bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxygen radical-induced natural killer cell dysfunction: role of myeloperoxidase and regulation by serotonin
Authors: Betten Åsa , Dahlgren Claes , Mellqvist Ulf-Henrik , Hermodsson Svante , Hellstrand Kristoffer 
Published: March 2004

AbstractNatural killer (NK) cells are functionally suppressed and induced to apoptosis by reactive oxygen species (ROS) produced by mononuclear phagocytes (MPs). These inhibitory events are reversed by the biogenic amine serotonin. MPs generate hydrogen peroxide (H2O2), which is processed further by myeloperoxidase (MPO) to even more toxic compounds. Earlier studies suggest that serotonin scavenges MP-derived oxygen radicals generated by the MPO-H2O2 system. These findings led us to explore the capability of MPO-deficient MPs to induce NK cell dysfunction. We show that MPs recovered from subjects with MPO deficiency trigger inhibition of NK cells. In addition, MPs recovered from healthy subjects conveyed suppression of NK cells in the presence of the MPO inhibitor ceruloplasmin. We conclude that ROS-dependent inhibition of NK cell function is unrestricted by the availability of MPO-derived oxygen radicals and that the protecting properties of serotonin may operate in the absence of functional MPO. Our data suggest a complex mechanism of MP-induced NK cell inhibition, which comprises the generation of interchangeable oxygen radicals.
Morphine-induced macrophage apoptosis: oxidative stress and strategies for modulation
Authors: Bhat Rajani S , Bhaskaran Madhu , Mongia Anil , Hitosugi Naoko , Singhal Pravin C 
Published: March 2004

AbstractOccurrence of macrophage apoptosis has been implicated for the altered immune function found in an opiate milieu. In the present study, we evaluated the role of oxidative stress in morphine-induced macrophage apoptosis. Morphine promoted the apoptosis of macrophages. This effect of morphine was associated with the production of superoxide and nitric oxide (NO). Antioxidants provided protection against morphine-induced macrophage injury. In addition, diphenyleneiodonium chloride, an inhibitor of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, attenuated the proapoptotic effect of morphine. Antitransforming growth factor-β (anti-TGF-β) antibody and propranolol (an inhibitor of the phospholipase D pathway) inhibited morphine-induced superoxide generation as well as apoptosis. N′-Tetraacetic acid tetra (acetoxymethyl) ester, a calcium-chelating agent, inhibited morphine-induced apoptosis, whereas thapsigargin (a calcium agonist) stimulated macrophage apoptosis under basal as well as morphine-stimulated states. These studies suggest that morphine-induced macrophage apoptosis is mediated through downstream signaling involving TGF-β and NO production. Moreover, there is NADPH oxidation activation involving phospholipase D and Ca2+, leading to the generation of superoxide. In in vivo studies, administration of N-acetyl cysteine and preinduction of heme oxygenase activity and epoetin α prevented morphine-induced peritoneal macrophage apoptosis, thus further confirming the role of oxidative stress in morphine-induced macrophage apoptosis.
Abbreviated Course of Radiation Therapy in Older Patients With Glioblastoma Multiforme: A Prospective Randomized Clinical Trial
Authors: Roa W. , Brasher P.M.A. , Bauman G. , Anthes M. , Bruera E. , Chan A. , Fisher B. , Fulton D. , Gulavita S. , Hao C. , Husain S. , Murtha A. , Petruk K. , Stewart D. , Tai P. , Urtasun R. , Cairncross J.G. , Forsyth P. 
Published: March 2004

Purpose To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). Patients and Methods One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). Results All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P = .57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, −13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P = .63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (χ2 test, P = .02). Conclusion There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.
Glucose Homeostasis and Tissue Transcript Content of Insulin Signaling Intermediates in Four Inbred Strains of Mice: C57BL/6, C57BLKS/6, DBA/2, and 129X1
Authors: Goren H. Joseph , Kulkarni Rohit N. , Kahn C. Ronald 
Published: March 2004

Abstract
Transgenic mice phenotypes generally depend on the background strains used in their creation. To examine the effects of genetic background on insulin signaling, we analyzed glucose homeostasis in four inbred strains of mice [C57BL/6 (B6), C57BLKS/6 (KLS), DBA/2 (DBA), and 129X1] and quantitated mRNA content of insulin receptor (IR) and its substrates in insulin-responsive tissues. At 2 months, the male B6 mouse is the least glucose-tolerant despite exhibiting similar insulin sensitivity and first-phase insulin secretion as the other strains. The 129X1 male mouse islet contains less insulin and exhibits a higher threshold for glucose-stimulated first-phase insulin secretion than the other strains. Female mice generally manifest better glucose tolerance than males, which is likely due to greater insulin sensitivity in liver and adipose tissue, a robust first-phase insulin secretion in B6 and KLS females, and improved insulin sensitivity in muscle in DBA and 129X1 females. At 6 months, although males exhibit improved first-phase insulin secretion, their physiology was relatively unchanged, whereas female B6 and KLS mice became less insulin sensitive. Gene expression of insulin signaling intermediates in insulin-responsive tissues was generally not strain dependent with the cell content of IR mRNA being highest. IR substrate (IRS)-1 and IRS-2 mRNA are ubiquitously expressed and IRS-3 and IRS-4 mRNA were detected in significant amounts in fat and brain tissues, respectively. These data indicate strain-, gender-, and age-dependent tissue sensitivity to insulin that is generally not associated with transcript content of IR or its substrates and should be taken into consideration during phenotypic characterization of transgenic mice.
Minireview: Characterization of Influence of Central Nociceptin/Orphanin FQ on Consummatory Behavior
Authors: Olszewski Pawel K. , Levine Allen S. 
Published: March 2004

Abstract
Nociceptin/orphanin FQ (N/OFQ), a peptide closely related to dynorphin A, is the endogenous agonist of the NOP receptor that moderately increases food intake under various conditions. Its orexigenic properties are mediated by the brain circuitry. In the present review, we focus on discussing the nature of hyperphagic effects of N/OFQ with special emphasis on its function within feeding-related neural networks. Although some of N/OFQ’s orexigenic effects resemble those induced by opioids, reward-dependent feeding appears to be affected in a different manner by agonists of the NOP and classical opioid receptors. Also, data suggest that N/OFQ may not only promote feeding initiation, but rather its role may be to inhibit signaling responsible for inhibition of consummatory behavior. Central systems involved in termination of feeding that seem to be influenced by N/OFQ encompass oxytocin, α-MSH, and CRH.
Expression of Progesterone Receptors A and B in the Mouse Ovary during the Estrous Cycle
Authors: Gava Natalie , Clarke Christine L. , Byth Karen , Arnett-Mansfield Rebecca L. , deFazio Anna 
Published: March 2004

AbstractProgesterone plays a central role in the regulation of ovarian function. The progesterone receptor (PR) has been shown to be essential for ovulation because mice lacking PR fail to ovulate and are infertile. PR is expressed as two isoforms, PRA and PRB, which have been shown to have different functional activities. In this study, we investigated the cellular distribution of PRA and PRB in the ovaries and oviducts of cycling mice using immunohistochemistry with isoform-specific monoclonal antibodies. In the ovary, on the evening of proestrus before ovulation, both the granulosa and theca cells of the preovulatory follicles expressed both PR isoforms. PRA and PRB staining was also observed in the theca cells of preantral and antral follicles, whereas only PRB was observed in the granulosa cells of primary, preantral, and antral follicles and in the corpus luteum. In the oviduct, PRA was the predominant isoform observed, expressed in both the epithelial and stromal cells, whereas PRB was only detected in the epithelial cells. The differences in PRA and PRB localization in the ovary and oviduct may reflect diverse functions for PRA and PRB in reproductive tissues and may have important implications in understanding the mechanisms of progesterone action.
Temperature Dependence of the Structure of Alkyl Monolayers on Si(111) Surface via Si–C Bond by ATR-FT-IR Spectroscopy
Authors: Yamada Ryo , Ara Masato , Tada Hirokazu 
Published: March 2004

Abstract
The temperature dependence of C–H stretching modes of alkyl monolayer formed on Si(111) surface was investigated by an attenuated total reflection Fourier transform infrared spectroscopy from room temperature up to 540 K. Continuous disordering of the monolayer was indicated from the gradual peak shifts toward higher frequency in C–H stretch modes upon heating. The irreversible conformational disorder was introduced in the monolayer above 440 K.
Iodo-cyclization of N-Homoallyl Thioamides Leading to 2,4-Diaryl-5,6-dihydro-4H-1,3-thiazines
Authors: Murai Toshiaki , Niwa Hisayuki , Kimura Tsutomu , Shibahara Fumitoshi 
Published: March 2004

Abstract
Iodo-cyclization of N-homoallyl thioamides was carried out in the presence of Et3N to form 2,4-diaryl-5,6-dihydro-4H-1,3-thiazines in good to high yields. The reaction of thioamides bearing 1-naphthyl or 2-methoxyphenyl group at the carbon atom adjacent to the nitrogen atom showed high diastereoselectivity. The relative stereochemistry was confirmed by X-ray molecular structure analyses. The obtained thiazines were converted to 6-alkylidene-1,3-thiazines by treating with pyrrolidine.
Dexmedetomidine Overdose in the Perioperative Setting
Authors: Jorden Victor SB , Pousman Robert M , Sanford Mary M , Thorborg Per AJ , Hutchens Michael P 
Published: March 2004

OBJECTIVE To report 3 cases of accidental dexmedetomidine overdose in the perioperative setting and review the pathophysiology of α2-agonist overdose. CASE SUMMARIES Three patients accidentally received overdoses of dexmedetomidine, one intraoperatively (192 μg over 20 min) and 2 postoperatively (4 and 2 rather than 0.4 and 0.2 μg/kg/h; 0.5 μg/kg/min rather than 0.5 μg/kg/h). Hemodynamic parameters remained stable for all 3 patients. The most notable sign was oversedation diagnosed either clinically or using a bispectral index monitor; Naranjo criteria suggest possible or probable association of the reactions with dexmedetomidine. In all 3 cases, oversedation resolved within one hour of drug discontinuation. There were no other sequelae, and the remainder of each patient's hospital course was unremarkable. DISCUSSION As of this writing, dexmedetomidine dosing in excess of the label recommendation has been reported, but accidental dexmedetomidine overdose in clinical practice has not been described. Excessive levels of sedation were the only significant finding in all 3 patients. Dexmedetomidine's short redistribution half-life of 6 minutes should lead to rapid resolution of oversedation induced by overdoses if the overall duration of infusion is short (≤8 h). While the patients reported here were hemodynamically stable, dexmedetomidine may engender significant hemodynamic changes either because of sympatholysis at normal doses or vasoconstriction at higher than recommended doses. The absence of a significant hypertensive response to high dexmedetomidine concentrations suggests that dexmedetomidine-induced hypertension may be multifactorial, not simply related to plasma drug concentrations. CONCLUSIONS Practitioners presented with dexmedetomidine overdose should be prepared to manage oversedation. While hemodynamic alterations may be seen with dexmedetomidine use, hypertension from high dexmedetomidine plasma concentrations is not a consistent response. Practitioners using dexmedetomidine should carefully note that dosing for this agent is described by the manufacturer in μg/kg/h, not μg/kg/min.
Intermittent Visceral Edema Induced by Long-Term Enalapril Administration
Authors: Orr Katherine K , Myers James R 
Published: March 2004

OBJECTIVE To describe a case of intermittent visceral angioedema associated with long-term enalapril use. CASE SUMMARY A 72-year-old white woman developed severe abdominal pain as a result of visceral angioedema associated with long-term enalapril therapy. She had been taking enalapril 20 mg/day for 9 years prior to the first reported episodes of abdominal pain. DISCUSSION Visceral angioedema associated with angiotensin-converting enzyme (ACE) inhibitors is a documented adverse effect. However, onset of symptoms has never been reported after 9 years of use. Not until 2 years after initial presentation were the symptoms correlated to enalapril administration. Since discontinuation of enalapril, the patient has not reported any symptoms for >2 years. An objective causality assessment categorized this adverse drug event as a result of enalapril as possible. CONCLUSIONS Development of angioedema from ACE inhibitors occurs in <1% of the population. Limited case reports have identified intermittent visceral angioedema from ACE inhibitors. However, it is important to recognize that this adverse effect can also occur in patients who have been treated with ACE inhibitor therapy for several years.
Synthetic Peptide Studies on the Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Glycoprotein: Perspective for SARS Vaccine Development
Authors: Choy Wai-Yan , Lin Shu-Guang , Chan Paul Kay-Sheung , Tam John Siu-Lun , Lo Y M Dennis , Chu Ida Miu-Ting , Tsai Sau-Na , Zhong Ming-Qi , Fung Kwok-Pui , Waye Mary Miu-Yee , Tsui Stephen Kwok-Wing , Ng Kai-On , Shan Zhi-Xin , Yang Min , Wu Yi-Long , Lin Zhan-Yi , Ngai Sai-Ming 
Published: March 2004

Abstract
Background: The S (spike) protein of the etiologic coronavirus (CoV) agent of severe acute respiratory syndrome (SARS) plays a central role in mediating viral infection via receptor binding and membrane fusion between the virion and the host cell. We focused on using synthetic peptides for developing antibodies against SARS-CoV, which aimed to block viral invasion by eliciting an immune response specific to the native SARS-CoV S protein.
Methods: Six peptide sequences corresponding to the surface regions of SARS-CoV S protein were designed and investigated by use of combined bioinformatics and structural analysis. These synthetic peptides were used to immunize both rabbits and monkeys. Antisera collected 1 week after the second immunization were analyzed by ELISA and tested for antibody specificity against SARS-CoV by immunofluorescent confocal microscopy.
Results: Four of our six synthetic peptides (S2, S3, S5, and S6) elicited SARS-CoV-specific antibodies, of which S5 (residues 788–820) and S6 (residues 1002–1030) exhibited immunogenic responses similar to those found in a parallel investigation using truncated recombinant protein analogs of the SARS-CoV S protein. This suggested that our S5 and S6 peptides may represent two minimum biologically active sequences of the immunogenic regions of the SARS-CoV S protein.
Conclusions: Synthetic peptides can elicit specific antibodies to SARS-CoV. The study provides insights for the future development of SARS vaccine via the synthetic-peptide-based approach.
Free radical graft copolymerization of poly(n‐butyl methacrylate) and poly(butyl acrylate) onto chlorinated rubber: Characterization and mechanical properties
Authors: Ahmed Shanaz , Radhakrishnan N. , Srinivasan K. S. V. , Sanjeevi R. 
Published: March 2004

AbstractGraft copolymerization of n‐butyl methacrylate and butyl acrylate onto chlorinated rubber was carried out in solution medium (xylene) using benzoyl peroxide as initiator. The chlorinated rubber‐g‐(n‐butyl methacrylate‐co‐butyl acrylate) (CR‐g‐nBMA‐co‐BA) was isolated from the copolymerization mixture by extracting with isopropyl ether. Infrared (FT‐IR) spectra, proton nuclear magnetic resonance (1H NMR) and thermogravimetric analysis of the graft copolymer showed the occurrence of grafting. Percent grafting and grafting efficiency calculated under different experimental conditions are discussed. The mechanical properties of the grafted CR films were studied under different strain rates. © 2004 Wiley Periodicals, Inc. Adv Polym Techn 23: 103–110, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20003
The Analysis of the Seasonal, Spatial, and Compositional Distribution of Humic Substances in a Subtropical Shallow Lake
Authors: Mazzuoli Stefania , Loiselle Steven , Hull Vincent , Bracchini Luca , Rossi Claudio 
Published: March 2004

AbstractThe spatial and temporal distribution of humic substances in aquatic ecosystems can have important effects on ecosystem productivity, negatively impacting primary productivity while positively impacting secondary productivity. In the present investigation, a large shallow lake ecosystem was studied to determine the spatial and seasonal variation of the composition and concentration of humic substances. Concentrations of total dissolved organic matter, humic acid, and fulvic acid were found to display significant spatial distributions (1.3…13.5 mg/L, DOM; 0.1…5.4 mg/L, HA). The distribution is described by using mapping techniques and the analysis of the spatial distribution of the lake. An analysis of the seasonal variations also indicated the dependence of the occurrence of these compounds on meteorological and hydrological conditions.To identify the potential sources of these organic materials, an analysis was made of the ratio of humic and fulvic acid fractions and total DOM. It was found that areas of high DOM concentration coincided with the areas of highest HA percentage of total DOM. Furthermore using the ratio of the normalised concentrations of HA, FA, and residual DOM (< 5000 g/mol) it was found that areas dominated by each are spatially distinct. This confirms the hypothesis that in these shallow lakes, photodegradation and bacterioplankton activity will create a residence time dependent zonation of each component of the total DOM.
Optimization of the Sampling Technique for the Determination of Dissolved Hydrogen in Groundwater
Authors: Heimann Axel , Marczinek Silke , Kloosb Karin , Peiffer Stefan 
Published: March 2004

AbstractIn this study a field‐sampling technique for dissolved hydrogen (H2) in groundwater will be presented which allows the transport of gaseous samples into the laboratory for further analysis. The method consists of transferring the headspace trapped in a gas‐sampling bulb which is continuously purged by groundwater into previously evacuated vials using a gas‐tight syringe. Three transfer steps with preceding evacuation of the vial led to a H2‐recovery of 100 % in laboratory experiments. The method has been applied to determine H2 concentrations in an aquifer contaminated with chlorinated solvents.Tests concerning the effect of different pumping techniques on H2 concentrations revealed that most reliable values were obtained with a bladder pump, while an electrically driven submersible pump generated considerable amounts of hydrogen due to electrochemical interactions with the sampled water. Concentrations of dissolved hydrogen in field and laboratory samples were about two orders of magnitude higher when sampling was performed with the electrically driven submersible pump compared to sampling with the bladder pump and a peristaltic pump.Lab experiments with a Plexiglas reservoir to produce H2‐enriched water were used to study the effect of two tubing materials (PVC, polyamide) on H2 losses. PVC tubing turned out to allow transfer of H2‐enriched water over 25 m without significant losses, while PA‐tubing was not suitable for sampling of H2.
Peroxisome biogenesis disorders with prolonged survival: Phenotypic expression in a cohort of 31 patients
Authors: Poll‐The Bwee Tien , Gootjes Jeannette , Duran Marinus , de Klerk Johannis B.C. , Maillette de Buy Wenniger‐Prick Liesbeth J. , Admiraal Ronald J.C. , Waterham Hans R. , Wanders Ronald J.A. , Barth Peter G. 
Published: March 2004

AbstractThe peroxisome biogenesis disorders (PBDs) with generalized peroxisomal dysfunction include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). There is clinical, biochemical, and genetic overlap among the three phenotypes, also known as Zellweger spectrum disorders. Clinical distinctions between the phenotypes are not sharply defined. Only limited sources are available to serve as a background for prognosis in PBD, especially in case of prolonged survival. We delineated the natural history of 31 PBD patients (age 1.2–24 years) through systematic clinical and biochemical investigations. We excluded classical ZS from our study, and included all patients with a biochemically confirmed generalized peroxisomal disorder over 1 year of age, irrespective of the previously diagnosed phenotype. The initial clinical suspicion, age at diagnosis, growth, development, neurological symptoms, organ involvements, and survival are summarized. Common to all patients were cognitive and motor dysfunction, retinopathy, sensorineural hearing impairment, and hepatic involvement. Many patients showed postnatal growth failure, 10 patients displayed hyperoxaluria of whom 4 had renal stones. Motor skills ranged from sitting with support to normal gait. Speech development ranged from non‐verbal expression to grammatical speech and comprehensive reading. The neurodevelopmental course was variable with stable course, rapid decline with leukodystrophy, spinocerebellar syndrome, and slow decline over a wide range of faculties as outcome profiles. At the molecular level, 21 patients had mutations in the PEX1 gene. The two most common PEX1 mutations were the G843D (c.2528G→A) missense and the c.2097insT frameshift mutation. Patients having the G843D/G843D or the G843D/c.2097insT genotypes were compared. Patients homozygous for G843D generally had a better developmental outcome. However, one patient who was homozygous for the “mild” G843D mutation had an early lethal disease, whereas two other patients had a phenotype overlapping with the G843D/c.2097insT group. This indicates that next to the PEX1 genotype other yet unknown factors determine the ultimate phenotype. © 2004 Wiley‐Liss, Inc.