bluuebunny/crossref_metadata_2025 huggingface dataset:
MAPK and JNK transduction pathways can phosphorylate Sp1 to activate the uPA minimal promoter element and endogenous gene transcription
Authors: Benasciutti Elisa , Pagès Gilles , Kenzior Olga , Folk William , Blasi Francesco , Crippa Massimo P.
Published: March 2004

Two upstream regions of the human urokinase (uPA) gene regulate its transcription: the minimal promoter (MP) and the enhancer element. The activity of the minimal promoter is essential for basal uPA transcription in prostate adenocarcinoma PC3 cells. Binding of a phosphorylated Sp1 transcription factor is, in turn, essential for the activity of the MP. Here we report that the Jun kinase (JNK) pathway is required for the basal activity of the MP and for the expression of the endogenous uPA gene in PC3 cells and for activated transcription in LNCaP cells. On the other hand, the p42/p44 mitogen-activated protein kinase (MAPK) pathway activates uPA gene expression through Sp1 phosphorylation in HeLa, LNCaP, and CCL39-derivative cells that do not typically express uPA in basal conditions. In HeLa cells the dominant-negative form of JNK interferes with the p42/p44 MAPK activation of the uPA-MP. The results suggest that the stress-activated protein kinase (SAPK)/JNK pathway plays an important role in the phosphorylation of Sp1, which, in turn, leads to basal or activated transcription from the uPA-MP element.
Yolk sac–derived primitive erythroblasts enucleate during mammalian embryogenesis
Authors: Kingsley Paul D. , Malik Jeffrey , Fantauzzo Katherine A. , Palis James
Published: March 2004

The enucleated definitive erythrocytes of mammals are unique in the animal kingdom. The observation that yolk sac–derived primitive erythroid cells in mammals circulate as nucleated cells has led to the conjecture that they are related to the red cells of fish, amphibians, and birds that remain nucleated throughout their life span. In mice, primitive red cells express both embryonic and adult hemoglobins, whereas definitive erythroblasts accumulate only adult hemoglobins. We investigated the terminal differentiation of murine primitive red cells with use of antibodies raised to embryonic βH1-globin. Primitive erythroblasts progressively enucleate between embryonic days 12.5 and 16.5, generating mature primitive erythrocytes that are similar in size to their nucleated counterparts. These enucleated primitive erythrocytes circulate as late as 5 days after birth. The enucleation of primitive red cells in the mouse embryo has not previously been well recognized because it coincides with the emergence of exponentially expanding numbers of definitive erythrocytes from the fetal liver. Our studies establish a new paradigm in the understanding of primitive erythropoiesis and support the concept that primitive erythropoiesis in mice shares many similarities with definitive erythropoiesis of mammals.
GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal–induced apoptosis
Authors: Asselin-Labat Marie-Liesse , David Muriel , Biola-Vidamment Armelle , Lecoeuche Damiana , Zennaro Maria-Christina , Bertoglio Jacques , Pallardy Marc
Published: March 2004

Interleukin-2 (IL-2) withdrawal is a physiologic process inducing cell death in activated T lymphocytes. Glucocorticoid-induced leucine zipper (GILZ) has recently been identified as a protein modulating T-cell receptor activation by repressing various signaling pathways. We report here that IL-2 deprivation leads to expression of GILZ in T lymphocytes. We then characterized the human gilz promoter and showed that FoxO3 (Forkhead box class O3) binding to the Forkhead responsive elements identified in the promoter is necessary for induction of gilz expression upon IL-2 withdrawal. To assess the functional consequences of this induction, we used 2 strategies, GILZ overexpression and GILZ silencing in murine IL-2–dependent CTLL-2 cells. GILZ overexpression protects CTLL-2 cells from IL-2 withdrawal–induced apoptosis, whereas cell death is accelerated in cells unable to express GILZ. Concomitantly, the expression of Bim is inhibited in GILZ-overexpressing cells and enhanced when GILZ expression is impaired. Furthermore, GILZ inhibits FoxO3 transcriptional activity that leads to inhibition of Bim expression but also to down-regulation of GILZ itself. Therefore, GILZ is a transiently expressed protein induced upon IL-2 withdrawal that protects T cells from the onset of apoptosis.
Visceral Obesity without Insulin Resistance in Late-Onset Obesity Rats
Authors: Bains Randip K. , Wells Sara E. , Flavell Dave M. , Fairhall Keith M. , Strom Molly , Le Tissier Paul , Robinson Iain C. A. F.
Published: March 2004

We describe a line of transgenic rats in which the males develop a unique autosomal dominant, late-onset obesity (LOB) phenotype. LOB males gradually accumulate fat specifically in visceral, but not peripheral, fat depots despite a normal intake of a low fat diet. LOB females normally develop only mild obesity with advanced age. However, the phenotype can be induced rapidly in young females by ovariectomy and prevented by estrogen replacement. LOB males are highly sensitive to dietary fat. Young, nonobese LOB males gain more weight on a 30% fat diet and lose more weight when treated with the lipase inhibitor, Orlistat, than their nontransgenic littermates. Remarkably, despite severe visceral obesity, LOB rats have normal fasting blood glucose, insulin, and corticosterone; show normal or increased insulin sensitivity in glucose and insulin tolerance tests; have increased plasma adiponectin levels; and display a heightened response to treatment with rosiglitazone. Their visceral adiposity reflects a specific increase in visceral adipocyte number, not size. Analysis of the transgene in LOB rats revealed a deletion in the gene encoding the S26 subunit of the mitochondrial ribosome that results in the production of a truncated protein, which we show to be imported into mitochondria. However, the transgene integrant is complex, so whether this is the sole molecular disruption underlying this phenotype remains to be established. Nevertheless, LOB rats provide a valuable new model of late-onset, male-preponderant, visceral-specific obesity, clearly dissociated from insulin resistance.
Saw Palmetto Extract Suppresses Insulin-Like Growth Factor-I Signaling and Induces Stress-Activated Protein Kinase/c-Jun N-Terminal Kinase Phosphorylation in Human Prostate Epithelial Cells
Authors: Wadsworth Teri L. , Carroll Julie M. , Mallinson Rebecca A. , Roberts Charles T. , Roselli Charles E.
Published: March 2004

A common alternative therapy for benign prostatic hyperplasia (BPH) is the extract from the fruit of saw palmetto (SPE). BPH is caused by nonmalignant growth of epithelial and stromal elements of the prostate. IGF action is important for prostate growth and development, and changes in the IGF system have been documented in BPH tissues. The main signaling pathways activated by the binding of IGF-I to the IGF-I receptor (IGF-IR) are the ERK arm of the MAPK cascade and the phosphoinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt) cascade. We tested the hypothesis that SPE suppresses growth and induces apoptosis in the P69 prostate epithelial cell line by inhibiting IGF-I signaling. Treatment with 150 μg/ml SPE for 24 h decreased IGF-I-induced proliferation of P69 cells and induced cleavage of the enzyme poly(ADP-ribose)polymerase (PARP), an index of apoptosis. Treatment of serum-starved P69 cells with 150 μg/ml SPE for 6 h reduced IGF-I-induced phosphorylation of Akt (assessed by Western blot) and Akt activity (assessed by an Akt kinase assay). Western blot analysis showed that SPE reduced IGF-I-induced phosphorylation of the adapter protein insulin receptor substrate-1 and decreased downstream effects of Akt activation, including increased cyclin D1 levels and phosphorylation of glycogen synthase kinase-3 and p70s6k. There was no effect on IGF-I-induced phosphorylation of MAPK, IGF-IR, or Shc. Treatment of starved cells with SPE alone induced phosphorylation the proapoptotic protein JNK. SPE treatment may relieve symptoms of BPH, in part, by inhibiting specific components of the IGF-I signaling pathway and inducing JNK activation, thus mediating antiproliferative and proapoptotic effects on prostate epithelia.
Evidence for an Interaction between CB1 Cannabinoid and Melanocortin MCR-4 Receptors in Regulating Food Intake
Authors: Verty A. N. A. , McFarlane J. R. , McGregor I. S. , Mallet P. E.
Published: March 2004

Melanocortin receptor 4 (MCR4) and CB1 cannabinoid receptors independently modulate food intake. Although an interaction between the cannabinoid and melanocortin systems has been found in recovery from hemorrhagic shock, the interaction between these systems in modulating food intake has not yet been examined. The present study had two primary purposes: 1) to examine whether the cannabinoid and melanocortin systems act independently or synergistically in suppressing food intake; and 2) to determine the relative position of the CB1 receptors in the chain of control of food intake in relation to the melanocortin system. Rats were habituated to the test environment and injection procedure and then received intracerebroventicular injections of various combinations of the MCR4 receptor antagonist JKC-363, the CB1 receptor agonist Δ9-tetrahydrocannabinol, the MCR4 receptor agonist α-MSH, or the cannabinoid CB1 receptor antagonist SR 141716. Food intake and locomotor activity were then recorded for 120 min. When administrated alone, SR 141716 and α-MSH dose-dependently attenuated baseline feeding, whereas sub-anorectic doses of SR 141716 and α-MSH synergistically attenuated baseline feeding when combined. Δ9-Tetrahydrocannabinol-induced feeding was not blocked by α-MSH, whereas SR 141716 dose-dependently attenuated JKC-363-induced feeding. Locomotor activity was not significantly affected by any drug treatment, suggesting that the observed effects on feeding were not due to a nonspecific reduction in motivated behavior. These findings revealed a synergistic interaction between the cannabinoid and melanocortin systems in feeding behavior. These results further suggested that CB1 receptors are located downstream from melanocortin receptors and CB1 receptor signaling is necessary to prevent the melanocortin system from altering food intake.
Hormonal signals produced by DAF-9/cytochrome P450 regulateC. elegansdauer diapause in response to environmental cues
Authors: Gerisch Birgit , Antebi Adam
Published: March 2004

In response to the environment, the nematode C. elegans must choose between arrest at a long-lived alternate third larval stage, the dauer diapause, or reproductive development. This decision may ultimately be mediated by daf-9, a cytochrome P450 related to steroidogenic hydroxylases and its cognate nuclear receptor daf-12, implying organism-wide coordination by lipophilic hormones. Accordingly, here we show that daf-9(+) works cell non-autonomously to bypass diapause, and promote gonadal outgrowth. Among daf-9-expressing cells, the hypodermis is most visibly regulated by environmental inputs, including dietary cholesterol. On in reproductive growth, off in dauer, hypodermal daf-9 expression is strictly daf-12 dependent, suggesting feedback regulation. Expressing daf-9 constitutively in hypodermis rescues dauer phenotypes of daf-9, as well as insulin/IGF receptor and TGFβ mutants, revealing that daf-9 is an important downstream point of control within the dauer circuits. This study illuminates how endocrine networks integrate environmental cues and transduce them into adaptive life history choices.
Divergent segmentation mechanism in the short germ insectTriboliumrevealed bygiantexpression and function
Authors: Bucher Gregor , Klingler Martin
Published: March 2004

Segmentation is well understood in Drosophila, where all segments are determined at the blastoderm stage. In the flour beetle Tribolium castaneum, as in most insects, the posterior segments are added at later stages from a posteriorly located growth zone, suggesting that formation of these segments may rely on a different mechanism. Nevertheless, the expression and function of many segmentation genes seem conserved between Tribolium and Drosophila. We have cloned the Tribolium ortholog of the abdominal gap gene giant. As in Drosophila, Tribolium giant is expressed in two primary domains, one each in the head and trunk. Although the position of the anterior domain is conserved, the posterior domain is located at least four segments anterior to that of Drosophila. Knockdown phenotypes generated with morpholino oligonucleotides, as well as embryonic and parental RNA interference, indicate that giant is required for segment formation and identity also in Tribolium. In giant-depleted embryos,the maxillary and labial segment primordia are normally formed but assume thoracic identity. The segmentation process is disrupted only in postgnathal metamers. Unlike Drosophila, segmentation defects are not restricted to a limited domain but extend to all thoracic and abdominal segments, many of which are specified long after giant expression has ceased. These data show that giant in Tribolium does not function as in Drosophila, and suggest that posterior gap genes underwent major regulatory and functional changes during the evolution from short to long germ embryogenesis.
Oxygen-regulated expression of the RNA-binding proteins RBM3 and CIRP by a HIF-1-independent mechanism
Authors: Wellmann Sven , Bührer Christoph , Moderegger Eva , Zelmer Andrea , Kirschner Renate , Koehne Petra , Fujita Jun , Seeger Karl
Published: March 2004

The transcriptional regulation of several dozen genes in response to low oxygen tension is mediated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric protein composed of two subunits, HIF-1α and HIF-1β. In the HIF-1α-deficient human leukemic cell line, Z-33, exposed to mild (8% O2) or severe (1% O2) hypoxia, we found significant upregulation of two related heterogenous nuclear ribonucleoproteins, RNA-binding motif protein 3 (RBM3) and cold inducible RNA-binding protein (CIRP), which are highly conserved cold stress proteins with RNA-binding properties. Hypoxia also induced upregulation of RBM3 and CIRP in the murine HIF-1β-deficient cell line, Hepa-1 c4. In various HIF-1 competent cells, RBM3 and CIRP were induced by moderate hypothermia (32°C) but hypothermia was ineffective in increasing HIF-1α or vascular endothelial growth factor (VEGF), a known HIF-1 target. In contrast, iron chelators induced VEGF but not RBM3 or CIRP. The RBM3 and CIRP mRNA increase after hypoxia was inhibited by actinomycin-D, and in vitro nuclear run-on assays demonstrated specific increases in RBM3 and CIRP mRNA after hypoxia, which suggests that regulation takes place at the level of gene transcription. Hypoxia-induced RBM3 or CIRP transcription was inhibited by the respiratory chain inhibitors NaN3 and cyanide in a dose-dependent fashion. However, cells depleted of mitochondria were still able to upregulate RBM3 and CIRP in response to hypoxia. Thus, RBM3 and CIRP are adaptatively expressed in response to hypoxia by a mechanism that involves neither HIF-1 nor mitochondria.
Study of the natural frequencies for two- and three-dimensional curved beams under rotational movement
Authors: Munteanu M Gh , Ray P , Gogu G
Published: March 2004

Dynamic analysis of highly elastically deformed bodies subjected to rotational movement is very important from a practical point of view: the centrifugal forces may considerably modify the body configuration. The classical large displacement theory is complicated and it leads to very time-consuming computer codes. In this work, a simple numerical method to study the dynamics of 3D beam systems is presented. The computing of the eigenfrequencies, taking into consideration the centrifugal stiffening effect even for very large displacements of elastic beams, is also developed. The elastic deformed configuration of one bent beam may be uniquely expressed only in rotations, or alternative parameters such as the Euler-Rodrigues quaternion, as functions of a curvilinear coordinate. The equations for the Euler-Bernoulli 3D beam model, written for the deformed beam, are solved. Consequently the equations are exact even for really large displacements. This approach leads to a non-incremental method and to a fast and accurate approach easy to program for computer applications. Passing from the absolute nodal coordinate formulation to the floating reference frame formulation becomes very easy, even natural.
New dual meshless flexible body methodology for multi-body dynamics: Simulation of generalized moving loads
Authors: Braccesi C , Landi L , Scaletta R
Published: March 2004

One of the main limits on the design phase of new mechanical components is the limited integration between the computer aided design (CAD) and the computer aided engineering (CAE) phases [1,2]. At present the virtual validation phase, carried out using various methods such as the finite element method (FEM) and multibody analysis (MBS), wastes a lot of time on model meshing, simplifications and database transfers. In recent years some new so-called meshless methodologies for CAx phase integration have been improved. In this paper the feasibility of a new meshless methodology based on spline geometry description is presented. Using this method it is possible to employ directly the B-spline CAD description to describe the physical behaviour of a general flexible body for all the CAE validation phases. Moreover, this method, taking advantage of its continuous formulation, is able to solve some important unsolved problems such as the generalized interactions between flexible bodies in multi-body analyses. In this paper the full method formulation is presented through curved beam implementation and examples.
Trends in Alkyl Substituent Effects on Nucleophilic Reactions of Carbonyl Compounds: Gas-Phase Reactions between Amines and the Methoxy Methyl Cation
Authors: Bache-Andreassen Lihn , Uggerud Einar
Published: March 2004

The reactions of various amines (RNH2: R = H, CH3, C2H5 and i-C3H7) with the methoxy methyl cation (CH2OCH3) have been investigated using a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, and the experimental results are complemented with ab initio calculations. The amines show clear trends in their reactivities with variable degree of: (1) nucleophilic substitution, (2) addition-elimination and (3) hydride abstraction. In all cases, addition–elimination dominates over nucleophilic substitution, and for R ≠ H the observed reactions occur at the collisional limit. The potential energy profiles for all three reaction types correlate with the basicities of the amines: i.e. the more basic the amine—the more favorable is the reaction. In other words, nucleophilicity follows basicity in the gas phase.
Mass Spectrometric Analysis of Chemical Warfare Agents and Their Degradation Products in Soil and Synthetic Samples
Authors: D'Agostino Paul A. , Hancock James R. , Chenier Claude L.
Published: March 2004

A packed capillary liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the identification of chemical warfare agents, their degradation products and related compounds in synthetic tabun samples and in soil samples collected from a former mustard storage site. A number of organophosphorus and organosulfur compounds that had not been previously characterized were identified, based on acquired high-resolution ESI-MS data. At lower sampling cone voltages, the ESI mass spectra were dominated by protonated, sodiated and protonated acetonitrile adducts and/or their dimers that could be used to confirm the molecular mass of each compound. Structural information was obtained by inducing product ion formation in the ESI interface at higher sampling cone voltages. Representative ESI-MS mass spectra for previously uncharacterized compounds were incorporated into a database as part of an on-going effort in chemical warfare agent detection and identification. The same samples were also analyzed by capillary column gas chromatography (GC)-MS in order to compare an established method with LC-ESI-MS for chemical warfare agent identification. Analysis times and full-scanning sensitivities were similar for both methods, with differences being associated with sample matrix, ease of ionization and compound volatility. GC-MS would be preferred for organic extracts and must be used for the determination of mustard and relatively non-polar organosulfur degradation products, including 1,4-thioxane and 1,4-dithiane, as these compounds do not ionize during ESI-MS. Diols, formed following hydrolysis of mustard and longer-chain sulfur vesicants, may be analyzed using both methods with LC-ESI-MS providing improved chromatographic peak shape. Aqueous samples and extracts would, typically, be analyzed by LC-ESI-MS, since these analyses may be conducted directly without the need for additional sample handling and/or derivatization associated with GC-MS determinations. Organophosphorus compounds, including chemical warfare agents, related compounds and lower volatility hydrolysis products may all be determined during a single LC-ESI-MS analysis. Derivatization of chemical warfare agent hydrolysis products and other compounds with hydroxyl substitution would be required prior to GC-MS analysis, giving LC-ESI-MS a definite advantage over GC-MS for the analysis of samples containing chemical warfare agents and/or their hydrolysis products.
Characterization and De Novo Sequencing of Atlantic Salmon Vitellogenin Protein by Electrospray Tandem and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry
Authors: Banoub Joseph , Cohen Alejandro , Mansour Atef , Thibault Pierre
Published: March 2004

Vitellogenin (VTG) is a protein produced by the liver of oviparous animals in response to circulating estrogens. In the plasma of males and immature females, VTG is undetectable. VTG has been used as a biomarker for exposure to endocrine disruptors in many species. In the present study, characterization of intact Atlantic salmon VTG was effected using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI ToF MS). Tryptic digest peptides were analyzed by MALDI ToF MS to obtain a peptide mass fingerprint. De novo sequencing of the tryptic peptides used low-energy collisionally-induced dissociation (CID) in an electrospray ionization quadrupole-ToF orthogonal hybrid mass spectrometer (ESI Q-ToF MS/MS). The interpretation of the product-ion spectra obtained from the ESI Q-ToF MS/MS was done by Lutefisk, a computer-based software algorithm. The molecular mass of the intact protein was found to be 187335 Da. A total of 14 tryptic peptides were sequenced and compared with the complete rainbow trout VTG and the partial Atlantic salmon VTG sequences found in the Swiss-Prot database. De novo sequencing by CID MS/MS of 11 Atlantic salmon tryptic digest peptides with selected precursor ions at m/z 788.24, 700.20, 794.75, 834.31, 889.28, 819.79, 865.27, 843.81, 572.20, 573.66 and 561.68 showed high homology with the known sequence of rainbow trout VTG. The last two precursor peptide ions, found at m/z 573.66 and m/z 561.68, also specifically matched the known portion of the Atlantic salmon VTG sequence. Finally, three tryptic precursor peptide ions found at m/z 795.18, 893.28 and 791.05, provided product-ion spectra, which were exclusive to the unsequenced portion of the Atlantic salmon VTG.
Unusual Covalent Bond-Breaking Reactions of β-cyclodextrin Inclusion Complexes of Nucleobases/Nucleosides and Related Guest Molecules
Authors: Vrkic Ana K. , O'Hair Richard A.J. , Lebrilla Carlito B.
Published: March 2004

Host–guest complexes between nucleobases or nucleosides and β-cyclodextrin can be observed by electrospray ionization mass spectrometry (ESI-MS) and their relative abundances appear to correlate with the condensed-phase binding order. Using Fourier transform ion cyclotron resonance mass spectrometry, the extent of the interactions between the host oligosaccharide and guest species have also been examined for permethylated β-cyclodextrin: adenine/deoxyadenosine and permethylated maltoheptaose: adenine/deoxyadenosine using gas-phase exchange reactions with the gaseous amines, n-propylamine and ethylenediamine. The ease of guest exchange in the gas-phase follows the order: deoxyadenosine > adenine ≪ deoxycytidine > cytosine, which is in contrast to their relative binding order in solution. Collision-induced dissociation (CID) has been used to probe the fragmentation behavior of oligosaccharide: nucleobase/nucleoside complexes. Under these conditions the inclusion complexes either (a) dissociate, (b) result in cleavage of the host oligosaccharide or (c) result in cleavage of the guest molecule. This study has shown that the preferred dissociation pathway of these complexes depends on the structures of both the cyclodextrin and guest molecule.
Variable-Temperature Ion Mobility Time-of-Flight Mass Spectrometry Studies of Electronic Isomers of Kr2+ and CH3OH+• Radical Cations
Authors: Verbeck G.F. , Gillig K.J. , Russell D.H.
Published: March 2004

Preliminary results from a liquid nitrogen-cooled ion mobility (IM) orthogonal-time-of-flight (o-ToF) mass spectrometer applied to the separation of electronic isomers of Kr2+ and methanol radical cations (conventional and distonic) are presented. Ab initio calculations were used to estimate the energies and energy barriers to interconversion between conventional (CH3OH•+) and distonic (CH2•OH2+) radical cations. In addition, computations and experiments are used to compare ion-neutral collision cross-sections for CH3OH•+ and CH2•OH2+ radical cations and suggest that the mobility separation is achieved by ion-neutral interactions between ions and neutral buffer gas.
Ion/Molecule Reactions of Isomeric Bromobutene Radical Cations with Ammonia
Authors: Grützmacher Hans-Friedrich , Büchner Michael
Published: March 2004

The ion/molecule reaction of the radical cations of three isomeric bromobutenes (2-bromobut-2-ene 1, 1-bromobut-2-ene 2, 4-bromobut-1-ene 3) with ammonia were studied by Fourier transform ion cyclotron resonance spectrometry to reveal the effect of a different position of the bromo substituent relative to the C–C double bond. Further, the reaction pathways of the ion/molecule reactions were analyzed by theoretical calculations at the level B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d). All three bromobutene radical cations 1•+ to 3•+ react efficiently with NH3. The reactions of 1•+ carrying the halogen substituent at the double bond follow the pattern observed earlier for other ionized vinylic halogenoalkenes. The major reaction corresponds to proton transfer to NH3 as to be expected from the high acidity of but-2-ene radical cations exposing six acidic H atoms at allylic positions. The other, still important, reaction of 1•+ is substitution of the Br substituent by NH3. Although the radical cations 2•+ and 3•+ are expected to be as acidic as 1•+, proton transfer is the minor reaction pathway of these radical cations. Instead, 2•+ displays bomo substitution as the major reaction. It is suggested that the mechanism of this reaction is analogous to SN2′ of nucleophilic allylic substitution. Substitution of Br is not efficient for the reactions of 3•+—the two major reactions correspond to C–C bond cleavage of the two possible β-distonic ammonium ions which are generated by the addition of NH3 to the ionized double bond of 3. This observation, as well as the results obtained or 1•+ and 2•+, emphasize the role of the fast and very exothermic addition of a nucleophile to the ionized double bond for the ion/molecule reactions of alkene radical cations. Clearly the energetically-excited distonic ion arising from the addition fragments unimolecularly by energetically accessible pathways. In the case of a halogene subsituent (except F) at the vinylic or allylic position, this is loss of the subsituent. In the case of remote halogeno substituents, this is C–C bond cleavage adjacent to the radical site of the distonic ion.
Clinical Experience with Moxifloxacin in Patients with Respiratory Tract Infections
Authors: Faich Gerald A , Morganroth Joel , Whitehouse Alan B , Brar Jugroop S , Arcuri Peter , Kowalsky Steven F , Haverstock Daniel C , Celesk Roger A , Church Deborah A
Published: March 2004

BACKGROUND

Moxifloxacin is an advanced-generation fluoroquinolone used primarily for the treatment of respiratory tract infections.

OBJECTIVE

To further investigate moxifloxacin's general and cardiac safety and evaluate its efficacy in the community practice setting in a large surveillance study.

METHODS

A total of 18 409 outpatients with suspected bacterial episodes of acute sinusitis, acute exacerbation of chronic bronchitis, or community-acquired pneumonia of mild to moderate severity were enrolled at 3377 community practice sites. Patients with sinusitis or pneumonia received once-daily oral moxifloxacin 400 mg for 10 days; those with bronchitis received 5 days' treatment. At follow-up, within 48 hours after the end of treatment, adverse event information was collected. An external safety committee assessed possible cardiac-related events. Efficacy was also evaluated at follow-up via the degree of resolution of clinical signs and symptoms.

RESULTS

Of 18 374 safety-valid patients, 17.7% experienced adverse events and 14.3% experienced drug-related adverse events. The most common drug-related adverse events were nausea (5.3%), diarrhea (2.2%), and dizziness (2.0%). There was no clinical evidence of increased risk of cardiac arrhythmias with moxifloxacin treatment. Of 17 137 patients included in the efficacy analysis, 92.9% overall experienced clinical cure or improvement (92.8% with sinusitis, 92.9% with bronchitis, 94.1% with pneumonia).

CONCLUSIONS

Once-daily oral moxifloxacin 400 mg was shown to be safe and effective in this trial for the treatment of respiratory tract infections of suspected bacterial origin in the clinical practice setting.
High- Versus Low-Dose ACE Inhibitor Therapy in Chronic Heart Failure
Authors: Roffman David S
Published: March 2004

OBJECTIVE

To discuss the controversy associated with the optimal dosing of angiotensin-converting enzyme (ACE) inhibitors in the management of patients with systolic heart failure; specifically, to review data related to the use of high-dose ACE inhibitors related to both neurohormonal and clinical outcomes associated with doses similar to, lower than, and higher than those used in the large, randomized clinical trials.

DATA SOURCES

Primary, review, and meta-analysis articles were identified by MEDLINE search (1987–September 2002) and through secondary sources.

STUDY SELECTION AND DATA EXTRACTION

All of the articles identified from the data sources were evaluated, and all information deemed relevant was included in this discussion. All available comparative dose trials, both prospective and retrospective, were evaluated for clinical and neurohormonal outcomes.

DATA SYNTHESIS

The majority of data comparing the effect of high- with low-dose ACE inhibitors on neurohormonal outcomes demonstrate dose-related reduction in various neurohormonal measurements including plasma ACE, aldosterone, atrial natriuretic peptide, B-type natriuretic peptide, and interleukin-6 levels. Clinical endpoints including New York Heart Association class and heart failure—related hospitalizations were reduced by higher doses, but a dose-related survival benefit has not been demonstrated. Differences in duration of therapy and study design may account for variability in neurohormonal and morbidity results among various studies.

CONCLUSIONS

Despite documented underutilization in clinical practice of doses of ACE inhibitors demonstrated in large controlled trials to improve morbidity and mortality, clinicians should attempt to reach these target doses if possible in patients with heart failure. Higher doses may improve surrogate markers for heart failure without impacting survival.
Mikroelektronischer Haushaltsgaszähler mit neuer Technologie (Microelectronic Domestic Gas Meter with New Technology)
Authors: Matter Daniel , Kramer Beat , Kleiner Thomas , Sabbattini Bruno , Suter Tobias
Published: March 2004

In der hier vorgestellten Neuentwicklung wird aktuellste „Sensor-on-chip“-Technologie eingesetzt, um das mehr als 150 Jahre alte Prinzip der Haushalts- und Gewerbegaszähler in eine neue Generation zu führen. Dieser Technologie-Quantensprung findet in einem Weltmarkt mit Stückzahlen von 20 Millionen Gaszählern pro Jahr statt, was einem jährlichen Umsatz von ca. 1 Milliarde € entspricht und daher eine hohe wirtschaftliche Bedeutung hat. Das neue Gerät ist kleiner, genauer und bietet weitere Vorteile bei gleichen Produktionskosten wie jene für die alte Technik.
Environmental Study in Subway Metro Stations in Cairo, Egypt
Authors: Awad Abdel Hameed A.
Published: March 2004

Environmental Study in Subway Metro Stations in Cairo, Egypt: Abdel Hameed A. Awad, Air Pollution Department, National Research Centre—Airborne viable and non‐viable measurements were carried out in two different metro stations, one located in a tunnel and the other on the surface. The concentrations of airborne total viable bacteria (incubated at 37°C and 22°C), staphylococci, suspended dust and oxidants (ozone) were higher in the air of the tunnel station than those recorded at the surface station. In contrast, spore forming bacteria, Candida spp, fungi and actinomycetes were found at slightly higher levels in the surface station than in the tunnel station. A statistically significant difference (p<0.01) was found between the levels of suspended dust at both stations. Cladosporium, Penicillium and Aspergillus species were the dominant fungi isolates. Fusarium, Aspergillus and Penicillium are the most common fungi that produce toxins. Under certain circumstances (host susceptibility, infective dose and aerodynamic diameter) some of the airborne microorganisms e.g. actinomycetes and Aspergillus species and staphylococci may cause health problems in exposed persons based on toxic or allergic reactions.
Occupational Exposure to Indoor Allergens in Finnish Trained Home‐Helpers: a Pilot Study
Authors: Pennanen Sirpa , Harju Anu , Merikoski Raisa , Pasanen Anna‐Liisa , Liesivuori Jyrki
Published: March 2004

Occupational Exposure to Indoor Allergens in Finnish Trained Home‐Helpers: a Pilot Study: Sirpa Pennanen, et al. Kuopio Regional Institute of Occupational Health—The presence of allergies, respiratory symptoms and skin‐prick reactions was evaluated in trained home‐helpers (THH), and indoor allergen levels were measured at their work sites. A questionnaire was answered by 118 THHs and forty THHs consented to skin‐prick tests. The indoor allergen levels in the settled house dust from the clients’ homes of 17 prick tested THHs were determined by two‐site monoclonal antibody ELISA methods. Forty‐ eight percent of the THHs had one or more symptoms at least weekly. The presence of respiratory symptoms and atopy was not particularly high in THHs. Prick tests revealed that 11 THHs (28%) had positive reactions to one or more of the allergens tested. A significant correlation was observed between the frequency of reported symptoms and positive prick reactions. Fel d 1 was found in 98% and Can f 1 in 96% of the dust samples, but Der p 1 in only 21% of the samples, though the levels remained rather low. The sensitization threshold suggested for cat allergen (1 μ g/g) was exceeded in 26%, and that for dog allergen (2 μg/g) in 32% of the sites studied. These results showed that THHs are occupationally exposed to allergen levels sufficient to result in sensitization.
Urinary Excretion of TTCA after Intake of brassica Vegetables
Authors: Kikuchi Yuriko , Uemura Takamoto , Yamauchi Tsuneyuki , Takebayashi Torn , Nishiwaki Yuji , Yamada Kenichi , Sakurai Haruhiko , Omae Kazuyuki
Published: March 2004

Urinary Excretion of TTCA after Intake of brassica Vegetables: Yuriko Kikuchi, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—Aim: Recent studies have made it clear that brassica vegetables contain 2‐thiothiazolidine‐4‐carboxylic acid (TTCA), which is the most widely used biological monitoring index of exposure to carbon disulfide (CS2). This study aimed to assess the time‐course of TTCA excretion in urine (TTCA‐U) after eating brassica vegetables. Methods: After a 1‐d break from eating brassica vegetables, ten volunteers (6 males and 4 females) ingested 100 grams of chopped raw cabbage containing 4.3 mg/kg of TTCA, and the TTCA concentration in urine samples was determined over 24 h. TTCA concentrations in brassica vegetables purchased from a local supermarket were also measured. Results: TTCA‐U reached peak concentrations 3‐9 h after cabbage intake, gradually decreased, and was below the detection limit (<0.1 mg/I) in 8 of 10 volunteers in the last urine samples. The total amount of TTCA excreted in 24 h ranged from 0.19 to 0.42 mg, and half of the total TTCA was excreted within 6.5 h on average (range: 4.5‐10.1). The excretion profiles of young and middle‐aged volunteers seemed to differ, but not those of young males and young females. TTCA was detected in both raw and boiled cabbage, Japanese radish, turnip, and broccoli, but was not detected in Chinese cabbage or chingentsuai. Conclusion: TTCA‐U may be overestimated as an index of CS2 exposure when brassica vegetables are ingested within approximately 24 h before collection of the urine sample.
Cadmium Concentration in Current Japanese Foods and Beverages
Authors: Kikuchi Yuriko , Nomiyama Tetsuo , Kumagai Nami , Uemura Takamoto , Omae Kazuyuki
Published: March 2004

Cadmium Concentration in Current Japanese Foods and Beverages: Yuriko Kikuchi, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—

Aims

The present study was to determine the cadmium (Cd) concentrations in ordinarily consumed foods and beverages in Japan.

Methods

Cd concentrations in 519 foods and beverages purchased from a local market were measured with the flame or flameless atomic absorption spectrophotometer (AAS).

Results

The Cd concentration in each food group was as follows: cereals 0.004‐0.380 μg/g, potatoes <0.01‐ 0.08 μg/g, sugars and sweeteners <0.01 μg/g, pulses <0.010‐0.220 μg/g, nuts and seeds <0.01‐0.18 μg/g, vegetables (grown in soil) <0.001‐0.128 μg/g, vegetable (grown by means of hydroponics) <0.001‐ 0.002 μg/g, fruits <0.001‐0.033 μg/g, mushrooms <0.01‐0.19 μg/g, algae 0.040‐2.380 μg/g, fish <0.01‐ 0.02 μg/g, shellfish <0.010‐5.050 μg/g, meats <0.001‐ 0.100 μg/g, eggs <0.001 μg/g, milk <0.010 μg/g, fats and oils <0.001‐0.001 μg/g, confectioneries <0.020‐ 0.100 μg/g, beverages <0.01‐0.13/rg/g, seasoning and spices <0.01‐0.06 μg/g, and various supplement tablets <0.001‐0.036 μg/g.

Conclusion

A database of Cd content in foods was compiled. Cd in cereals varied from 0.004 to 0.380 μg/g. Algae, shellfish and pulses contained much higher concentrations of Cd. Vegetables grown by hydroponic cultivation contained only a very low or undetectable amount of Cd. Estimation of dietary Cd intake from the database could provide a reasonable method for estimating the relative contributions of different food groups to dietary Cd intake.
Influence of Work Type on Sickness Absence among Personnel in a Teaching Hospital
Authors: Lim Apiradee , Chongsuvivatwong Virasakdi , Geater Alan , Chayaphum Nongklarn , Thammasuwan Ussanee
Published: March 2004

Influence of Work Type on Sickness Absence among Personnel in a Teaching Hospital: Apiradee Lim, et al. Epidemiology Unit, Faculty of Medicine, Prince of Songkla University—Sickness absence among hospital personnel with different work types was compared. Sickness absence records were collected for all personnel in the Faculty of Medicine, Prince of Songkla University, a medical school in southern Thailand with a 750‐bed teaching hospital, from October 1995 to September 1998, and analysed using descriptive statistics and negative binomial regression. Doctors and nurses recorded lower rates of short‐term sickness absence (< 3 d) than other workers. Doctors also recorded the lowest rate of long‐term absence (> 3 d), whereas other medical personnel and manual workers had higher rates of long‐term sickness absence than other workers. These differences were only slightly influenced by sex, age and marital status. Rates of short‐ term sickness absence were higher in males, older and married personnel. A higher grade of employment was associated with lower sickness absence, both short‐ and long‐term, and accounted for much of the actual differences among work types. Nevertheless, significant differences across work type remained after adjustment for socio‐demographic and other work‐related variables. The findings of this study would provide new baseline information regarding sickness absence patterns among hospital staff in this particular setting, but there is still a need to distinguish among the true reasons for reported sickness absence, particularly short‐term absence, in order to set up an appropriate health promotion programme among the staff of this hospital.
Carcinogenicity and Chronic Toxicity in Rats and Mice Exposed to Chloroform by Inhalation
Authors: Yamamoto Seigo , Kasai Tatsuya , Matsumoto Michiharu , Nishizawa Tomoshi , Arito Heihachiro , Nagano Kasuke , Matsushima Taijiro
Published: March 2004

Carcinogenicity and Chronic Toxicity in Rats and Mice Exposed to Chloroform by Inhalation: Seigo Yamamoto, et al. Japan Bioassay Research Center—A bioassay study of carcinogenicity and chronic toxicity of chloroform was undertaken by inhalation exposures of groups of 50 F344 rats and 50 BDF1 mice of both sexes to chloroform for 6 h/d x 5 d/ wk X 104 wk. The exposure concentration was 0 (control), 10, 30 or 90 ppm for rats and 0, 5, 30 or 90 ppm for mice. Combined incidences of renal cell adenomas and carcinomas, and of hepatocellular adenomas and carcinomas increased in the exposed male and female mice, respectively. Incidences of atypical tubule hyperplasia, cytoplasmic basophilia and nuclear enlargement in the kidneys and fatty change in the liver increased in the exposed male mice. Increased incidence of altered cell foci in the exposed female mice was causally related to the hepatocellular adenomas and carcinomas. No significantly increased incidence of the kidney or liver tumors was observed in the exposed rats of either sex. Increased incidences of nuclear enlargement and dilatation of tubular lumen were found in the kidneys of exposed rats. No‐ observed‐adverse‐effect‐levels (NOAELs) for the biologically significant endpoint were determined from the dose‐response relationships of the present datasets. The NOAEL for the histopathological endpoint of the kidneys resulted in 5 ppm for mice and 10 ppm for rats. An occupational exposure limit for chloroform was discussed in light of the NOAELs.
Acceptability and Long‐Term Compliance with Drug Treatment for Hypercholesterolemia in Japanese Male Workers
Authors: Tatemichi Masayuki , Hamaguchi Tsutahiro , Hashira Munetaka , Hayashi Takeshi , Ito Masato , Nakatani Atsushi , Hiro Hisanori , Mori Koji , Okubo Yasushi , Ezaki Takafumi , Sugimori Hiroki , Yoshida Katsumi
Published: March 2004

Acceptability and Long‐Term Compliance with Drug Treatment for Hypercholesterolemia in Japanese Male Workers: II. Long‐Term Compliance with Drug Treatment: Masayuki Tatemichi, et al. Department of Environmental and Occupational Health, Toho University School of Medicine—We undertook a prospective study to assess the long‐term compliance of Japanese male workers with drug treatment for hypercholesterolemia. In workers who accepted treatment with simvastatin, an HMG‐CoA reductase inhibitor, compliance was monitored every 6 months with an interview. Factors affecting compliance were identified by using the background characteristics of subjects and a self‐administered questionnaire on their type of job, job style, private lifestyle and psychological status at work. Mean (SD) follow‐up periods were 21.5 (10.6) months for 640 workers, and 240 noncompliant (< 75 % of prescription) subjects were found. Of these 240, 23 (9.6%) were restored to be finally compliant at the last follow‐up (re‐compliant). We assessed the time‐course rate of compliant subjects and factors affecting drug compliance using Cox proportional hazard model by setting occurrence of a noncompliant attitude to an endpoint. The cumulative compliance rate at 36 months was 0.508 when excluding 23 re‐compliant subjects and 0.529 when considering them as compliant. Multivariate analysis showed that age and present medical illness with hypertension (HT) in background characteristics of subjects and the habit of having breakfast daily in factors related to private‐lifestylewere significantly associated with compliance. Baseline lipid profiles and work related issues were not associated with compliance. The occurrence rate of side effects did was similar in compliant and noncompliant workers. In this study, even though considering the re‐compliant subjects, the rate of compliant subjects over a 3‐yr period was considerably low (around 50%). The factors related to compliance were age, present illness with HT and the habit of having breakfast daily.
Urinary Tract Infection among Clean‐Room Workers
Authors: Wang Jian‐Nan , Su Shih‐Bin , Guo How‐Ran
Published: March 2004

Urinary Tract Infection among Clean‐Room Workers: Jian Nan Wang1, et al.1 Department of Family Medicine, Chie‐Mei Foundation Hospital—Many high‐tech industries do some manufacturing processes in clean‐rooms to ensure high quality and yield. To prevent contamination, workers need to put on special clothing and go through certain cleaning procedures before entry. Therefore, some workers may limit their water intake and try not to go the bathroom, which are both risk factors of urinary tract infection (UTI). To assess the prevalence and risk factors of UTI among the workers, we conducted a study in an industrial park. We recruited workers who came to the clinic in the park for an annual health examination between September 1 and December 31, 2000. From each participant we collected a urine sample and obtained related information through a questionnaire. All the 1,054 qualified workers, including 416 men and 638 women, participated, and 693 (65.7%) were clean‐room workers. Most clean‐room workers were women (71.3%), and they tended to be younger and had lower frequencies of drinking water and going to the bathroom during the shift. A higher prevalence of UTI (6.2% vs. 2.5%, p = 0.008) was observed among clean‐room workers. After adjusting for age, frequency of dinking water, and working in clean‐rooms, female gender was a significant risk factor (odds ratio [OR] = 18.3, 95% confidence interval [Cl]: 4.1 to 82.1) and going to the bathroom three times or more during a shift was a protective factor (OR = 0.3, 95% Cl: 0.1 to 1.0). In conclusion, UTI is prevalent among clean‐room workers, and frequent voiding is recommended for prevention of the disease.