bluuebunny/crossref_metadata_2025_split huggingface dataset:
High glucose increases growth and collagen synthesis in cultured human tubulointerstitial cells
Authors: Jones S. C. , Saunders H. J. , Pollock C. A. 
Published: July 2002

Summary Aims Altered proximal tubular cell growth and interstitial fibrosis are features of diabetic nephropathy and correlate with disease progression. These observations are poorly understood, although it has been suggested that they are secondary to glomerular disease. The primary aim of this study was to assess the direct effects of high extracellular glucose concentrations on the human tubulointerstitium.Methods Primary cultures of human proximal tubule cells (PTCs) and cortical fibroblasts (CFs) were grown for 6 days in media containing either 6.1 mmol/l or 25 mmol/l glucose. Cell proliferation, thymidine uptake (a marker of DNA synthesis), protein content and collagen synthesis were measured.Results In PTCs, exposure to high glucose was associated with a 410 ± 108% increase in cell numbers (P < 0.001); 101 ± 24% increase in thymidine uptake per cell (P < 0.01) and a 39 ± 6% decease in protein content per cell (P < 0.05). Collagen synthesis was increased by 37 ± 11% (P < 0.05). In CFs, exposure to high glucose was associated with an 80 ± 25% increase in cell numbers (P < 0.05); 137 ± 50% increase in thymidine uptake per cell (P < 0.001), with protein content per cell unchanged. Collagen synthesis increased by 37 ± 13%; however, the difference was not significant (P = 0.07). There were no differences between control cells exposed to 6.1 mmol/l glucose or an osmotic control (6.1 mmol/l
d‐glucose + 18.9 mmol/l
l‐glucose).Conclusions Exposure of human PTCs and CFs to high extracellular glucose concentrations results directly in altered cell growth and collagen synthesis that is independent of haemodynamic, glomerular or vascular pathology.
Towards an understanding of the high death rate among young people with diabetes in Ukraine
Authors: Telishevka M. , Chenet L. , McKee M. 
Published: July 2002

SUMMARY Aims  Published rates of deaths attributed to diabetes mellitus among those aged under 50 have risen substantially in several former Soviet republics since the late 1980s. The reasons for this increase, and the situation facing patients with diabetes in these countries are poorly understood. The aim of this study was to describe the circumstances leading up to the death of individuals dying under the age of 50 years with mention of diabetes on their death certificate.Methods  Interviews with surviving relatives or neighbours, combining elements of verbal autopsy and confidential enquiry. For those who had lived in the city of Lviv a random sample was taken. For those in rural areas a purposive sample was used to ensure coverage of more and less remote areas.Results  Key informants were identified and agreed to be interviewed for 64 individuals out of a possible 79 with insulin‐treated diabetes identified from their death certificates. The main immediate causes of death were renal failure (69%), ischaemic heart disease (9%), ketoacidosis (6%) and hypoglycaemia (3%). Over a third of men, but no women, were reported to have been heavy drinkers. Informants described many difficulties in obtaining regular supplies of insulin and related supplies since 1990. Although insulin is officially available free of charge, most had retained supplies for use in an emergency. More than half had, at some time, purchased supplies. The large number of deaths from renal failure reflects the effective absence of renal replacement therapy for patients with diabetes.Conclusions  Individuals with diabetes in Ukraine face profound challenges involving access to necessary care. Their needs require significantly more attention from policy makers.
Changes in the lower displacement limit for motion with age
Authors: Wood Joanne M. , Bullimore Mark A. 
Published: July 2002

SummaryPrevious studies have alleged that the ability to perceive motion remains constant with age. We investigated the effect of age on minimum displacement thresholds using computer‐generated random dot stimuli in 91 healthy, visually normal subjects (age range 21–82 years). High and low contrast visual acuity and letter contrast sensitivity were also tested. We found that minimum displacement thresholds increased significantly at a rate of 0.07 log min arc per decade ( 17%). The relationship between age and performance was very similar for all visual tests.
Use of contact lenses by firefighters. Part 1: Questionnaire data
Authors: Owen Christopher G. , Margrain Thomas H. , Woodward E. Geoffrey 
Published: July 2002

SummaryThe use of contact lenses by firefighters is currently prohibited. However, many firefighters may benefit from this form of visual correction, without predisposing themselves to additional risk. Visual benefits gained by contact lens wear may increase a firefighter's safety. To determine if it is safe to allow firefighters to use contact lenses 29 were fitted with soft contact lenses and 21 with rigid gas permeable contact lenses. Questionnaires were completed prior to fitting, after 1, 4 and 10 months of contact lens wear. Both soft contact lens (SCL) wearers, and rigid gas permeable contact lens (RGPCL) wearers showed a statistically significant reduction in the frequency with which they experienced irritable foreign bodies and irritant fumes in the eyes, compared to not wearing contact lenses. Firefighters felt that their performance on the fireground had been improved by the use of contact lenses. SCL wearers also benefited from a reduction in the frequency with which they experienced watery eyes and ocular discomfort. There were significantly fewer problems encountered with SCL wearers than RGPCL wearers. The frequency with which firefighters experienced lenses falling out, lens displacement, watery eyes, ocular discomfort, and operational difficulties was significantly less for the SCL group than the RGPCL group. SCL appear to offer considerable benefits for firefighters with refractive error, but their use cannot be sanctioned without assessment of their effect on the ocular adnexa.
Evidence‐Based Assessment of Pregnancy Outcome After Sumatriptan Exposure
Authors: Fox Anthony W. , Chambers Christina D. , Anderson Philip O. , Diamond Merle L. , Spierings Egilius L.H. 
Published: July 2002

Objective.—Assessment of best available evidence for tolerability of sumatriptan after inadvertent exposure during pregnancy.Background.—Migraine's demography suggests that inadvertent exposure to acute therapies is likely during the earliest undiagnosed stages of pregnancy. The tolerability of such therapies under these conditions is not amenable to clinical trial for ethical reasons. In the United States, sumatriptan is currently labeled pregnancy category C (ie, not recommended for use during pregnancy unless the potential benefit justifies the potential risk to the fetus).Methods.—Three types of adverse events were studied: spontaneous abortion, fetal abnormality, and obstetric complications. Traditional evidence‐based criteria were used to assess a search‐protocol product of four clinical studies and two case reports.Results.—The single positive finding (“preterm delivery” without low birth weight) was in the smallest study; this study was retrospective and the finding was externally inconsistent with the other three larger studies, all of which were prospective. No study followed children for more than 4 years, which is the period needed to identify the maximum number of congenital anomalies. Rigorous teratological technique was generally not employed. Post hoc power calculations were used to provide parameters of the hazard detectable by these studies in aggregate.Conclusions.—Pregnancy categories B and C both seem feasible for sumatriptan. Within the limits of the examined studies, there is no evidence for any specific effect of sumatriptan on pregnancy outcome. Patients inadvertently exposed to sumatriptan during an early stage of pregnancy should be reassured by these data.
Ab initio molecular orbital study of the molecular and electronic structure of FeCH+2 and of the reaction mechanism of FeCH+2+H2
Authors: Musaev Djamaladdin G. , Morokuma Keiji 
Published: July 2002

Both complete active space self-consistent field (CASSCF) and internally contracted single and double configuration interaction from the CASSCF reference functions (MR-SDCI-CASSCF) methods have been used to study the molecular and electronic structures of FeCH+2, as well as the mechanism for the reaction FeCH+2+H2. Three quartet electronic states of FeCH+2 are very low-lying; the ground state is a nearly degenerate pair (4B2 and 4B1), with the 4A2 state only 1–2 kcal/mol higher in energy. The lowest doublet states are about 25–35 kcal/mol higher. The binding energy of FeCH+2(4B2), relative to the dissociation limit Fe+(6D,s1d6)+CH2(3B1), is estimated to be 68 kcal/mol. In the first step of reaction FeCH+2+H2, the reactants yield an ion-molecule complex, (H2)FeCH+2, stabilized by about 6 kcal/mol. Subsequently, the H–H bond is activated, leading to a four-center transition state with an energy barrier of about 24 and 14 kcal/mol for the ground 4A″ and excited 2A′ states of the reactants. This step is calculated to be the rate-determining for the entire reaction, and therefore the doublet excited state of FeCH+2 is expected to be more reactive than the ground state because of the lower barrier. The resultant HFeCH+3 complex is predicted to be a minimum at the CASSCF level, but at the highest MR-SDCI-CASSCF level this minimum disappears. Thus, following the H–H bond cleavage, an FeCH+4 ion-molecule complex is directly formed.
The ground state of the FeCH+4 complex is the sextet 6A2 state, which is stable relative to the ground state dissociation Fe+(6D,s1d6)+CH4 by 16 kcal/mol. The entire FeCH+2 hydrogenolysis reaction FeCH+2(4B2)+H2→Fe+(6D,s1d6)+CH4 (1) is estimated to be exothermic by 29 kcal/mol. The channels leading to formation of FeH++CH3 (2) and FeCH+3+H (3) are thermodynamically almost neutral. The reverse reaction Fe++CH4 for 6D, 4F or 2G states of Fe+ gives only one product, the ion-molecule complex FeCH+4 at moderate temperatures. An increase in the available kinetic energy for 6D and 4F states would make it possible to form dissociation products, FeH++CH3 and FeCH+3+H. Though the channel leading to FeCH+2+H2 is thermodynamically as easy as (2) and (3), a large barrier prevents it from taking place.
Expression and Characterization of Human Ecto‐ATPase and Chimeras with CD39 Ecto‐Apyrase
Authors: Hicks‐Berger Carrie A. , Kirley Terence L. 
Published: July 2002

AbstractHuman ecto‐ATPase (ecto‐nucleoside triphosphate d iphosphohydrolase 2 [eNTPDase2], also known as CD39L1) has been expressed and characterized in COS cells. It exhibits some unusual enzymology that is similar to a few members of this class of proteins but different from the majority of the family members. Hydrolysis of ATP by human ecto‐ATPase is nonlinear with time, and its activity is stimulated/stabilized by both the lectin concanavalin A and the chemical cross‐linking agent disuccinimidyl suberate. Like other members of the eNTPDase family, the human ecto‐ATPase is a tetramer, the activity of which depends on its glycosylation. Chimeras of this protein with human CD39 (eNTPDase1) were constructed to test the hypothesis that the N‐terminal half of these proteins regulates nucleotide specificity. The two chimeras generated demonstrated that the N‐terminal half of these proteins is crucial for determining the relative activities of the nucleoside diand triphosphatases. Chemical cross‐linking of the two chimeras suggests that disuccinimidyl suberate interacts with the C‐terminal half of ecto‐ATPase in a manner that results in an increase of activity for both the ecto‐ATPase and the ecto‐apyrase/ecto‐ATPase chimera.
Empirical evidence for the Birch and Swinnerton-Dyer conjectures for modular Jacobians of genus 2 curves
Authors: Flynn E. , Leprévost Franck , Schaefer Edward , Stein William , Stoll Michael , Wetherell Joseph 
Published: July 2002

This paper provides empirical evidence for the Birch and Swinnerton-Dyer conjectures for modular Jacobians of genus 2 curves. The second of these conjectures relates six quantities associated to a Jacobian over the rational numbers. One of these six quantities is the size of the Shafarevich-Tate group. Unable to compute that, we computed the five other quantities and solved for the last one. In all 32 cases, the result is very close to an integer that is a power of 2. In addition, this power of 2 agrees with the size of the 2-torsion of the Shafarevich-Tate group, which we could compute.
ProtEST: protein multiple sequence alignments from expressed
sequence tags
Authors: Cuff James A. , Birney Ewan , Clamp Michele E. , Barton Geoffrey J. 
Published: July 2002

Abstract
Motivation: An automatic sequence searching method (ProtEST) is described which constructs multiple protein sequence alignments from protein sequences and translated expressed sequence tags (ESTs). ProtEST is more effective than a simple TBLASTN search of the query against the EST database, as the sequences are automatically clustered, assembled, made non-redundant, checked for sequence errors, translated into protein and then aligned and displayed.
Results: A ProtEST search found a non-redundant, translated, error- and length-corrected EST sequence for &58% of sequences when single sequences from 1407 Pfam-A seed alignments were used as the probe. The average family size of the resulting alignments of translated EST sequences contained &10 sequences. In a cross-validated test of protein secondary structure prediction, alignments from the new procedure led to an improvement of 3.4% average Q3 prediction accuracy over single sequences.
Availability: The ProtEST method is available as an Internet World Wide Web service at http://barton.ebi.ac.uk/servers/protest.htmlThe Wise2 package for protein and genomic comparisons and the ProtESTWise script can be found at: http://www.sanger.ac.uk/Software/Wise2
Contact: geoff@ebi.ac.uk
Transgene overexpression of αB crystallin confers simultaneous protection against cardiomyocyte apoptosis and necrosis during myocardial ischemia and reperfusion
Authors: RAY PARTHA S. , MARTIN JODY L. , SWANSON ERIC A. , OTANI HAJIME , DILLMANN WOLFGANG H. , DAS DIPAK K 
Published: July 2002

ABSTRACTWe investigated whether enhanced expression of αB crystallin, a stress‐inducible molecular chaperone of the small heat shock family, can protect myocardial contractile apparatus against ischemia reperfusion (I/R) injury. Transgenic mice overexpressing αB crystallin were generated using the 0.76 kb rat αB crystallin cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. Southern analysis confirmed transgene integration and Northern and Western blotting characterized expression (3.1‐fold and 6.9‐fold elevations in myocardial mRNA and protein levels, respectively). Extent of functional recovery overa3hreperfusion period following a 20 min ischemic period in transgenic and wild‐type mouse hearts was assessed using an ex vivo work‐performing heart preparation. The transgenic group displayed significantly higher values of DP at R45 min (29.14±1.9mmHgvs. 17.6±0.7 mm Hg), R60 min (31.56±1.7mmHgvs. 17.8±0.8 mm Hg), and R75 min (32.5±2.2 mm Hg vs. 16.9±0.9 mm Hg), and of dLVP/dt at R45 min (1740.2±111.5 mm Hg.s−1 vs. 548.7±82.2 mm Hg.s−1) and R60 min (1199.8±104.6 mm Hg.s−1 vs. 466.9±61.1 mm Hg.s−1). The transgenic group also displayed development of less oxidative stress, decreased extent of infarction, and attenuated cardiomyocyte apoptotic cell death. Transgene overexpression of αB crystallin was therefore successful in diminishing the independent contributory effects of both necrosis and apoptosis on I/R‐induced cell death.—Ray, P. S., Martin, J. L., Swanson, E. A., Otani, H., Dillmann, W. H., Das, D. K. Transgene overexpression of aB crystallin confers simultaneous protection against cardiomyocyte apoptosis and necrosis during myocardial ischemia and reperfusion. FASEB J. 15, 393‐402 (2001)
Arginine‐140 and isoleucine‐141 determine the 17β‐estradiol‐binding specificity of the sex‐steroid‐binding protein (SBP, or SHBG) of human plasma
Authors: Petra Philip H. , Adman Elinor T. , Orr William R. , Woodcock Katherine T. , Groff Christine , Sui Li‐Ming 
Published: July 2002

AbstractArginine‐140 and isoleucine‐141 were identified as key determinants of 17β‐estradiol (E2) binding affinity of the sex‐steroid‐binding protein (SBP, or SHBG) of human plasma. Amino acid residues that differ between human and rabbit SBP sequences were replaced in the human protein and the products tested for lowered E2binding activity as are seen in the rabbit protein. Only mutants containing either R140K or I141L replacements display an E2 equilibrium dissociation constant (Kd) higher than the wild type, reaching a value of 30 nM when both were present. The 5α‐dihydrotestosterone (DHT) equilibrium dissociation constant of these mutants was unaffected. The quadruple mutant M107I/I138V/R140K/I141L yielded an E2 Kd of 65 nM, significantly closer to the 80 nM rabbit SBP E2 Kd value. Although mutants containing the M107I and I138V replacements in the absence of R140K and I141L had normal E2 Kds, the presence of the M107I replacement in the quadruple mutant was necessary to obtain an accurate E2 Kd value by competitive Scatchard analysis. Molecular modeling using coordinates for the recently determined N‐terminal domain of human SBP revealed a significant shift of the F56 phenyl ring away from ring A of E2 in mutant models containing the R140K and I141L replacements. We conclude that R140 and I141 are required for sustaining the right proximity of the phenyl ring of F56 to ring A of 17β‐estradiol, thus optimizing the E2‐binding affinity of human SBP.
Substitution of conserved methionines by leucines in chloroplast small heat shock protein results in loss of redox‐response but retained chaperone‐like activity
Authors: Gustavsson Niklas , Kokke Bas P.A. , Anzelius Björn , Boelens Wilbert C. , Sundby Cecilia 
Published: July 2002

AbstractDuring evolution of land plants, a specific motif occurred in the N‐terminal domain of the chloroplast‐localized small heat shock protein, Hsp21: a sequence with highly conserved methionines, which is predicted to form an amphipathic α‐helix with the methionines situated along one side. The functional role of these conserved methionines is not understood. We have found previously that treatment, which causes methionine sulfoxidation in Hsp21, also leads to structural changes and loss of chaperone‐like activity. Here, mutants of Arabidopsis thaliana Hsp21 protein were created by site‐directed mutagenesis, whereby conserved methionines were substituted by oxidation‐resistant leucines. Mutants lacking the only cysteine in Hsp21 were also created. Protein analyses by nondenaturing electrophoresis, size exclusion chromatography, and circular dichroism proved that sulfoxidation of the four highly conserved methionines (M49, M52, M55, and M59) is responsible for the oxidation‐induced conformational changes in the Hsp21 oligomer. In contrast, the chaperone‐like activity was not ultimately dependent on the methionines, because it was retained after methionine‐to‐leucine substitution. The functional role of the conserved methionines in Hsp21 may be to offer a possibility for redox control of chaperone‐like activity and oligomeric structure dynamics.
Site‐directed mutations of human hemoglobin at residue 35β: A residue at the intersection of the α1β1, α1β2, and α1α2 interfaces
Authors: Kavanaugh Jeffrey S. , Weydert Jamie A. , Rogers Paul H. , Arnone Arthur , Hui Hilda L. , Wierzba Anita M. , Kwiatkowski Laura D. , Paily Paul , Noble Robert W. , Bruno Stefano , Mozzarelli Andrea 
Published: July 2002

AbstractBecause Tyr35β is located at the convergence of the α1β1, α1β2, and α1α2 interfaces in deoxyhemoglobin, it can be argued that mutations at this position may result in large changes in the functional properties of hemoglobin. However, only small mutation‐induced changes in functional and structural properties are found for the recombinant hemoglobins βY35F and βY35A. Oxygen equilibrium‐binding studies in solution, which measure the overall oxygen affinity (the p50) and the overall cooperativity (the Hill coefficient) of a hemoglobin solution, show that removing the phenolic hydroxyl group of Tyr35β results in small decreases in oxygen affinity and cooperativity. In contrast, removing the entire phenolic ring results in a fourfold increase in oxygen affinity and no significant change in cooperativity. The kinetics of carbon monoxide (CO) combination in solution and the oxygen‐binding properties of these variants in deoxy crystals, which measure the oxygen affinity and cooperativity of just the T quaternary structure, show that the ligand affinity of the T quaternary structure decreases in βY35F and increases in βY35A. The kinetics of CO rebinding following flash photolysis, which provides a measure of the dissociation of the liganded hemoglobin tetramer, indicates that the stability of the liganded hemoglobin tetramer is not altered in βY35F or βY35A. X‐ray crystal structures of deoxy βY35F and βY35A are highly isomorphous with the structure of wild‐type deoxyhemoglobin. The βY35F mutation repositions the carboxyl group of Asp126α1 so that it may form a more favorable interaction with the guanidinium group of Arg141α2. The βY35A mutation results in increased mobility of the Arg141α side chain, implying that the interactions between Asp126α1 and Arg141α2 are weakened. Therefore, the changes in the functional properties of these 35β mutants appear to correlate with subtle structural differences at the C terminus of the α‐subunit.
Targeted Delivery of Apoptotic Cell‐Derived Nanovesicles prevents Cardiac Remodeling and Attenuates Cardiac Function Exacerbation
Authors: Lee Ju‐Ro , Sim Woo‐Sup , Park Hun‐Jun , Park Bong‐Woo , Joung Yoon Ki 
Published: January 2023

AbstractThe modulation of inflammatory responses plays an important role in the pathobiology of cardiac failure. In a natural healing process, the ingestion of apoptotic cells and their apoptotic bodies by macrophages in a focal lesion result in resolution of inflammation and regeneration. However, therapeutic strategies to enhance this natural healing process using apoptotic cell‐derived biomaterials have not yet been established. In this study, apoptotic bodies‐mimetic nanovesicles derived from apoptotic fibroblasts (ApoNVs) conjugated with dextran and ischemic cardiac homing peptide (CHP) (ApoNV‐DCs) for ischemia‐reperfusion (IR)‐injured heart treatment are developed. Intravenously injected ApoNV‐DCs actively targeted the ischemic myocardium via conjugation with CHP, and are selectively phagocytosed by macrophages in an infarcted myocardium via conjugation with dextran. ApoNV‐DCs polarized macrophages from the M1 to M2 phenotype, resulting in the attenuation of inflammation. Four weeks after injection, ApoNV‐DCs attenuated cardiac remodeling, preserved blood vessels, and prevented cardiac function exacerbation in IR‐injured hearts. Taken together, the findings may open a new avenue for immunomodulation using targeted delivery of anti‐inflammatory nanovesicles that can be universally applied for various inflammatory diseases.