antigens to DCs.Methods:  Previous studies demonstrated fusions of patient‐derived DCs and autologous tumor cells could induce T‐cell responses against autologous tumors. These fusion cells require patient‐derived tumor cells, which are not, however, always available. Here, we report the fusing of autologous DCs with allogeneic HCC cell line to induced cytotoxic T‐lymphocyte (CTL) response against autologous HCC cells compare with autologous tumor cells.Results:  These DC/ BEL7402 fusion cells co‐expressed tumor‐associated antigens and DC‐derived costimulatory and major histocompatibility complex molecules. Both CD4+ and CD8 T+ cells were activated by the fusion cells as demonstrated by the proliferation of T‐cells, the production of cytokines and the simultaneous induction of specific CTL responses. Significantly, CTL induced by dendritic cell/allogeneic BEL7402 fusion cells were able to kill autologous HCC cells by human leukocyte antigen‐A2 restricted mechanisms. The results did not show significant difference between DC fusion with autologous hepatocellular carcinoma cells and DC fusion with allogeneic hepatocellular carcinoma cell line.Conclusions:  The fusion of allogeneic HCC cell line and autologous DCs may have applications in antitumor immunotherapy through cross‐priming against shared tumor antigens and may provide a platform for adoptive immunotherapy.
Effect of genipin on cholestasis induced by estradiol‐17β‐glucuronide and lithocholate‐3‐O‐glucuornide in rats
Authors: Goto Hideaki , Takikawa Hajime 
Published: March 2010

Aim:  Genipin is reported to stimulate the insertion of multidrug resistance protein 2 (Mrp2) in the bile canalicular membrane, thereby causing choleresis by the increased the biliary excretion of glutathione, which has been considered to be a substrate of Mrp2. In the present study, we examined the effect of genipin on cholestasis induced by estradiol‐17β‐glucuronide and lithocholate‐3‐O‐glucuronide, Mrp2 substrates, in rats. Further, the effect of genipin on the biliary excretion of substrates of P‐glycoprotein (P‐gp), vinblastine and erythromycin, was also studied.Methods:  The effect of genipin infusion at the rate of 0.5 µmol/min/100 g on cholestasis induced by estradiol‐17β‐glucuronide (0.075 µmol/min/100 g for 20 min) and lithocholate‐3‐O‐glucuronide (0.15 µmol/min/100 g for 40 min) was studied. The effect of genipin infusion on the biliary excretion of a tracer dose of vinblastine and erythromycin infused at the rate of 0.1 µmol/min/100 g was also studied.Results:  Genipin relieved estradiol‐17β‐glucuronide‐induced cholestasis, and cumulative biliary estradiol‐17β‐glucuronide excretion for 120 min was increased from 50 ± 20%–81 ± 20% dose. In contrast, genipin had no effect on lithocholate‐3‐O‐glucuronide‐induced cholestasis. Biliary excretion of a tracer dose of vinblastine and the maximum biliary excretion of erythromycin were significantly decreased by genipin.Conclusions:  Genipin protected estradiol‐17β‐glucuronide‐induced cholestasis. The mechanism of the protection of cholestasis by genipin is unknown, but it is speculated to be due to a conformational change of P‐gp by genipin, in addition to the stimulation of Mrp2 insertion into the bile canaliculi.
A Risk-Informed Approach to Leak-Before-Break Assessment of Pressure Tubes in CANDU Reactors
Authors: Pandey M. D. , Sahoo A. K. 
Published: March 2010

Abstract
The leak-before-break (LBB) assessment of pressure tubes is intended to demonstrate that in the event of through-wall cracking of the tube, there will be sufficient time followed by the leak detection, for a controlled shutdown of the reactor prior to the rupture of the pressure tube. CSA Standard N285.8 (2005, “Technical Requirements for In-Service Evaluation of Zirconium Alloy Pressure Tubes in CANDU Reactors,” Canadian Standards Association) has specified deterministic and probabilistic methods for LBB assessment. Although the deterministic method is simple, the associated degree of conservatism is not quantified and it does not provide a risk-informed basis for the fitness for service assessment. On the other hand, full probabilistic methods based on simulations require excessive amount of information and computation time, making them impractical for routine LBB assessment work. This paper presents an innovative, semiprobabilistic method that bridges the gap between a simple deterministic analysis and complex simulations. In the proposed method, a deterministic criterion of CSA Standard N285.8 is calibrated to specified target probabilities of pressure tube rupture based on the concept of partial factors. This paper also highlights the conservatism associated with the current CSA Standard. The main advantage of the proposed approach is that it retains the simplicity of the deterministic method, yet it provides a practical, risk-informed basis for LBB assessment.
Interplay between
Clostridium thermocellum
Family 48 and Family 9 Cellulases in Cellulosomal versus Noncellulosomal States
Authors: Vazana Yael , Moraïs Sarah , Barak Yoav , Lamed Raphael , Bayer Edward A. 
Published: March 2010

ABSTRACT

The anaerobic, thermophilic cellulolytic bacterium
Clostridium thermocellum
is known for its elaborate cellulosome complex, but it also produces a separate free cellulase system. Among the free enzymes, the noncellulosomal enzyme Cel9I is a processive endoglucanase whose sequence and architecture are very similar to those of the cellulosomal enzyme Cel9R; likewise, the noncellulosomal exoglucanase Cel48Y is analogous to the principal cellulosomal enzyme Cel48S. In this study we used the designer cellulosome approach to examine the interplay of prominent cellulosomal and noncellulosomal cellulases from
C. thermocellum
. Toward this end, we converted the cellulosomal enzymes to noncellulosomal chimeras by swapping the dockerin module of the cellulosomal enzymes with a carbohydrate-binding module from the free enzyme analogues and
vice versa
. This enabled us to study the importance of the targeting effect of the free enzymes due to their carbohydrate-binding module and the proximity effect for cellulases on the designer cellulosome.
C. thermocellum
is the only cellulosome-producing bacterium known to express two different glycoside hydrolase family 48 enzymes and thus the only bacterial system that can currently be used for such studies. The different activities with crystalline cellulose were examined, and the results demonstrated that the individual chimeric cellulases were essentially equivalent to the corresponding wild-type analogues. The wild-type cellulases displayed a synergism of about 1.5-fold; the cellulosomal pair acted synergistically when they were converted into free enzymes, whereas the free enzymes acted synergistically mainly in the wild-type state. The targeting effect was found to be the major factor responsible for the elevated activity observed for these specific enzyme combinations, whereas the proximity effect appeared to play a negligible role.