bluuebunny/crossref_metadata_2025_split huggingface dataset:
Some Effects of Thiamine Deficiency and Reduced Caloric Intake on “Behaviour under Stress” and on Learning
Authors: Knopfelmacher F. , Khairy Melek , Russell R. W. , Yudkin John 
Published: April 2008

The main purpose of the investigation was to determine the effects of thiamine deficiency in rats on behaviour under stress and on learning. Since thiamine deficiency reduces food intake, it was necessary to have two control groups. The first received adequate thiamine, but a food intake reduced to that of the vitamin-deficient animals; the second received adequate thiamine and an unrestricted food intake. It was thus possible to study the effects both of thiamine deficiency and of reduced caloric intake on the behaviour variables measured. The experimental group was maintained on a thiamine-deficient diet throughout the entire experimental period. Because of the effects of thiamine deficiency on caloric intake, food-hunger was never used as a form of motivation. Behaviour in four different situations was studied: in Hall's open-field test, in two discrimination situations both involving exposure to insoluble and soluble problems, and in a water maze. Contrary to the findings of several previous studies, there were no significant effects of thiamine deficiency on behaviour prior to the onset of polyneuritis with its debilitating effects on motor co-ordination. There was also no evidence of impairment in any of the behaviour studied which could be attributed to restrictions in caloric intake. This was the case even though the restrictions continued for a period of somewhat more than twelve months. Although these restrictions did not lead to impairment they were associated with certain changes in performance. Animals whose feeding was restricted were more active and, during the soluble phase of one discrimination situation, showed more vicarious trial and error and learned more readily than animals fed ad libitum on the same diet. It is suggested that these differences may be interpreted in terms of the effects of what previous investigators have referred to as “irrelevant drives”.
Probabilistic multi-class multi-kernel learning: on protein fold recognition and remote homology detection
Authors: Damoulas Theodoros , Girolami Mark A. 
Published: April 2008

AbstractMotivation: The problems of protein fold recognition and remote homology detection have recently attracted a great deal of interest as they represent challenging multi-feature multi-class problems for which modern pattern recognition methods achieve only modest levels of performance. As with many pattern recognition problems, there are multiple feature spaces or groups of attributes available, such as global characteristics like the amino-acid composition (C), predicted secondary structure (S), hydrophobicity (H), van der Waals volume (V), polarity (P), polarizability (Z), as well as attributes derived from local sequence alignment such as the Smith–Waterman scores. This raises the need for a classification method that is able to assess the contribution of these potentially heterogeneous object descriptors while utilizing such information to improve predictive performance. To that end, we offer a single multi-class kernel machine that informatively combines the available feature groups and, as is demonstrated in this article, is able to provide the state-of-the-art in performance accuracy on the fold recognition problem. Furthermore, the proposed approach provides some insight by assessing the significance of recently introduced protein features and string kernels. The proposed method is well-founded within a Bayesian hierarchical framework and a variational Bayes approximation is derived which allows for efficient CPU processing times.Results: The best performance which we report on the SCOP PDB-40D benchmark data-set is a 70% accuracy by combining all the available feature groups from global protein characteristics but also including sequence-alignment features. We offer an 8% improvement on the best reported performance that combines multi-class k-nn classifiers while at the same time reducing computational costs and assessing the predictive power of the various available features. Furthermore, we examine the performance of our methodology on the SCOP 1.53 benchmark data-set that simulates remote homology detection and examine the combination of various state-of-the-art string kernels that have recently been proposed.Contact: theo@dcs.gla.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.
Choosing a Method for Phylogenetic Prediction
Authors: Mount David W. 
Published: April 2008

INTRODUCTIONThree methods--maximum parsimony, distance, and maximum likelihood--are generally used to find the evolutionary tree or trees that best account for the observed variation in a group of sequences. Each of these methods uses a different type of analysis. Programs based on distance methods are commonly used in the molecular biology laboratory because they are straightforward and can be used with a large number of sequences. Maximum likelihood methods are more challenging and require a greater understanding of the evolutionary models on which they are based. Because they involve so many computational steps and because the number of steps increases dramatically with the number of sequences, maximum likelihood programs are limited to a smaller number of sequences. They can be implemented on a supercomputer in order to analyze a greater number of sequences. This article presents an overview for the researcher who has a set of related sequences and wants to analyze them to predict the best trees that depict the phylogenetic relationships among the sequences.
In Planta Visualization of Protein Interactions Using Bimolecular Fluorescence Complementation (BiFC)
Authors: Waadt Rainer , Kudla Jörg 
Published: April 2008

INTRODUCTIONBimolecular fluorescence complementation (BiFC) analysis enables direct visualization of protein-protein interactions in living cells. This method has been successfully adapted to a variety of expression systems in different organisms. BiFC is based on the formation of a fluorescent complex by fragments of the enhanced yellow fluorescent protein (eYFP) when brought together by the interaction of two associating proteins fused to these fragments. Interaction of these proteins restores fluorescence and allows the visualization of spatial localization patterns of protein complexes. Absence of interaction prevents reassembly of the fluorescent protein and results only in background fluorescence. The specificity of bimolecular fluorescence complementation must be confirmed by parallel analysis of proteins in which the interaction interface has been mutated. This protocol describes the Agrobacterium-mediated transient expression protocol for BiFC assays in Nicotiana benthamiana leaf cells. This method exhibits a high transformation rate (up to 90% of the cells) and allows the simultaneous expression of multiple proteins in single cells. Therefore, this expression system enables colocalization analyses of fluorescently labeled proteins with the formation of BiFC complexes for determination of cellular complex localization. In addition, protein interaction assays in N. benthamiana leaves permit the investigation of protein interactions at different time points of expression, allow analysis of proteins that are normally toxic in protoplasts, and enable comparative protein interaction investigation in epidermal cells as well as in mesophyll protoplasts.
Secretory leukocyte peptidase inhibitor and lung cancer
Authors: Nukiwa Toshihiro , Suzuki Takuji , Fukuhara Tatsuro , Kikuchi Toshiaki 
Published: April 2008

Secretory leukocyte peptidase inhibitor (SLPI) belongs to the whey acidic protein four‐disulfide core family of proteins, and has antimicrobial and antiprotease functions. SLPI is produced by the epithelial cells lining the respiratory, digestive, and reproductive tracts. Gene‐targeting experiments in mice indicated that one function of SLPI is to protect proepithelin from elastase cleavage in wound healing. In addition to its antiprotease function, SLPI has an anti‐inflammatory function through the modulation of nuclear factor‐κB acting intracellularly, especially in macrophages. SLPI is also produced in cancer tissues, but its role in cancer is not well understood. SLPI genes are often upregulated under tumorigenic conditions. We found a negligible number of tumors in the lungs of SLPI knockout mice 20 or 40 weeks after administration of urethane, an interesting experimental model for investigating the function of SLPI in cancer. This review discusses the normal function of SLPI and its possible roles in cancer tissues. (Cancer Sci 2008; 99: 849–855)
Single‐institute phase 2 study of thalidomide treatment for refractory or relapsed multiple myeloma: Prognostic factors and unique toxicity profile
Authors: Hattori Yutaka , Okamoto Shin‐ichiro , Shimada Naoki , Kakimoto Tsunayuki , Morita Kunihiko , Tanigawara Yusuke , Ikeda Yasuo 
Published: April 2008

We previously reported a pilot study of thalidomide monotherapy for Japanese patients with refractory or relapsed multiple myeloma. In the present work, we have extended this clinical trial to a single‐institute phase 2 study with a larger number of patients and longer follow‐up time. New information on the optimal dose and prognostic factors as well as the correlation of toxicities with treatment schedule was obtained. Fifteen of 56 (27%) patients achieved a partial response, including three cases with near‐complete remission. Most patients suffered toxicities at a dose of 400 mg per day, but there was no clear dose–response relationship. Thus, a lower dose such as 200 mg per day or less is considered optimal. Multivariate analyses identified only lack of response to therapy as an adverse prognostic factor for progression‐free survival. Chromosomal abnormality, C‐reactive protein >10 mg/L, and more than six previous courses of chemotherapy were significantly associated with shorter overall survival. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 23 and 11% of patients, respectively. Grade 4 interstitial pneumonia and grade 5 pulmonary hypertension were observed; however, no patient suffered deep vein thrombosis, which has frequently been observed in other studies. Duration of therapy was closely related to the development of peripheral neuropathy. The efficacy and prognostic factors of this treatment were confirmed in long‐term observation. However, special attention should be paid to toxicities such as hematological and pulmonary complications as well as peripheral neuropathy in long‐term users. (Cancer Sci2008; 99: 1243–1250)
Estimation of the impact of noncompliance on pharmacokinetics: an analysis of the influence of dosing regimens
Authors: Hughes Dyfrig A. 
Published: April 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Patient compliance is better with formulations that require less frequent dosing than with formulations that require more frequent dosing.• Intramuscular risperidone and long‐acting oxybutynin are two examples of medicines reformulated for less frequent dosing.• However, it is not clear whether better compliance with less frequent dosing regimens translates to improved therapeutic outcome. WHAT THIS STUDY ADDS • At equivalent daily doses and typical patterns of compliance, fortnightly intramuscular depot administrations of risperidone provide better pharmacokinetic coverage than once‐daily oral dosing.• Once‐daily dosing of oxybutynin is no better at maintaining pharmacokinetic exposure than twice‐daily dosing at half strength.• The use of simulated compliance data as input to pharmacokinetic models is useful to assess the impact of noncompliance on internal drug exposure.AIMSTo determine whether, for oxybutynin and risperidone, drug exposure is better with less frequent dosing regimens than with regimens that require more frequent dosing.METHODSPharmacokinetic models of oxybutynin (5 mg twice‐daily and 10 mg once‐daily) and risperidone (2 mg once‐daily orally and 25 mg fortnightly intramuscular injection) were developed. Simulations of multiple doses were performed by use of stochastic models of dose‐taking compliance and clinic visit attendance.RESULTSAt therapeutic concentrations and with typical patterns of noncompliance, intramuscular injections of risperidone resulted in a 41% (SD 12%) greater pharmacokinetic coverage than the oral dose, 76% (SD 10%) vs. 35% (SD 7%). No discernable differences were evident between once‐ and twice‐daily formulations of oxybutynin, 29.2% (SD 10%) vs. 29.0% (SD 13%).CONCLUSIONSFor equivalent doses for each drug, the longer acting preparation of risperidone, but not oxybutynin, is pharmacokinetically more forgiving of noncompliance than the shorter acting counterparts. Further analysis is required to confirm whether these observations are valid clinically.
Thrombolysis or nothing for acute myocardial infarction? It's all the same!
Authors: Bertele' Vittorio , Angelici Laura , Barlera Simona , Garattini Silvio 
Published: April 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The methodological and ethical value of equivalence and non‐inferiority trials is questioned.• These studies are still increasingly used in drug evaluation and accepted by the scientific community and the regulatory authorities. WHAT THIS STUDY ADDS • By applying the hypothesis of an equivalence trial of saruplase and streptokinase (SK) we proved that the no‐thrombolysis approach in the GISSI trial was equivalent to thrombolysis with SK, i.e. death rates in patients given SK or not were similar enough to consider the no‐thrombolysis regimen equivalent to thrombolytic treatment.• These data illustrate the unreliability of equivalence trials, which can even disprove consolidated clinical evidence such as the efficacy of thrombolysis in acute myocardial infarction.• Equivalence trials should not be considered an option by the scientific community and should not be accepted as a basis for marketing authorization by the regulatory authorities.AIMSTo assess the reliability of equivalence trials we tested whether the no‐thrombolysis approach was equivalent to thrombolysis with streptokinase (SK) in acute myocardial infarction.METHODSWe applied the hypothesis of an equivalence trial of a recombinant plasminogen activator and SK to the GISSI‐1 control group.RESULTSIn at least one of three subsets randomly extracted from the GISSI database the equivalence criterion was satisfied, i.e. death rates in patients given SK or not were similar enough to consider the no‐thrombolysis regimen equivalent to thrombolytic treatment. Two‐thirds of 100 replications of the sampling gave this result.CONCLUSIONSThese findings suggest the unreliability of equivalence trials, which should neither be adopted by the scientific community nor accepted by the regulatory authorities.
Prognostic importance of T and NK‐cells in a consecutive series of newly diagnosed patients with chronic lymphocytic leukaemia
Authors: Palmer Shanique , Hanson Curtis A. , Zent Clive S. , Porrata Luis F. , LaPlant Betsy , Geyer Susan M. , Markovic Svetomir N. , Call Timothy G. , Bowen Deborah A. , Jelinek Diane F. , Kay Neil E. , Shanafelt Tait D. 
Published: April 2008

SummaryPatients with chronic lymphocytic leukaemia (CLL) have a variable clinical course. The identification of modifiable characteristics related to CLL‐specific survival may provide opportunities for therapeutic intervention. The absolute number of T‐cell and natural killer (NK)‐cells was calculated for 166 consecutive patients with CLL evaluated by flow cytometry at Mayo Clinic ≤2 months of diagnosis. The size of the T‐cell/NK‐cell compartment relative to the size of the malignant monoclonal B‐cell (MBC) compartment was evaluated by calculating NK:MBC and T:MBC ratios. Patients exhibited substantial variation in the absolute number of T‐ and NK‐cells as well as T:MBC and NK:MBC ratios at diagnosis. Higher T:MBC and NK:MBC ratios were observed among patients with early stage and mutated IGHV genes (all P ≤ 0·0003). As continuous variables, both T:MBC ratio (P‐value = 0·03) and NK:MBC ratio (P‐value = 0·02) were associated with time to treatment (TTT). On multivariate Cox modelling including stage, CD38, absolute MBC count, NK:MBC ratio and T:MBC ratio, the independent predictors of TTT were stage, T:MBC ratio and NK:MBC ratio. These findings suggest that measurable characteristics of the host immune system relate to the rate of disease progression in patients with newly diagnosed CLL. These characteristics can be modified and continued evaluation of immunomodulatory drugs, vaccination strategies and cellular therapies to delay/prevent disease progression are warranted.
Detection of chromium allergy by cellular in vitro methods
Authors: Lindemann M. , Rietschel F. , Zabel M. , Grosse‐Wilde H. 
Published: April 2008

SummaryBackground
The standard assay for the detection of chromium sensitization, the patch test, does not allow discrimination between patients with and without clinical symptoms of allergy.Objective
The aim of this study was to prove whether cellular in vitro tests are predictive of chromium allergy.Methods
Chromium‐sensitized volunteers with and without clinically manifest allergy and non‐sensitized healthy controls (n=37, 19, and 26, respectively) were analysed by cellular in vitro methods using tri‐ and hexavalent chromium (chromium chloride and potassium dichromate) as stimuli. The results were correlated with clinical and anamnestic data.Results
Sensitized individuals with an allergy displayed significantly higher lymphocyte transformation test (LTT) responses than sensitized volunteers without allergy and controls (P<0.05 and P<0.01, respectively). 12.5 μg/mL of chromium chloride and 50 ng/mL of potassium dichromate were found to be optimal to discriminate between sensitized individuals with and without allergy. Combining the results of chromium chloride and potassium dichromate LTT, a positive reaction to at least one of the stimuli was highly predictive of allergy [sensitization with vs. without allergy: Odds ratio (OR)=6.4, P=0.004; sensitization with allergy vs. controls: OR=11.5, P<0.0001]. On the contrary, IFN‐γ, IL‐2, IL‐4, IL‐10, and IL‐12 production to the ELISpot, patch test results, sensitization against other metals, and atopy score did not significantly discriminate between sensitization with and without allergy. However, IFN‐γ responses towards chromium chloride were significantly correlated with the strength of patch test reactivity (r=0.49, P=0.002). By IFN‐γ ELISpot, the average precursor cell frequency reactive to trivalent chromium could be defined as 26, 15, and 11 : 106 in volunteers with sensitization and allergy, with sensitization without allergy, and controls, respectively.Conclusions
In contrast to the patch test, the LTT appears to be a method that is predictive of chromium allergy.
Inhibition of inducible nitric oxide synthase activity prevents liver recovery in rat thioacetamide‐induced fibrosis reversal
Authors: Lukivskaya O. , Patsenker E. , Lis R. , Buko V. U. 
Published: April 2008

ABSTRACTBackground  Stimulation of nitric oxide (NO) synthesis similar to the application of NO donors could be of benefit in liver fibrosis. Many authors believe that activation of NO synthesis by pharmacological agents is promising in the treatment of liver fibrosis. However, there is considerable controversy in understanding the role of NO in fibrogenesis and fibrolysis. The aims of our study were to evaluate the effects of L‐arginine, as an NO metabolic precursor, and those of NO synthase (NOS) inhibitors, L‐nitroarginine methyl ester (L‐NAME) and aminoguanidine (AG) in rats with thioacetamide (TAA)‐induced liver fibrosis reversal.Materials and methods  Male Wistar rats, 230–240 g, received TAA (200 mg kg−1, intraperitoneally) twice a week for 3 months. Liver resolution was simulated by withdrawal of TAA administration. Thereafter the animals were subdivided into five groups and treated by intragastric intubation with: L‐arginine (100 and 300 mg kg−1); L‐NAME as an inhibitor of both constitutively expressed NOS (eNOS) and inducible NOS (iNOS) (20 mg kg−1), AG as a specific inhibitor of iNOS (100 mg kg−1) or placebo. The severity of liver fibrosis was assessed by morphometric evaluation of liver slides stained with Azan‐Mallory, hydroxyproline (Hyp) determination and mRNA steady state levels of collagen I, transforming growth factor (TGF)‐β1, metalloproteinases (MMP)‐13, ‐14, tissue inhibitor of MMP (TIMP)‐1 and plasminogen activator inhibitor (PAI)‐1 were quantified by real time PCR. The activities of serum marker enzyme, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, were measured.Results  TAA treatment during 3 months induced micronodular liver fibrosis with a pronounced deposition of collagen fibres. L‐Arginine did not affect this deposition nor did it affect both relative and total liver hydroxyproline content. Both NOS inhibitors significantly increased the square of the liver connective tissue stained by Azan‐Mallory and the above parameters characterizing liver hydroxyproline content. Both NOS inhibitors up‐regulated procollagen α1 (I), MMP‐13, TIMP‐1 and PAI‐1 mRNA expression. The AG effects were more pronounced. than those of L‐NAME. AG treatment also increased mRNA expression of TGF‐β1 and PAI‐1.Conclusions  Both NOS inhibitors developed a clear pro‐fibrotic effect in the liver. Aminoguanidine was more fibrotic than L‐NAME. Our data suggest a significant anti‐fibrotic role for iNOS rather than for eNOS. L‐Arginine did not show any anti‐fibrotic properties in the TAA‐model used.
Evaluation of the one‐minute exercise test to detect peripheral arterial disease
Authors: Hoogeveen E. K. , Mackaay A. J. C. , Beks P. J. , Kostense P. J. , Dekker J. M. , Heine R. J. , Nijpels G. , Rauwerda J. A. , Stehouwer C. D. A. 
Published: April 2008

ABSTRACTBackground   Asymptomatic peripheral arterial disease (PAD) is common amongst the elderly and is a risk factor for cardiovascular morbidity and mortality. PAD can be assessed by non‐invasive tests such as the ankle/brachial pressure index (ABPI) at rest and Doppler flow velocity (DFV) scanning, but these tests may underestimate the prevalence of PAD. The aim of this study was to estimate the added value, for the detection of PAD, of the one‐minute exercise test, defined as positive if the drop of the ankle systolic pressure was more than 30 mmHg. We also investigated whether the combination of the ABPI at rest and the one‐minute exercise test could replace DFV scanning.Materials and methods   We studied this in a random sample (n = 631) of a 50‐ to 75‐year‐old population.Results   Of these subjects 11% (66/631) had an abnormal ABPI (< 0·9) and 16% (102/631) had an abnormal DFV curve. Of this sample 72% of the subjects performed a one‐minute exercise test. Of all subjects 6% (27/451) had an abnormal ABPI (< 0·9) and 12% (54/451) had an abnormal DFV curve. The one‐minute exercise test revealed seven cases of PAD (beyond the 67 already identified) which were not detected by an abnormal ABPI at rest and/or DFV scanning. As a result the prevalence of PAD increased by 2%. All patients with an aortoiliac or femoropopliteal obstruction had an ABPI at rest < 0·9. The sensitivity of the combination of the ABPI at rest and the one‐minute exercise test to detect abnormal DFV curves was low for crural obstructions.Conclusion   The one‐minute exercise test slightly improves the detection of peripheral arterial disease in the general population.