bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of inositol biosynthesis through targeted mutagenesis in Dictyostelium discoideum: generation and characterization of inositol-auxotrophic mutants
Authors: Fischbach Andreas , Adelt Stephan , Müller Alexander , Vogel Günter 
Published: July 2006

myo-Inositol and its downstream metabolites participate in diverse physiological processes. Nevertheless, considering their variety, it is likely that additional roles are yet to be uncovered. Biosynthesis of myo-inositol takes place via an evolutionarily conserved metabolic pathway and is strictly dependent on inositol-3-phosphate synthase (EC 5.5.1.4). Genetic manipulation of this enzyme will disrupt the cellular inositol supply. Two methods, based on gene deletion and antisense strategy, were used to generate mutants of the cellular slime mould Dictyostelium discoideum. These mutants are inositol-auxotrophic and show phenotypic changes under inositol starvation. One remarkable attribute is their inability to live by phagocytosis of bacteria, which is the exclusive nutrient source in their natural environment. Cultivated on fluid medium, the mutants lose their viability when deprived of inositol for longer than 24 h. Here, we report a study of the alterations in the first 24 h in cellular inositol, inositol phosphate and phosphoinositide concentrations, whereby a rapidly accumulating phosphorylated compound was detected. After its identification as 2,3-BPG (2,3-bisphosphoglycerate), evidence could be found that the internal disturbances of inositol homoeostasis trigger the accumulation. In a first attempt to characterize this as a physiologically relevant response, the efficient in vitro inhibition of a D. discoideum inositol-polyphosphate 5-phosphatase (EC 3.1.3.56) by 2,3-BPG is presented.
Intravenous hydration with a 2.5% glucose solution in Type II diabetes
Authors: Sjöstrand Fredrik , Nyström Thomas , Hahn Robert G. 
Published: July 2006

Physicians are often unclear about how fast intravenous glucose solutions should be administered to adequately hydrate patients with Type II diabetes while avoiding hyperglycaemia and excessive plasma volume expansion. The aim of the present study was to analyse the disposition of a 2.5% glucose solution and create a nomogram which could serve as a guide to fluid therapy in these patients. Twelve males (mean body mass index, 29 kg/m2) with Type II diabetes due to insulin resistance, as quantified by an euglycaemic hyperinsulinaemic glucose clamp, received an infusion of iso-osmotic 2.5% glucose solution with electrolytes (70 mmol/l sodium, 45 mmol/l chloride and 25 mmol/l acetate) at individual rates over 30 and 60 min respectively. Blood glucose and haemoglobin levels were measured repeatedly over 3.5 h to estimate the kinetics of glucose and fluid volume. Mean insulin sensitivity was 4.2×10−4 dl·kg−1·min−1·(μ-units/ml)−1. The individualized infusion rates reached the predetermined blood glucose level of 12 mmol/l with a mean difference of 0.2 mmol/l. The disposition of glucose was an important factor governing fluid distribution. The volume of distribution of exogenous glucose averaged 19.8 litres, but for the fluid volume it was only 3.7 litres. The clearance was 0.37 litre/min for glucose and 0.10 litre/min for the fluid volume, and the results of the 30-min and 60-min infusions agreed reasonably well. It is concluded that kinetic analysis can be used to guide the infusion time and infusion rate of 2.5% glucose to reach any predetermined glucose level and volume expansion.
Detection of elevated pulmonary capillary wedge pressure in elderly patients with various cardiac disorders by the Valsalva manoeuvre
Authors: Remmen Jaap J. , Aengevaeren Wim R. M. , Verheugt Freek W. A. , Jansen René W. M. M. 
Published: July 2006

In the present study, we assessed whether elevated (≥15 mmHg) PCWP (pulmonary capillary wedge pressure) can be detected using the blood pressure response to the Valsalva manoeuvre in a group of elderly patients with various cardiac disorders, including atrial fibrillation and valvular heart disease, and healthy elderly controls. The Valsalva manoeuvre was performed in 93 patients (71±4 years) and 28 healthy controls (70±4 years) undergoing right-sided cardiac catheterization. Blood pressure was measured non-invasively with Finapres. PPR (pulse pressure ratio), the ratio of minimum pulse pressure during phase 2 and maximum pulse pressure during phase 1 of the Valsalva manoeuvre, was correlated with PCWP (r=0.63, P&lt;0.001). The area under the receiver operator characteristic curve of PPR with elevated PCWP was 0.85 (P&lt;0.001). For PPR=0.62, sensitivity for elevated PCWP was 80%, specificity was 79%, positive predictive value was 76% and negative predictive value was 83%. Correlation of PPR with PCWP and the ability of PPR to detect elevated PCWP was present in atrial fibrillation, heart failure and valvular heart disease. In conclusion, PPR is a sensitive and specific instrument to diagnose elevated PCWP non-invasively in a large group of elderly patients with various cardiac disorders. This makes the Valsalva manoeuvre a useful non-invasive tool for diagnosing heart failure, applicable in elderly patients with common cardiac disorders, such as atrial fibrillation and valvular heart disease.
White blood cell and hormonal responses to 4300 m altitude before and after intermittent altitude exposure
Authors: Beidleman Beth A. , Muza Stephen R. , Fulco Charles S. , Cymerman Allen , Staab Janet E. , Sawka Michael N. , Lewis Steven F. , Skrinar Gary S. 
Published: July 2006

Recent studies have demonstrated that brief daily IAE (intermittent altitude exposure) was equally as effective as continuous altitude residence in inducing physiological adaptations consistent with altitude acclimatization. Although the positive benefits of IAE have been clearly defined, the potential negative consequences of IAE on health, specifically the immune system, remain undefined. The present study determined the effects of IAE on WBC (white blood cell) and hormonal responses during rest and exercise at 4300 m altitude. Six lowlanders (age, 23±2 years; body weight, 77±6 kg; values are means±S.E.M.) completed a V̇O2max (maximal O2 uptake) and submaximal cycle ergometer test during a 30-h SL (sea level) exposure and during a 30 h exposure to 4300 m altitude-equivalent once before (PreIAE) and once after (PostIAE) a 3-week period of IAE (4 h·day−1, 5 days·week−1, 4300 m). The submaximal cycle ergometer test consisted of two consecutive 15-min work bouts at 40% and 70% of altitude-specific V̇O2max. Blood samples were obtained at rest and during both exercise work bouts for measurements of WBC count, leucocyte subset counts, cortisol, adrenaline (epinephrine) and noradrenaline (norepinephrine). WBC, neutrophil and lymphocyte counts increased significantly (P&lt;0.05) during rest and exercise from SL to PreIAE and decreased (P&lt;0.05) during rest and exercise from PreIAE to PostIAE. Monocyte counts decreased (P&lt;0.05) during rest and exercise from PreIAE to PostIAE, but eosinophil and basophil counts did not change. Cortisol, adrenaline and noradrenaline did not change during rest or exercise from SL to PreIAE or PostIAE, but all increased significantly (P&lt;0.05) from rest during the two work bouts. In conclusion, this type of IAE stimulus did not induce a hormonal stress response and did no harm in terms of activation of the immune system at altitude, as measured by WBC and leucocyte subset counts. This method of pre-acclimatization can therefore be highly recommended for inducing altitude acclimatization without the ‘altitude residency’ requirement.
Treatment of classic Kaposi's sarcoma‐associated lymphedema with elastic stockings
Authors: BRAMBILLA Lucia , TOURLAKI Athanasia , FERRUCCI Silvia , BRAMBATI Marinella , BONESCHI Vinicio 
Published: July 2006

ABSTRACTLymphedema of the lower extremities is a frequent complication of Kaposi's sarcoma (KS). Compressive therapy is the basis of treatment for lymphatic disorders, but to the authors’ knowledge, there are no controlled trials to evaluate its effectiveness in KS‐related lymphedema. Sixty‐five patients with classic KS‐associated lymphedema limited to below the knee were studied. Fifty patients received below‐knee elastic stockings, whereas the remaining 15 did not use any compressive device. Among treated patients, 60% (30/50) experienced a limb volume reduction, while 40% (20/50) had an increase of limb volume. In contrast, all patients (15/15) of the untreated group had an increase of limb volume. No correlation between lymphedema reduction and systemic or local chemotherapy was observed, supporting compressive therapy as the major strategy for the treatment of this condition. Our results suggest that elastic stockings may be important tools for the management of lymphedema associated to classic KS.
Clinical and pathological study of lichen‐planus‐like keratosis in China
Authors: ZHANG Qian , WANG Wen‐hui , ZHAO Min , SHEN Li , CHENG Ji‐hong , ZHANG Bao‐yuan , LI Lin‐feng 
Published: July 2006

ABSTRACTLichen‐planus‐like keratosis is usually diagnosed pathologically; rarely, a definitive diagnosis can be made grossly in the clinic. Only a few cases of lichen‐planus‐like keratosis have been reported in China. The purpose of this study was to investigate the clinical and pathological features of lichen‐planus‐like keratosis in China. Fifty cases of lichen‐planus‐like keratosis patients diagnosed pathologically during a 5‐year period in our clinic were analyzed. Clinical features were recorded. Sectioned specimens were subjected to hematoxylin and eosin staining to observe pathological changes. Results showed that there were 34 males and 16 females (ratio 2:1) with an average age of 61.2 years. Most of the lesions were single papules or plaques with rough surfaces. They were distributed on the face, larger than 1 cm, and dark red to brown in color. Only one case (2%) was considered to be lichen‐planus‐like keratosis clinically. By hematoxylin and eosin staining, solar lentigo and solar elastosis could be found in 68% and 32% of lichen‐planus‐like keratosis lesions, respectively. Eosinophil (42%) and plasma cell (36%) infiltration was also found frequently. Exoerythrocytes could be detected in 50% of the cases. Lichen‐planus‐like keratosis is not uncommon in clinical practice in China, the diagnosis of lichen‐planus‐like keratosis should be made by a combination of clinical manifestations and pathological changes. It is better to classify lichen‐planus‐like keratosis as a benign skin tumor. More attention should be paid to lichen‐planus‐like keratosis in China.
Angiokeratoma circumscriptum arranged in a systematized band‐like pattern suggesting mosaicism
Authors: BECHARA Falk Georges , HAPPLE Rudolf , ALTMEYER Peter , GRABBE Stephan , JANSEN Thomas 
Published: July 2006

ABSTRACTA 10‐year‐old girl with vascular lesions that had been present since birth is reported. Initially, small red macules were limited to the legs, but later the lesions became more extensive. A hyperkeratotic aspect of the lesional skin surface had developed at the age of 2 years. On clinical examination, hyperkeratotic vascular lesions in a band‐like distribution on the trunk, legs and face were observed. The type of lesion varied from discrete macules with no or slight hyperkeratosis to confluent, protruding verrucous plaques. The clinical and histopathological findings were consistent with a diagnosis of angiokeratoma circumscriptum. The systematized band‐like arrangement observed in the present case strongly supports the concept that angiokeratoma circumscriptum reflects a mosaic state of a mutation that is so far unknown.
Detection and quantification of Phytophthora ramorum, P. kernoviae, P. citricola and P. quercina in symptomatic leaves by multiplex real‐time PCR
Authors: SCHENA LEONARDO , HUGHES KELVIN J. D. , COOKE DAVID E. L. 
Published: July 2006

SUMMARYNew species of Phytophthora such as Phytophthora ramorum, P. kernoviae and P. quercina together with P. citricola are plant pathogens which impact on forest health, natural ecosystem stability and international trade. A real‐time multiplex PCR approach based on TaqMan PCR was developed to simultaneously identify and detect these four Phytophthora species. Specific primers and probes labelled with FAM (P. ramorum), Yakima Yellow (P. kernoviae), Rox (P. citricola) and Cy5 (P. quercina) were designed in different regions of the ras‐related protein (Ypt1) gene. A new set of Black Hole Quenchers (BHQ), which dissipate energy as heat rather than fluorescence, were utilized. The method proved to be highly specific in tests with target DNA from 72 Phytophthora isolates (35 species). For all pathogens, the detection limit was 100 fg of target DNA and was not improved utilizing a nested approach to provide a first round of amplification with Phytophthora spp.‐specific primers. Cycle threshold (Ct) values were linearly correlated with the concentration of the target DNA (correlation coefficients ranged from 0.947 to 0.996) and were not affected by the presence of plant extracts, indicating the appropriateness of the method for qualitative and quantitative analyses. Two universal primers and a TaqMan probe were also developed to evaluate the quality and quantity of extracted DNA and to avoid false negatives. The reliability of the entire procedure was assessed using both artificially and naturally infected leaves of a range of plant species. The method, combined with a rapid procedure for DNA extraction, proved to be rapid, reliable, sensitive and cost effective as multiple pathogens were detected within the same plant extract by using different primer/probe combinations.
Genetical genomics in livestock: potentials and pitfalls
Authors: Haley C. , De Koning D. J. 
Published: July 2006

SummaryGenetical genomics combines gene mapping and gene expression approaches to identify loci controlling gene expression (eQTLs) that may underlie functional trait variation. The combination of genomic tools has great potential to facilitate dissection of complex traits, but studies need careful design and interpretation. Here we explore both the potential and the pitfalls of this approach with illustrations from actual studies. There are now an appreciable number of studies in model species and even humans demonstrating the feasibility of genetical genomics. However, most studies are too limited in size and design to unlock the full potential of the approach. Limited statistical power of studies exacerbates the problem of detection of false‐positive eQTL and some reported results should be interpreted with caution. As one approach to more successful implementation of genetical genomics, we propose to combine expression studies with fine mapping of functional trait loci. This synergistic approach facilitates the implementation of genetical genomics for species without inbred resources but is equally applicable to model species. These properties make it particularly suitable for livestock populations where many QTL are already in the public domain and potentially very large pedigreed populations can be accessed.
Novel integrative genomics strategies to identify genes for complex traits
Authors: Schadt E. E. 
Published: July 2006

SummaryForward genetics is a common approach to dissecting complex traits like common human diseases. The ultimate aim of this approach was the identification of genes that are causal for disease or other phenotypes of interest. However, the forward genetics approach is by definition restricted to the identification of genes that have incurred mutations over the course of evolution or that incurred mutations as a result of chemical mutagenesis, and that as a result lead to disease or to variations in other phenotypes of interest. Genes that harbour no such mutations, but that play key roles in parts of the biological network that lead to disease, are systematically missed by this class of approaches. Recently, a class of novel integrative genomics approaches has been devised to elucidate the complexity of common human diseases by intersecting genotypic, molecular profiling, and clinical data in segregating populations. These novel approaches take a more holistic view of biological systems and leverage the vast network of gene–gene interactions, in combination with DNA variation data, to establish causal relationships among molecular profiling traits and Fbetween molecular profiling and disease (or other classic phenotypes). A number of novel genes for disease phenotypes have been identified as a result of these approaches, highlighting the utility of integrating orthogonal sources of data to get at the underlying causes of disease.
From ‘omes to biology
Authors: Quackenbush J. 
Published: July 2006

SummaryTechnologies that have emerged from the genome project have dramatically increased our ability to generate data on the way in which organisms respond to their environments, how they execute their programmes of development and growth, and how these are altered in the development of disease states. However, our ability to analyse these large datasets has not kept pace with our ability to generate them and consequently new strategies must be developed to address the issues associated with their analysis. One approach that we have employed quite successfully is to look at data from microarrays (or proteomics or metabolomics experiments) not as independent datasets, but rather as elements of a much larger body of biological information across various scales that must be integrated with, and interpreted within, the context of such ancillary data. Here we outline the general approach and provide three examples from published studies of the way in which we have applied this strategy.
Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy
Authors: Van Zanten A. R. H. , Oudijk M. , Nohlmans‐Paulssen M. K. E. , Van Der Meer Y. G. , Girbes A. R. J. , Polderman K. H. 
Published: July 2006

AimTo compare the pharmacokinetics/pharmacodynamics, antibiotic resistance and clinical efficacy of continuous (CA) vs. intermittent administration (IA) of cefotaxime in patients with obstructive pulmonary disease and respiratory infections.MethodsA randomized controlled prospective nonblinded study was performed in 93 consecutive hospitalized patients requiring antibiotics for acute exacerbations of chronic obstructive pulmonary disease. Forty‐seven patients received 2 g of cefotaxime intravenously over 24 h plus a loading dose of 1 g, and 46 patients were given the drug intermittently (1 g three times daily).ResultsSimilar pathogens were identified in both groups, being mostly Haemophilus influenzae (51%), Streptococcus pneumoniae (21%) and Moraxella catharralis (18%). Mean minimal inhibitory concentration (MIC) values were also similar before and after treatment in both groups. Clinical cure was achieved in 37/40 (93%) (CA) vs. 40/43 (93%) (IA) of patients (P = 0.93). In microbiologically evaluable patients, criteria such as 70% of treatment time with antibiotic concentrations ≥ MIC (CA 100%vs. IA 60% of patients) and/or ≥ 5 × MIC (CA 100%vs. IA 55% of patients) were significantly better following continuous administration (P < 0.01). Samples with suboptimal antibiotic concentrations were found in 0% of CA vs. 65% of IA patients (P < 0.01).ConclusionsAlthough clinical cure rates were comparable, continuous cefotaxime administration led to significantly greater proportions of concentrations > MIC and > 5 × MIC compared with intermittent dosing. Continuous administration of cefotaxime at a lower dose [2 g (CA) vs. 3 g (CI)] is equally effective pharmacodynamically and microbiologically, may be more cost‐effective and offers at least the same clinical efficacy. Based on these observations, we recommend continuous administration of cefotaxime as the preferred mode of administration.
Evaluating the self‐initialization procedure for large‐scale ecosystem models
Authors: PIETSCH STEPHAN A. , HASENAUER HUBERT 
Published: July 2006

AbstractSelf‐initialization routines generate starting values for large‐scale ecosystem model applications which are needed to model transient behaviour. In this paper we evaluate the self‐initialization procedure of a large‐scale BGC‐model for biological realism by comparing model predictions with observations from the central European virgin forest reserve Rothwald, a category I IUCN wilderness area. Results indicate that standard self‐initialization towards a ‘steady state’ produces biased and inconsistent predictions resulting in systematically overestimated C and N pools vs. observations. We investigate the detected inconsistent predictions and use results to improve the self‐initialization routine by developing a dynamic mortality model which addresses natural forest dynamics with higher mortality rates during senescence and regeneration vs. lower mortality rates during the period of optimum forest growth between regeneration and senescence. Running self‐initialization with this new dynamic mortality model resulted in consistent and unbiased model predictions compared with field observations.
Estimating soil carbon sequestration under elevated CO2 by combining carbon isotope labelling with soil carbon cycle modelling
Authors: NIKLAUS PASCAL A. , FALLOON PETE 
Published: July 2006

AbstractElevated CO2 concentrations generally stimulate grassland productivity, but herbaceous plants have only a limited capacity to sequester extra carbon (C) in biomass. However, increased primary productivity under elevated CO2 could result in increased transfer of C into soils where it could be stored for prolonged periods and exercise a negative feedback on the rise in atmospheric CO2.Measuring soil C sequestration directly is notoriously difficult for a number of methodological reasons. Here, we present a method that combines C isotope labelling with soil C cycle modelling to partition net soil sequestration into changes in new C fixed over the experimental duration (Cnew) and pre‐experimental C (Cold). This partitioning is advantageous because the Cnew accumulates whereas Cold is lost in the course of time (ΔCnew>0 whereas ΔCold<0).We applied this method to calcareous grassland exposed to 600 μL CO2 L−1 for 6 years. The CO2 used for atmospheric enrichment was depleted in 13C relative to the background atmosphere, and this distinct isotopic signature was used to quantify net soil Cnew fluxes under elevated CO2. Using 13C/12C mass balance and inverse modelling, the Rothamsted model ‘RothC’ predicted gross soil Cnew inputs under elevated CO2 and the decomposition of Cold. The modelled soil C pools and fluxes were in good agreement with experimental data. C isotope data indicated a net sequestration of ≈90 g Cnew m−2 yr−1 in elevated CO2. Accounting for Cold‐losses, this figure was reduced to ≈30 g C m−2 yr−1 at elevated CO2; the elevated CO2‐effect on net C sequestration was in the range of≈10 g C m−2 yr−1. A sensitivity and error analysis suggests that the modelled data are relatively robust. However, elevated CO2‐specific mechanisms may necessitate a separate parameterization at ambient and elevated CO2; these include increased soil moisture due to reduced leaf conductance, soil disaggregation as a consequence of increased soil moisture, and priming effects. These effects could accelerate decomposition of Cold in elevated CO2 so that the CO2 enrichment effect may be zero or even negative. Overall, our findings suggest that the C sequestration potential of this grassland under elevated CO2 is rather limited.