bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modern classification of neoplasms: reconciling differences between morphologic and molecular approaches
Authors: Berman Jules 
Published: August 2005

Abstract

Background
For over 150 years, pathologists have relied on histomorphology to classify and diagnose neoplasms. Their success has been stunning, permitting the accurate diagnosis of thousands of different types of neoplasms using only a microscope and a trained eye. In the past two decades, cancer genomics has challenged the supremacy of histomorphology by identifying genetic alterations shared by morphologically diverse tumors and by finding genetic features that distinguish subgroups of morphologically homogeneous tumors.

Discussion
The Developmental Lineage Classification and Taxonomy of Neoplasms groups neoplasms by their embryologic origin. The putative value of this classification is based on the expectation that tumors of a common developmental lineage will share common metabolic pathways and common responses to drugs that target these pathways. The purpose of this manuscript is to show that grouping tumors according to their developmental lineage can reconcile certain fundamental discrepancies resulting from morphologic and molecular approaches to neoplasm classification.
In this study, six issues in tumor classification are described that exemplify the growing rift between morphologic and molecular approaches to tumor classification: 1) the morphologic separation between epithelial and non-epithelial tumors; 2) the grouping of tumors based on shared cellular functions; 3) the distinction between germ cell tumors and pluripotent tumors of non-germ cell origin; 4) the distinction between tumors that have lost their differentiation and tumors that arise from uncommitted stem cells; 5) the molecular properties shared by morphologically disparate tumors that have a common developmental lineage, and 6) the problem of re-classifying morphologically identical but clinically distinct subsets of tumors. The discussion of these issues in the context of describing different methods of tumor classification is intended to underscore the clinical value of a robust tumor classification.

Summary
A classification of neoplasms should guide the rational design and selection of a new generation of cancer medications targeted to metabolic pathways. Without a scientifically sound neoplasm classification, biological measurements on individual tumor samples cannot be generalized to class-related tumors, and constitutive properties common to a class of tumors cannot be distinguished from uninformative data in complex and chaotic biological systems. This paper discusses the importance of biological classification and examines several different approaches to the specific problem of tumor classification.
An evaluation of a morphine public health programme for cancer and AIDS pain relief in Sub-Saharan Africa
Authors: Logie Dorothy E , Harding Richard 
Published: August 2005

Abstract

Background
Despite growing HIV and cancer prevalence in Sub-Saharan Africa, and WHO advocacy for a public health approach to palliative care provision, opioid availability is severely limited. Uganda has achieved a morphine roll-out programme in partnership with the Ministry of Health. This study aimed to evaluate that programme by identifying challenges to implementation that may inform replication.

Methods
A multi-methods protocol appraised morphine regulation, storage, prescribing, and consumption in three phases: key informant interviews throughout the opioid supply chain, and direct observation and audit of clinical practice.

Results
Regulation had achieved its goal of preventing misuse and leakage from the supply chain. However, the Government felt that relaxation of regulation was now appropriate. Confusion and complexity in storage and authorisation rules led to discontinuation of opioid pain management at the patient level and also wasted service time in trying to obtain supplies to which they were entitled. Continued neglect to prescribe among clinicians and public fear of opioids led to under prescribing, and clinical skills showed some evidence of need for improvement with respect to physical assessment and follow-up.

Conclusion
The Ugandan programme offers a successful model for both advocacy and Governmental support in achieving opioid roll-out across health districts. Despite initial concerns, abuse of opioids has not been evident. Further work is required to ensure that available supplies of opioids are prescribed to those in need, and that clinical standards are met. However, the programme for roll-out has proved a useful model to expand opioid availability as the first step in improving patient care, and may prove a useful template for other Sub-Saharan African countries.
Relationship between Sialic acid and metabolic variables in Indian type 2 diabetic patients
Authors: Nayak B Shivananda , Bhaktha Geetha 
Published: August 2005

Abstract

Background
Plasma sialic acid is a marker of the acute phase response. Objective is to study the relationship between sialic acid relationship with metabolic variables in Indian type 2 diabetes with and without microvascular complications.

Research design and Methods
Fasting Venous blood samples were taken from 200 subjects of which 50 were of diabetes mellitus (DM) and nephropathy patients, 50 patients with type 2 diabetes and retinopathy, 50 patients with type 2 diabetes without any complications and 50 healthy individuals without diabetes. The Indian subject's aged 15–60 years with type 2 diabetes were recruited for the study. Simultaneously urine samples were also collected from each of the subjects. All the blood samples were analyzed for total cholesterol, triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting and postprandial glucose on fully automated analyzer. Serum and urine sialic acid along with microalbumin levels were also estimated.

Results
There was a significantly increasing trend of plasma and urine sialic acid with severity of nephropathy (P < 0.001) and with degree of urinary albumin excretion (P < 0.001). Serum sialic acid correlated with increasing serum creatinine concentration (P < 0.001). Elevated serum sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA1c, serum triglyceride and cholesterol concentrations, waist-to-hip ratio and hypertension. Significant correlations were found between sialic acid concentration and cardiovascular risk factors like LDL and TG in the diabetic subjects.

Conclusion
The main finding of this study is that elevated serum and urinary sialic acid and microalbumin concentrations were strongly related to the presence of microvascular complications like diabetic nephropathy and retinopathy and cardiovascular risk factors in Indian type 2 diabetic subjects. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.
Interferon-gamma alters the phagocytic activity of the mouse trophoblast
Authors: Albieri Andréa , Hoshida Mara S , Gagioti Sonia M , Leanza Eduardo C , Abrahamsohn Ises , Croy Anne , Ashkar Ali A , Bevilacqua Estela 
Published: August 2005

AbstractInterferon-gamma (IFN-gamma) mediates diverse functions in bone marrow-derived phagocytes, including phagocytosis and microbe destruction. This cytokine has also been detected at implantation sites under both physiological and pathological conditions in many different species. At these particular sites, the outermost embryonic cell layer in close contact with the maternal tissues, the trophoblast exhibits intense phagocytic activity. To determine whether IFN-gamma affects phagocytosis of mouse-trophoblast cells, ectoplacental cone-derived trophoblast was cultured and evaluated for erythrophagocytosis. Phagocytic activity was monitored ultrastructurally and expressed as percentage of phagocytic trophoblast in total trophoblast cells. Conditioned medium from concanavalin-A-stimulated spleen cells significantly enhanced trophoblast phagocytosis. This effect was blocked by pre-incubation with an anti-IFN-gamma neutralizing antibody. Introduction of mouse recombinant IFN-gamma (mrIFN-gamma) to cultures did not increase cell death, but augmented the percentage of phagocytic cells in a dose-dependent manner. Ectoplacental cones from mice deficient for IFN-gamma receptor alpha-chain showed a significant decrease of the phagocytosis, even under mrIFN-gamma stimulation, suggesting that IFN-gamma-induced phagocytosis are receptor-mediated. Reverse transcriptase-PCR analyses confirmed the presence of mRNA for IFN-gamma receptor alpha and beta-chains in trophoblast cells and detected a significant increase in the mRNA levels of IFN-gamma receptor beta-chain, mainly, when cultured cells were exposed to IFN-gamma. Immunohistochemistry and Western blot analyses also revealed protein expression of the IFN-gamma receptor alpha-chain. These results suggest that IFN-gamma may participate in the phagocytic activation of the mouse trophoblast, albeit the exact mechanism was not hereby elucidated. Protective and/or nutritional fetal benefit may result from this physiological response. In addition, our data also shed some light on the understanding of trophoblast tolerance to inflammatory/immune cytokines during normal gestation.
Drug Testing in Blood: Validated Negative-Ion Chemical Ionization Gas Chromatographic–Mass Spectrometric Assay for Enantioselective Measurement of the Designer Drugs MDEA, MDMA, and MDA and Its Application to Samples from a Controlled Study with MDMA
Authors: Peters Frank T , Samyn Nele , Lamers Caroline TJ , Riedel Wim J , Kraemer Thomas , de Boeck Gert , Maurer Hans H 
Published: August 2005

Abstract
Background: The enantiomers of the designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) differ in their pharmacologic and toxicologic potency. The aim of this study was to develop an assay for measuring these enantiomers in small plasma volumes and to analyze samples from a controlled study with MDMA.
Methods: The analytes were extracted from ≤0.2 mL of plasma by mixed-mode solid-phase extraction. After derivatization with S-(−)-heptafluorobutyrylprolyl chloride, the resulting diastereomers were separated by gas chromatography (HP-5MS) within 17 min and detected by mass spectrometry in the negative-ion chemical ionization mode. The method was fully validated and applied to samples from a controlled study in which a single dose of racemic MDMA (75 mg) was administered.
Results: The derivatized enantiomers were well separated and detected with good sensitivity. The assay was linear (per enantiomer) at 1–50 μg/L for MDA and 5–250 μg/L for MDMA and MDEA. Analytical recovery, accuracy, repeatability, and intermediate precision data were within required limits. Extraction yields were 82.1%–95.3%. In the study samples, concentrations of R-(−)-MDMA significantly exceeded those of S-(+)-MDMA. Their ratios (R vs S) were always &gt;1.0 and increased over time. Concentrations of S-(+)-MDA exceeded those of R-(−)-MDA, their ratios (R vs S) also increasing over time but remaining &lt;1.0.
Conclusions: This assay enables sensitive, reliable, and fast enantioselective measurement of MDA, MDMA, and MDEA in small volumes of plasma. The controlled study data confirm previous findings of MDMA and MDA enantiomer ratios (R vs S) increasing over time after ingestion of racemic MDMA.
Biological and environmental characterization of marine macroalgal assemblages in Potter Cove, South Shetland Islands, Antarctica
Authors: Quartino María L. , Zaixso Héctor E. , Boraso de Zaixso Alicia L. 
Published: August 2005

Abstract
We describe the macroalgal assemblages in Potter Cove and their distribution by depth, substratum, irradiation, nutrients, salinity, water temperature and light period. We determined groups by using K-means, the Hellinger index and the maximum Calinski-Harabasz pseudo-F-statistic as stopping rule. Indicator species were assessed with the IndVal index. Relationships between groups and environmental factors were determined by correspondence analysis, and results were validated by a canonical correspondence analysis of species and environment. To compare the group biodiversities we used species richness and diversity indices and abundance biomass comparisons curves. Analysis with incidence data discriminated one shallow Iridaea assemblage and one deep Himantothallus assemblage. Analysis using biomass discriminated three facies, the first in the upper zone (Iridaea cordata, Monostroma hariotii, Adenocystis utricularis, Enteromorpha bulbosa), the second (Desmarestia menziesii, D. antarctica, Ascoseira mirabilis, Curdiea racovitzae, Gigartina skottsbergii, Kallymenia antarctica, Neuroglossum delesseriae, Phaeurus antarcticus, Gymnogongrus turquetii) at intermediate depth and the third (H. grandifolius, D. anceps, Georgiella confluens, Ballia callitricha, Plocamium cartilagineum), coincident with the deep qualitative assemblage, was found in a less disturbed environment. The difference in species composition between the groups was mainly related to depth as an environmental variable. The high specific diversity at intermediate depths can be explained by the presence of patches in different successional stages caused by iceberg scouring.
Using Fish Biomarkers to Monitor Improvements in Environmental Quality
Authors: Facey Douglas E. , Blazer Vicki S. , Gasper Meredith M. , Turcotte Cynthia L. 
Published: August 2005

Abstract
The percentage of splenic tissue occupied by macrophage aggregates and hepatosomatic index (HSI) were evaluated in rock bass Ambloplites rupestris from Burlington Harbor, Vermont. In 1992, fish collected from the inner Burlington Harbor area had a significantly greater percentage of splenic tissue occupied by macrophage aggregates and greater HSI than did fish from reference sites. These biomarkers often are correlated with exposure to various contaminants (e.g., polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and some heavy metals, which were found in Burlington Harbor sediments during surveys in 1990 and 1991). Contaminants are believed to have entered Burlington Harbor through the city's main sewage treatment plant, which discharged effluent into the harbor for many years. In 1994, the city completed a significant upgrade of this treatment plant, which included an extension of the effluent pipe beyond the inner harbor area. In 1999, rock bass were again collected from Burlington Harbor as an index of whether there was any improvement in environmental quality. Our data showed a significantly lower percentage of splenic tissue occupied by macrophage aggregates and significantly lower HSI among nine age-4 rock bass in 1999 than among six age-4 rock bass in 1992. The significant changes in these biomarkers suggest decreased exposure to contaminants. Our study reinforces the value of macrophage aggregates and HSI as biomarkers of environmental contamination, and the correlation with remedial action shows their potential utility in documenting improvements in environmental conditions.
Juvenile onset Huntington disease resulting from a very large maternal expansion
Authors: Nahhas F.A. , Garbern J. , Krajewski K.M. , Roa B.B. , Feldman G.L. 
Published: August 2005

AbstractWe report a 5½‐year‐old girl with a maternal family history of Huntington disease (HD), who presented clinically with unbalanced gait, impaired speech, and increasing difficulty with fine motor control. Onset of symptoms began at the age of 3½ years. The suspected diagnosis of juvenile HD, based upon her family history, was confirmed by DNA analysis. At age 7, the patient died secondary to complications of her underlying disorder. Juvenile‐onset Huntington disease is uncommon, predominantly transmitted by fathers and is always associated with very large expansions of the CAG repeat. Interestingly, this patient inherited a large CAG size expansion from her mother, who herself had symptoms of HD at the age of 18. Molecular analysis revealed that the mother had 70 CAG repeats whereas our patient had ∼130 CAG repeats. This is the largest reported CAG expansion from a maternal transmission that has been confirmed molecularly and it demonstrates that very large expansions can also occur through the maternal lineage. © 2005 Wiley‐Liss, Inc.
Novel Fluorescent Phosphonic Acid Esters for Discrimination of Lipases and Esterases
Authors: Schmidinger Hannes , Birner‐Gruenberger Ruth , Riesenhuber Gernot , Saf Robert , Susani‐Etzerodt Heidrun , Hermetter Albin 
Published: August 2005

AbstractLipases and esterases are responsible for carboxylester hydrolysis inside and outside cells and are useful biocatalysts for (stereo)selective modification of synthetic substrates. Here we describe novel fluorescent suicide inhibitors that differ in structure and polarity for screening and discrimination of lipolytic enzymes in enzyme preparations. The inhibitors covalently react with the enzymes to form fluorescent lipid–protein complexes that can be resolved by gel electrophoresis. The selectivities of the inhibitors were determined by using different (phospho)lipase, esterase and cholesterol esterase preparations. The results indicate that formation of an inhibitor–enzyme complex is highly dependent on the chemical structure of the inhibitor. We identified inhibitors with very low specificity, and other derivatives that were highly specific for certain subgroups of lipolytic enzymes such as lipases and cholesterol esterases. A combination of these substrate‐analogous activity probes represents a useful toolbox for rapid identification and classification of serine hydrolase enzymes.
High‐Resolution Solid‐State NMR Studies on Uniformly [13C,15N]‐Labeled Ubiquitin
Authors: Seidel Karsten , Etzkorn Manuel , Heise Henrike , Becker Stefan , Baldus Marc 
Published: August 2005

AbstractUnderstanding of the effects of intermolecular interactions, molecular dynamics, and sample preparation on high‐resolution magic‐angle spinning NMR data is currently limited. Using the example of a uniformly [13C,15N]‐labeled sample of ubiquitin, we discuss solid‐state NMR methods tailored to the construction of 3D molecular structure and study the influence of solid‐phase protein preparation on solid‐state NMR spectra. A comparative analysis of 13C′, 13Cα, and 13Cβ resonance frequencies suggests that 13C chemical‐shift variations are most likely to occur in protein regions that exhibit an enhanced degree of molecular mobility. Our results can be refined by additional solid‐state NMR techniques and serve as a reference for ongoing efforts to characterize the structure and dynamics of (membrane) proteins, protein complexes, and other biomolecules by high‐resolution solid‐state NMR.
NMR Spectroscopy of Paramagnetic Metalloproteins
Authors: Bertini Ivano , Luchinat Claudio , Parigi Giacomo , Pierattelli Roberta 
Published: August 2005

AbstractThis article deals with the solution structure determination of paramagnetic metalloproteins by NMR spectroscopy. These proteins were believed not to be suitable for NMR investigations for structure determination until a decade ago, but eventually novel experiments and software protocols were developed, with the aim of making the approach suitable for the goal and as user‐friendly and safe as possible. In the article, we also give hints for the optimization of experiments with respect to each particular metal ion, with the aim of also providing a handy tool for nonspecialists. Finally, a section is dedicated to the significant progress made on 13C direct detection, which reduces the negative effects of paramagnetism and may constitute a new chapter in the whole field of NMR spectroscopy.
An Improvement in the Bending Ability of a Hinged Trisaccharide with the Assistance of a Sugar––Sugar Interaction
Authors: Yuasa Hideya , Izumi Takuhiro , Mitsuhashi Nobuyuki , Kajihara Yasuhiro , Hashimoto Hironobu 
Published: August 2005

AbstractHinged di‐ and trisaccharides incorporating 2,4‐diamino‐β‐D‐xylopyranoside as a hinge unit (Hin) were synthesized. Bridging of the diamino group of Hin by carbonylation or chelation to a metal ion results in a conformational change from 4C1 to 1C4, which in turn causes a bending of the oligosaccharides. In this study, the bending abilities of the hinged oligosaccharides were compared, in terms of the reactivities toward carbonylation and chelation. Di‐ or trisaccharides containing a 6‐O‐glycosylated mannopyranoside or galactopyranoside at their reducing ends had bending abilities similar to that of the Hin monosaccharide, probably because there were neither attractive nor repulsive interactions between the reducing and nonreducing ends. However, when Hin was attached at O2 of methyl mannopyranoside (ManαMe), the bending ability was dependent on the nonreducing sugar and the reaction conditions. Typically, a disaccharide—Hinβ(1,2)ManαMe—was difficult to bend under all the tested reaction conditions, and the bent population in the presence of ZnII was only 4 %. On the other hand, a trisaccharide—Manα(1,3)Hinβ(1,2)ManαMe—was bent immediately after the addition of ZnII or HgII, and the bent population reached 75 %, much larger than those of all the other hinged trisaccharides ever tested (<40 %). This excellent bending ability suggests an attractive interaction between the reducing and nonreducing ends. The extended conformation was recovered by the addition of triethylenetetramine, a metal ion chelator. Reversible, quick, and efficient bending of the hinged trisaccharide was thus achieved.
Anionic Organic Guests Incorporated in Zeolites: Adsorption and Reactivity of a Meisenheimer Complex in Faujasites
Authors: Herance José Raul , Concepción Patricia , Doménech Antonio , Bourdelande José Luis , Marquet Jordi , García Hermenegildo 
Published: August 2005

AbstractZeolites are suitable microporous hosts for positively charged organic species, but it is believed that they cannot adsorb organic anions. Pure Meisenheimer complex, derived from reduction of 2,4‐dinitroaniline with NaBH4, was adsorbed inside faujasite cavities. Evidence for the internal incorporation of this negatively charged reaction intermediate comes from 1) XPS elemental analysis as a function of the depth of penetration into the particle, 2) the remarkable blue shift in λmax of the Meisenheimer complex adsorbed on zeolite (ca. 470 nm) as compared to that in acetonitrile (580 nm) and 3) from the lack of reactivity with size‐excluded hydride‐acceptor reagents. Evidence is provided in support of an adsorption mechanism in which a neutral ion pair (alkali metal ion+Meisenheimer anion) is the actual species being adsorbed. In fact it appears that there is remarkable increase in the association constant for the ion‐pair complex within the zeolite cavities as compared to DMF solution. Although this mechanism of adsorption as an ion‐pair complex has precedents in the adsorption of some inorganic salts, what is novel is the notable increase in the stability and persistence of the Meisenheimer anion (a anionic reaction intermediate) as a result of zeolite inclusion. Adsorbed Meisenheimer complex exhibits much lower reactivity towards electron acceptors, oxygen, and water. Cyclic voltammetry of zeolite‐modified electrodes reveals for the Meisenheimer complex adsorbed on LiY a reversible redox peak that is not observed in solution and has been interpreted as arising from site isolation and stabilisation of the electrochemically generated species.