bluuebunny/crossref_metadata_2025 huggingface dataset:
Emission sources and ocean uptake of acetonitrile (CH3CN) in the atmosphere
Authors: de Gouw J. A. , Warneke C. , Parrish D. D. , Holloway J. S. , Trainer M. , Fehsenfeld F. C.
Published: June 2003

Airborne measurements of acetonitrile (CH3CN) were made off the U.S. west coast, over California, and during two transfer flights over the U.S. in April and May of 2002. Acetonitrile was strongly enhanced in the plumes from two forest fires, confirming the usefulness of the measurement as an indicator for biomass burning emissions. The emission ratios relative to CO of acetonitrile in the two plumes were slightly higher than previously reported values for fires burning in other fuel types. No significant acetonitrile release was observed in the Los Angeles basin or from other point sources (ships and a power plant). Acetonitrile concentrations were significantly reduced in the marine boundary layer indicating the presence of an ocean uptake sink. Increased loss of acetonitrile was observed close to the coast, suggesting that acetonitrile was efficiently lost by dissolving in the upwelling ocean water, or by biological processes in the surface water.
Photolysis frequency of NO2: Measurement and modeling during the International Photolysis Frequency Measurement and Modeling Intercomparison (IPMMI)
Authors: Shetter R. E. , Junkermann W. , Swartz W. H. , Frost G. J. , Crawford J. H. , Lefer B. L. , Barrick J. D. , Hall S. R. , Hofzumahaus A. , Bais A. , Calvert J. G. , Cantrell C. A. , Madronich S. , Müller M. , Kraus A. , Monks P. S. , Edwards G. D. , McKenzie R. , Johnston P. , Schmitt R. , Griffioen E. , Krol M. , Kylling A. , Dickerson R. R. , Lloyd S. A. , Martin T. , Gardiner B. , Mayer B. , Pfister G. , Röth E. P. , Koepke P. , Ruggaber A. , Schwander H. , van Weele M.
Published: June 2003

The photolysis frequency of NO2, j(NO2), was determined by various instrumental techniques and calculated using a number of radiative transfer models for 4 days in June 1998 at the International Photolysis Frequency Measurement and Modeling Intercomparison (IPMMI) in Boulder, Colorado. Experimental techniques included filter radiometry, spectroradiometry, and chemical actinometry. Eight research groups participated using 14 different instruments to determine j(NO2). The blind intercomparison experimental results were submitted to the independent experimental referee and have been compared. Also submitted to the modeling referee were the results of NO2 photolysis frequency calculations for the same time period made by 13 groups who used 15 different radiative transfer models. These model results have been compared with each other and also with the experimental results. The model calculation of clear‐sky j(NO2) values can yield accurate results, but the accuracy depends heavily on the accuracy of the molecular parameters used in these calculations. The instrumental measurements of j(NO2) agree to within the uncertainty of the individual instruments and indicate the stated uncertainties in the instruments or the uncertainties of the molecular parameters may be overestimated. This agreement improves somewhat with the use of more recent NO2 cross‐section data reported in the literature.
Organic nitrogen in rain and aerosol in the eastern Mediterranean atmosphere: An association with atmospheric dust
Authors: Mace Kimberly A. , Kubilay Nilgün , Duce Robert A.
Published: June 2003

From March through early May of 2000, rain and bulk aerosol samples were collected at a coastal site on the eastern Mediterranean Sea at Erdemli, Turkey, and analyzed for nitrogen (N) species, including nitrate (NO3−), nitrite (NO2−), ammonium (NH4+), water‐soluble organic N, urea, and dissolved free amino acids. Other ions were also analyzed, including Ca2+, Mg2+, K+, Na+, Cl−, and SO42−. Water‐soluble organic N was found to contribute ∼17% and ∼26% of the total water‐soluble N in rain and aerosols, respectively. Organic N concentrations within rain and aerosols exhibited statistically significant linear relationships to Ca2+ ion (Rsqr ∼ 0.75, P < 0.05), suggesting a relationship to calcite (CaCO3) in atmospheric dust. Kinematic trajectory analyses indicated the origin of winds from arid regions, mainly in northern Africa, in 70% of the aerosols sampled. Earth Probe/Total Ozone Mapping Spectrometer aerosol index data also confirmed the influence of atmospheric dust in the region on days when Ca2+ concentrations were elevated, and trajectory analyses suggested northern Africa as a source region. The combined ion, trajectory, and aerosol index data suggest that organic N is associated with atmospheric dust in this region. Urea N and amino N represented a small percentage of the organic N fraction. In rain and aerosols, urea represented ∼11% and <1%, respectively, of the total organic N. While amino N contributed minimally to organic N totals (∼1% of total organic N in aerosols), the individual amino acids contributing ∼75% of amino N were indicative of biological organisms. Further research is needed to decipher the influence from biology and gas phase adsorption of anthropogenically derived water‐soluble organics on organic N totals.
Inversion of Odin limb sounding submillimeter observations by a neural network technique
Authors: Jiménez Carlos , Eriksson Patrick , Murtagh Donal
Published: June 2003

The limb sounder radiometer on board the satellite Odin is the first instrument measuring emission from space in the submillimeter region to map atmospheric species. Nonlinear inversions of Odin spectra by iterative approaches are computationally very intensive, so a faster neural network technique has been developed. The technique is tested here by inverting simulated observations in the 544.2‐545.0 GHz band, retrieving O3by the neural networks and an optimal estimation approach based on the Marquardt‐Levenberg algorithm. Special consideration is given here to the implementation of a spectral reduction technique and the treatment of the main random uncertainties. The reduction technique is based on deriving spectral eigenvectors from the weighting functions of the observations and successfully reduced the dimensionality of the spectral space by two orders of magnitude. The random uncertainties are treated by incorporating their possible realizations into the training sets, and inversion of simulated spectra with thermal noise, temperature, and pointing uncertainties gave similar retrieval errors for the neural networks and optimal estimation, with the neural networks being much faster. However, a problem remains because optimal estimation can easily incorporate last‐minute a priori information that reduces the random uncertainty and subsequently the retrieval error, but it is not so easy for the neural networks to incorporate the same information.
A change of microwave radiation from the ocean surface induced by air‐sea temperature difference
Authors: Shibata Akira
Published: June 2003

We investigate microwave radiation from the ocean surface to observe changes in microwave radiation for various air‐sea temperature differences by using data of the Special Sensor Microwave/Imager 19 GHz and the TRMM Microwave Imager 19 and 10 GHz. To this end, we developed a method of removing the atmospheric effect. Under strong winds exceeding 7m/s, atmospheric‐effect‐removed temperatures of both vertical and horizontal polarizations increase, and the ratio of the V/H increase in stable condition is less than that in neutral or unstable conditions. Furthermore, in neutral or unstable conditions, the ratio of the V/H increasing at 10GHz is larger than that at 19GHz.
A tropical mechanism for Northern Hemisphere deglaciation
Authors: Rodgers K. B. , Lohmann G. , Lorenz S. , Schneider R. , Henderson G. M.
Published: June 2003

We investigate the role of the tropics in the melting and reforming of the Laurentide ice sheet on glacial timescales using an atmospheric general circulation model. It is found that warming of tropical sea surface temperatures (SSTs) from glacial boundary conditions, as observed at the end of glacial periods, causes a large increase in summer temperatures centered over the ice sheet‐forming regions of Canada. This high‐latitude response to tropical change is due to relatively small changes in the circulation of the extratropical atmosphere, which lead to changes in the vertical profiles of temperature and moisture in the extratropical atmosphere. The maximum perturbation in the summer radiative balance over the Laurentide ice sheet (>25 W/m2) due to the changes in the local atmospheric water vapor inventory is much larger than that induced by glacial to interglacial changes in atmospheric CO2. These changes via an atmospheric bridge between the tropics and extratropics represent a mechanism for deglaciations which is consistent with timing constraints. In contrast, a cold perturbation to tropical SST for interglacial boundary conditions results in only very small changes in the delivery of water vapor to the Laurentide region, and therefore almost no cooling over the Canadian region. This implies that tropical SSTs could play a more important role in melting ice sheets in the Northern Hemisphere than in reforming them, possibly providing a mechanism which could help to explain the rapidity of deglaciation relative to glacial inception.
Climatology of the upper mesosphere temperature above South Pole (90°S): Mesospheric cooling during 2002
Authors: Hernandez G.
Published: June 2003

Polar mesospheric temperature measurements obtained above South Pole from 1991 through 2002 are shown, and their long‐term behavior ‐climatology‐ has been deduced. The variation of this temperature during the polar night shows an annual amplitude of 14 K about the mean yearly value. A strong and highly significant correlation is found between the mean yearly temperature and the solar activity ‐expressed as the F10.7 flux‐, giving a 13 K change per 100 unit F10.7 change. The mean measured 2002 polar night temperatures are about 35 K cooler than the mean for the previous 11 years and well outside their excursions about this mean. This observed mesospheric cooling is in keeping with the disturbed lower atmosphere reported for this period. Other effects from the latter include both a smaller austral ozone depletion hole than has been recorded in previous years and higher than average minimum temperatures in the south polar region. The observed mesospheric cooling resembles the cooling observed at Northern midlatitudes during stratospheric warmings.
Tri(propylene glycol) glycerolate diacrylate cross‐linked polystyrene: a new resin support for solid‐phase peptide synthesis
Authors: Sasikumar P.G. , Kumar K.S. , Rajasekharan Pillai V.N.
Published: May 2003

Abstract: A highly flexible, mechanically and chemically stable copolymer, tri(propylene glycol) glycerolate diacrylate cross‐linked polystyrene (PS‐TRPGGDA), was synthesized by the suspension polymerization and employed as a solid support for peptide synthesis. The beaded polymer support containing secondary hydroxyl functional groups in the cross‐linker was used as the growth site for peptide synthesis. The procedure is unique and cost‐effective in that it avoids the initial functionalization steps required for most of the styrene‐based polymer supports. The resin was characterized by 13C‐CP‐MAS NMR spectroscopy and the morphologic features of the resin were investigated using scanning electron microscopy. Swelling studies conducted on the new support revealed that the PS‐TRPGGDA resin undergoes more effective swelling and solvation than PS‐DVB resin in all solvents used in peptide synthesis. The efficiency of the new support was demonstrated by synthesizing a ‘difficult’ sequence Ala‐Arg‐(Ala)6‐Lys and comparing it with commercially available Merrifield and Sheppard resins. The synthetic efficiency was further demonstrated by the synthesis of a 24‐residue NR 2A peptide substrate of calcium/calmodulin‐binding peptide. The high yield and purity of the peptide synthesized on the novel support indicates the positive role of the flexible and hydrophilic cross‐linking agent in the solid support.
Fatty acids in breast milk of allergic and non‐allergic mothers: The PIAMA birth cohort study
Authors: Wijga Alet , Houwelingen Adriana C. v. , Smit Henriëtte A. , Kerkhof Marjan , Vos Ada P. H. , Neijens Herman J. , Brunekreef Bert
Published: June 2003

Fatty acid composition was studied in breast milk of allergic and non‐allergic mothers, focusing in particular on concentrations of the n‐6 and n‐3 long‐chain polyunsaturates (LCP) in relation to maternal allergy. Milk samples were obtained from 168 mothers with asthma or inhalant allergies and 107 mothers without asthma and inhalant allergies, between 2 and 35 weeks after delivery. Mean values of fatty acid concentration (weight% of total fatty acids) were estimated for individual fatty acids, for groups of fatty acids and for the metabolic index (the ratio between the sum of n‐6 polyunsaturates and linoleic acid). For the most relevant fatty acids, the association with maternal allergy was subsequently analyzed in more detail using multiple regression analysis. The metabolic index in breast milk was significantly lower in the allergic than in the non‐allergic mothers, but no significant differences were observed in the concentrations of any of the n‐6 fatty acids. Also concentrations of the n‐3 fatty acids and nearly all other fatty acids were similar in allergic and non‐allergic mothers' breast milk. No differences in fatty acid concentrations were observed between mothers with asthma and mothers with single or with multiple inhalant allergies. Our data suggest that differences in fatty acid composition between breast milk of allergic and non‐allergic mothers are small and are unlikely to be responsible for the differential effects of breastfeeding by allergic and non‐allergic mothers that have been observed in some studies.
Treatment‐latency and previous episodes: relationships to pretreatment morbidity and response to maintenance treatment in bipolar I and II disorders
Authors: Baldessarini Ross J , Tondo Leonardo , Hennen John
Published: May 2003

Objective: To clarify relationships of treatment delay and pretreatment episode count with pretreatment morbidity and responses to maintenance treatments in bipolar disorders.

Methods: In 450 DSM‐IV bipolar I (n = 293) or II (n = 157) patients (280 women, 170 men), we evaluated correlations of latency from illness‐onset to starting maintenance treatment and pretreatment episode counts with pretreatment morbidity and treatment response. We considered morbidity measures before and during treatment, and their differences.

Results: Latency averaged 7.8 years, with 9.0 episodes per patient, before various maintenance treatments started. Morbidity (percentage of time‐ill, episodes per year, first wellness‐interval, or proportion of subjects hospitalized or having no recurrences) during maintenance treatment averaging 4.2 years was unrelated to treatment latency or pretreatment episode count. However, pretreatment morbidity was greater with shorter latency, resulting in larger relative reduction of morbidity after earlier treatment.

Conclusions: Greater treatment latency and pretreatment episode count were not followed by greater morbidity during treatment, although longer delay yielded smaller during‐versus‐before treatment reduction in morbidity. Predictions that longer treatment delay or more pretreatment episodes lead to poorer responses to various maintenance treatments in bipolar I or II disorder were not supported.
Career counsellors and occupational contact dermatitis
Authors: Saunders Helen , Keegel Tessa , Nixon Rosemary , Frowen Kath
Published: May 2003

Career counsellors are in a unique position to provide timely preventive advice to young people at risk of developing occupational contact dermatitis. Career counsellors need to be aware of risk factors for this condition, including atopic eczema, and of high‐risk occupations, such as hairdressing. A cross‐sectional survey of 82 career counsellors was conducted at an Australian career counsellors' conference. 24 (29%, 95% confidence interval (95% CI) 19–40%) correctly identified eczema as a risk factor. 25 (30%, 95% CI 21–41%) indicated consideration of past skin problems during career counselling. 30 (36%, 95% CI 25–47%) correctly reported at least 1 high‐risk occupation, with hairdressing being most frequently identified. Only 3 of the 82 (4%, 95% CI 0–7%) correctly answered all 3 questions.
Use of in vitro release of interferon‐γ in the diagnosis of contact allergy to potassium dichromate – a controlled study
Authors: Trattner A. , Akerman L. , Lapidoth M. , Klein T. , Weiss H. , Ben Chaim B. , David M.
Published: May 2003

The use of in vitro release of interferon‐γ (IFN‐γ) in the diagnosis of contact allergy to potassium dichromate was studied in 20 patients who had positive patch tests to chromate and in 30 control subjects (10 patients with contact dermatitis, allergic to other allergens, 10 patients with other dermatologic diseases and 10 healthy subjects). The release of IFN‐γ in the supernatants of the peripheral blood lymphocytes was significantly higher in the patients with proven allergy to chromate (P = 0·001). Further studies are needed to determine if IFN‐γ release may serve as an additional diagnostic tool in contact dermatitis.
Papular dermatitis and a persistent patch test reaction to gold sodium thiosulfate
Authors: Sperber Brian R. , Allee Julie , Elenitsas Rosalie , James William D.
Published: May 2003

The role of gold in allergic contact dermatitis is poorly understood and is a subject of increasing interest. Recent studies demonstrate that gold‐positive patch testing is not uncommon, but persistent patch test reactions are rarely reported. We present a case of a 53‐year‐old woman with a 7‐year history of a scattered, pruritic papular dermatitis. Patch testing demonstrated a persistent, positive reaction to gold sodium thiosulfate. The histopathology of the patch test site and that of the cutaneous eruption were similar in nature but differing in severity. No other allergens have been identified, but gold avoidance has not yet resulted in the clearing of her eruption. This case underscores the difficulty in making a clinical correlation despite suggestive clinical pathologic evidence.
Presence of formaldehyde in topical corticosteroid preparations available on the Swedish market
Authors: Goon Anthony Teik‐Jin , Gruvberger Birgitta , Persson Lena , Isaksson Marléne , Bruze Magnus
Published: May 2003

The aim of this study was to investigate the formaldehyde content of topical corticosteroid preparations available on the Swedish market. 73 samples were analysed with the chromotropic acid (CA) method for semi‐quantitative formaldehyde determination and 30 samples with a high‐performance liquid chromatographic method. These included 24 ointments, 28 creams, 1 lotion, 6 liniments, 2 gels, 9 solutions, 2 mousses and 1 oral paste. Formaldehyde was found in 5 creams and 1 ointment. Sources of formaldehyde in these preparations were discussed. Isopropanol was identified as a probable source of yellow discoloration, leading to false‐negative results with the CA method.
Liebe und Tabu: Zum Kulturtransfer des Isis‐Osiris‐Mythos in die Moderne: Ingeborg Bachmanns Der Fall Franza und Robert Musils Isis und Osiris
Authors: Jagow Bettina
Published: May 2003

In dem Aufsatz wird der Kulturtransfer des altägyptischen Isis‐Osiris‐Mythos am Beispiel von Robert Musils Gedicht Isis und Osiris und Ingeborg Bachmanns Romanfragment Der Fall Franza diskutiert. Kulturtransfer, so die These der Verfasserin, hat immer dort statt, wo Grenzen überschritten werden und das Transferierte in einen neuen normierten Rahmen transformiert wird. In der Literaturgeschichte wird Transfer exemplarisch mit dem Paradigma von Norm und Normüberschreitung markiert; beispielhaft ist das Oppositionsfeld von Liebe und Tabu. Es ist auch für die beiden untersuchten Texte hinsichtlich des Mythos‐Transfers entscheidend: Während Musils Text in den 1920er Jahren die Bearbeitung des Mythos auf der Folie von Traum und Inzestthematik poetisch variiert, kommt es im Text von Bachmann zu keiner substantiellen Transformation des Mythos. Vielmehr wird er über den Intertext aus Musils Gedicht nur unvollständig zitiert. Durch diese, auch poetologisch zu deutende Arbeit mit dem Isis‐Osiris‐Mythos wirft Bachmanns Text die Diskussion um die Schwierigkeiten eines Fortschreibens alter Bilder und Muster nach 1945 auf; zugleich kann dadurch einer expliziten Dialektik von Norm und Normüberschreitung widersprochen und der Blick auf historisch bedingte Erklärungsmuster kulturellen Transfers gerichtet werden. Mit dieser Perspektive können literarische Texte Aussagen über Kultur treffen und in ihrer Funktion als Metatexte Strukturen von Kultur veranschaulichen.
Periodontal diseases: current and future indications for local antimicrobial therapy
Authors: Trombelli L , Tatakis DN
Published: May 2003

The microbial etiology of gingivitis and periodontitis provides the rationale for use of adjunctive antimicrobial agents in the prevention and treatment of periodontal diseases. Although mechanical removal of supra‐ and subgingival calcified and non‐calcified plaque deposits has been proved effective to control the gingival inflammatory lesions as well as to halt the progression of periodontal attachment loss, some patients may experience additional benefits from the use of systemic or topical antimicrobial agents. Such agents are able to significantly affect supra‐ and subgingival plaque accumulation and/or suppress or eradicate periodontal pathogenic microflora. Currently, properly selected local antiseptic and systemic antibiotic therapies can provide periodontal treatment that is generally effective, low‐risk and affordable. This paper will briefly review the host‐related conditions in which the periodontal preventive and therapeutic approaches may be effectively assisted by a local antimicrobial regimen. Potential future indications for adjunctive local antimicrobial therapy will also be discussed.
Plaque as a biofilm: pharmacological principles of drug delivery and action in the sub‐ and supragingival environment
Authors: Marsh PD
Published: May 2003

Dental plaque is the diverse microbial community, embedded in a matrix of host and bacterial polymers, growing on teeth as a biofilm. Dental plaque develops naturally, and contributes to the host defences by preventing colonization by exogenous species. The composition of dental plaque varies at distinct surfaces as a result of the inherent biological and physical properties at these sites; the balance of the predominant bacterial populations shifts in disease. Plaque has an open architecture, with channels traversing from the biofilm surface through to the enamel. This structure affects the movement of molecules within plaque, and gradients in key determinants develop. Bacteria growing on a surface display a novel phenotype; one consequence of which is an increased resistance to antimicrobial agents. Resistance can result from restricted inhibitor penetration (diffusion‐reaction theory), slower bacterial growth rates, transfer of resistance genes, suboptimal environmental conditions for inhibitor activity, and the expression of a resistant phenotype. Such biofilm‐associated traits, coupled with the pharmacokinetic profile of orally delivered antimicrobial agents (high concentrations for short periods/lower concentrations for longer periods), affect the mode of action and efficacy of antimicrobials. Agents with a broad spectrum of activity in laboratory studies may display a far narrower inhibitory profile under the conditions prevailing in the mouth. This may result in a selective inhibition of species implicated in disease, or reduced production of virulence factors, while preserving the benefits associated with a resident oral microflora.
Systemic antimicrobials in the treatment of chronic periodontal diseases: a dilemma
Authors: Addy M , Martin MV
Published: May 2003

The use of systemic antimicrobials in the treatment of acute and chronic periodontal diseases must be viewed as a dilemma. On the one hand, the approach is attractive because of the microbial nature of periodontal diseases but, on the other hand, evidence of benefit of these agents is equivocal for the majority of periodontal diseases and antimicrobials have the potential to cause harm. The disadvantages of systemic antimicrobials can be grouped under the headings of allergic reactions, superinfection, toxicity, drug interactions, patient compliance and, perhaps of most widespread importance, bacterial resistance. Mechanical debridement methods, including drainage of pus for acute periodontal abscesses, should be considered the first line treatment for most periodontal diseases. Systemic antimicrobials should be considered as adjuncts to mechanical debridement methods and, in chronic disease, never used alone as they can predispose to abscess formation. Adjunctive systemic antimicrobials may be considered in acute disease where debridement or drainage of pus is difficult, where there is local spread or systemic upset. In chronic periodontal diseases, adjunctive antimicrobials should be considered in early onset or rapidly progressive disease or in advanced chronic adult disease where mechanical therapies have failed or surgery is not a preferred option. Inadequate oral hygiene and tobacco smoking are contra‐indications to the use of antimicrobials. The value of systemic antimicrobials, where other systemic risk factors co‐exist, has still to be established. The role of microbial diagnosis and sensitivity testing for antimicrobial selection at this time must be questioned.
Locally delivered antimicrobials for the treatment of chronic periodontitis
Authors: Etienne D
Published: May 2003

The basic treatment of chronic periodontitis is a mechanical debridement of periodontal pockets by scaling and root planing (S/RP) in combination with efficient plaque control. Locally delivered antiseptics (LDA) have been proposed to practitioners and, while subgingival irrigation of antiseptics is still used in clinical practice, the introduction in our therapy of a slow release and subgingival delivery of tetracycline has changed the rationale from a mechanical treatment towards a combined therapy for full mouth/sites disinfection. Various antibiotics, antiseptics and resorbable carriers are now proposed with similar targets to arrest disease progression. In chronic periodontitis, LDA cannot be used routinely in combination with S/RP, because of the limited clinical benefit, even if an increased percentage of deep sites may show an improvement. Prospective multicenter studies considering risk factors for disease progression have to be designed to identify patients who may benefit the most from LDA. For non‐responding sites or recurrent pockets, the controversies are limited, because a combined S/RP and LDA may avoid the need for surgery. However, the patient cost/benefit ratio needs to be estimated as well as adverse effects in particular antibiotics.
Dendritic‐cell‐specific ICAM3‐grabbing non‐integrin is essential for the productive infection of human dendritic cells by mosquito‐cell‐derived dengue viruses
Authors: Navarro‐Sanchez Erika , Altmeyer Ralf , Amara Ali , Schwartz Olivier , Fieschi Franck , Virelizier Jean‐Louis , Arenzana‐Seisdedos Fernando , Desprès Philippe
Published: June 2003

Dengue virus (DV) is a mosquito‐borne flavivirus that causes haemorrhagic fever in humans. DV primarily targets immature dendritic cells (DCs) after a bite by an infected mosquito vector. Here, we analysed the interactions between DV and human‐monocyte‐derived DCs at the level of virus entry. We show that the DC‐specific ICAM3‐grabbing non‐integrin (DC‐SIGN) molecule, a cell‐surface, mannose‐specific, C‐type lectin, binds mosquito‐cell‐derived DVs and allows viral replication. Conclusive evidence for the involvement of DC‐SIGN in DV infection was obtained by the inhibition of viral infection by anti‐DC‐SIGN antibodies and by the soluble tetrameric ectodomain of DC‐SIGN. Our data show that DC‐SIGN functions as a DV‐binding lectin by interacting with the DV envelope glycoprotein. Mosquito‐cell‐derived DVs may have differential infectivity for DC‐SIGN‐expressing cells. We suggest that the differential use of DC‐SIGN by viral envelope glycoproteins may account for the immunopathogenesis of DVs.
Combined treatment of Bcl‐2 antisense oligodeoxynucleotides (G3139), p‐glycoprotein inhibitor (PSC833), and sterically stabilized liposomal doxorubicin suppresses growth of drug‐resistant growth of drug‐resistant breast cancer in severely combined immunodeficient mice
Authors: Lopes de Menezes Daniel E. , Hu Yanping , Mayer Lawrence D.
Published: May 2003

We studied the possibility of increasing sensitization of drug‐resistant MDA435/LCC6 multidrug‐resistant (MDR) human breast cancer cells to doxorubicin (DOX) by increasing cellular drug retention with P‐glycoprotein (P‐gp) inhibitor PSC833 in combination with induction of cell death through down‐regulation of Bcl‐2 protein using Bcl‐2 antisense (G3139). In in vitro cytotoxicity assays, the combination of G3139 with DOX exhibited 40% increased cytotoxicity in both wild‐type (WT) and MDR cells. PSC833 increased the cytotoxicity of DOX and Taxol with complete and partial reversal of the resistance of MDR cells to DOX and Taxol, respectively. The presence of G3139 did not increase the cytotoxicity of PSC833 combined with DOX or Taxol in both cell lines. In vivo studies with WT and MDR cell lines transplanted into severely combined immunodeficient mice demonstrated that G3139 (5 mg/kg) was able to suppress the growth of both WT and MDR tumors to an equivalent extent. PSC833 (100 mg/kg) partially restored the sensitivity of resistant tumors to DOX, and the combination of G3139 and PSC833 with liposomal DOX showed maximum growth suppression of MDR tumors compared with individual treatments. The improved efficacy of this treatment was attributed to Bcl‐2 antisense‐induced apoptosis, combined with cellular retention of DOX in tumor cells via P‐gp blockade.
One‐week triple therapy with esomeprazole, clarithromycin and metronidazole provides effective eradication of Helicobacter pylori infection
Authors: Veldhuyzen Van Zanten S. , Machado S. , Lee J.
Published: June 2003

Aim: To compare the eradication rates of treatment with esomeprazole, metronidazole and clarithromycin (EMC) vs. omeprazole, metronidazole and clarithromycin (OMC), given for 7 days. OMC treatment was followed by 3 weeks of treatment with 20 mg omeprazole alone; the EMC group received placebo.

Methods: A randomized, double‐blind, controlled study was conducted in 36 Canadian centres. Patients had a minimum 3‐month history of dyspepsia, with or without a previous history of peptic ulcer disease, and were Helicobacter pylori positive by urea breath test. The eradication of H. pylori was determined by two negative breath tests performed at least 4 and 8 weeks following the completion of treatment.

Results: The intention‐to‐treat and per protocol populations consisted of 379 and 339 patients, respectively. The success rates of EMC/placebo were 76% (144/190) by intention‐to‐treat and 80% (138/172) by per protocol analysis; for OMC/omeprazole, the rates were 72% (137/189) and 75% (125/167), respectively. The difference between the two treatment groups was not significant. Treatment was well tolerated.

Conclusions: A 7‐day regimen of esomeprazole, metronidazole and clarithromycin is effective and well tolerated for the eradication of H. pylori infection.
Review article: the treatment of refractory Helicobacter pylori infection
Authors: Mégraud F. , Lamouliatte H.
Published: June 2003

The occurrence of refractory Helicobacter pylori infection is increasing. When the bacteria are not eradicated it means that the antibiotics have not reached the gastric mucosa at a sufficient concentration and over a sufficient time lapse to kill them. The main reasons for this are poor patient compliance, resistant bacteria, low gastric pH and a high bacterial load. Therefore, when administering a new treatment, it is important to choose antibiotics which do not face resistance problems and which increase the dosage of antisecretory drugs and the duration of treatment and, if possible, to add a topical agent such as bismuth salt.

The recommended empirical strategy is to prescribe quadruple therapy or, alternatively, 2‐week triple therapy including amoxicillin–metronidazole, tetracycline–metronidazole or amoxicillin–rifabutin. However, when H. pylori is susceptible, clarithromycin can still be used. In the case of a high level of metronidazole resistance, furazolidone can be employed. In each case, it is important to ensure good patient compliance, and counselling is helpful in this regard. However, the best approach remains the prevention of refractory H. pylori infection and, for this purpose, antimicrobial susceptibility testing before first‐line therapy is important and should be encouraged.
Impact of structural and autocyclic basin‐floor topography on the depositional evolution of the deep‐water Valparaiso forearc basin, central Chile
Authors: Laursen Jane , Normark William R.
Published: May 2003

The Valparaiso Basin constitutes a unique and prominent deep‐water forearc basin underlying a 40‐km by 60‐km mid‐slope terrace at 2.5‐km water depth on the central Chile margin. Seismic‐reflection data, collected as part of the CONDOR investigation, image a 3–3.5‐km thick sediment succession that fills a smoothly sagged, margin‐parallel, elongated trough at the base of the upper slope. In response to underthrusting of the Juan Fernández Ridge on the Nazca plate, the basin fill is increasingly deformed in the seaward direction above seaward‐vergent outer forearc compressional highs. Syn‐depositional growth of a large margin‐parallel monoclinal high in conjunction with sagging of the inner trough of the basin created stratal geometries similar to those observed in forearc basins bordered by large accretionary prisms. Margin‐parallel compressional ridges diverted turbidity currents along the basin axis and exerted a direct control on sediment depositional processes. As structural depressions became buried, transverse input from point sources on the adjacent upper slope formed complex fan systems with sediment waves characterising the overbank environment, common on many Pleistocene turbidite systems. Mass failure as a result of local topographic inversion formed a prominent mass‐flow deposit, and ultimately resulted in canyon formation and hence a new focused point source feeding the basin.

The Valparaiso Basin is presently filled to the spill point of the outer forearc highs, causing headward erosion of incipient canyons into the basin fill and allowing bypass of sediment to the Chile Trench. Age estimates that are constrained by subduction‐related syn‐depositional deformation of the upper 700–800 m of the basin fill suggest that glacio‐eustatic sea‐level lowstands, in conjunction with accelerated denudation rates, within the past 350 ka may have contributed to the increase in simultaneously active point sources along the upper slope as well as an increased complexity of proximal depositional facies.
Cytotoxic drugs enhance the ex vivo sensitivity of malignant cells from a subset of acute myeloid leukaemia patients to apoptosis induction by tumour necrosis factor receptor‐related apoptosis‐inducing ligand
Authors: Jones Dylan T. , Ganeshaguru Kanagasabai , Mitchell Wayne A. , Foroni Letizia , Baker Robert J. , Prentice H. Grant , Mehta Atul B. , Wickremasinghe R. Gitendra
Published: May 2003

Summary. We have studied the actions of tumour‐necrosis‐factor‐related apoptosis‐inducing ligand (TRAIL) on cells isolated from patients with acute myeloid leukaemia (AML). Apoptosis induction was initially assessed by quantitative morphological analysis. Only 2/19 isolates showed a > 10% increase in apoptotic cells following TRAIL treatment. However, incubation with TRAIL combined with fludarabine, cytosine arabinoside or daunorubicin resulted in additive or super‐additive apoptosis induction in approximately half of the isolates. Molecular evidence of super‐additive apoptosis induction by TRAIL and cytotoxic agents was obtained by quantification of caspase 3 activation, detected by Western blot analysis of poly (ADP ribose) polymerase cleavage. The ability of TRAIL and daunorubicin to induce super‐additive apoptosis correlated with the ability of these agents to activate caspase 8 and to augment cellular levels of the truncated pro‐apoptotic form of the BCL‐2 family member BID. Our data suggest that co‐administration of TRAIL with conventional cytotoxic drugs may be of therapeutic value in some patients with AML.
P‐glycoprotein and BCL‐2 levels predict outcome in adult acute lymphoblastic leukaemia
Authors: Del Principe Maria Ilaria , Del Poeta Giovanni , Maurillo Luca , Buccisano Francesco , Venditti Adriano , Tamburini Anna , Bruno Antonio , Cox Maria Christina , Suppo Giovanna , Tendas Andrea , Giannì Laura , Postorino Massimiliano , Masi Mario , Del Principe Domenico , Amadori Sergio
Published: May 2003

Summary. Concurrent resistance mechanisms, such as P‐glycoprotein (PGP) and bcl‐2, may contribute to a worse outcome in adult acute lymphoblastic leukaemia (ALL). Between 1990 and 2000, we analysed PGP and bcl‐2 by flow cytometry, using two anti‐PGP (C219 and JSB‐1) monoclonal antibodies (mAbs) and an anti‐bcl‐2 mAb in 115 de novo adult ALL patients. Both a longer overall survival (OS) and longer disease‐free survival (DFS) were observed in PGP‐negative patients (23%vs 0% at 3 years, P = 0·011 and 29%vs 0% at 2 years, P = 0·006 for C219 respectively; 42%vs 0% at 1·5 years, P = 0·004 and 53%vs 0% at 8·5 months, P = 0·00006 for JSB‐1 respectively). Bcl‐2 positivity was associated with a significantly higher complete remission rate (90%vs 66%, P = 0·01). Moreover, in 69 patients not presenting with either t(9;22) or B‐mature immunophenotype, PGP negativity (JSB‐1) maintained its significant favourable prognostic impact with regard to OS (41%vs 0% at 1·5 years, P = 0·009) and DFS (83%vs 0% at 6 months, P = 0·0005). Importantly, within a subset of 62 patients with normal (n = 31) or unknown (n = 31) karyotype, PGP (JSB‐1)‐negative patients showed both a significantly longer OS and DFS (63%vs 0% at 1·4 years, P = 0·018 and 84%vs 0% at 6 months, P = 0·001 respectively). In multivariate analysis, JSB‐1 (P = 0·008) and cytogenetics (P = 0·02) were found to be independent prognostic factors with regard to DFS. Therefore, in adult ALL, PGP and bcl‐2 represent sensitive indicators of clinical outcome, and potential targets of novel molecules aimed at overcoming chemoresistance and recurrent relapses.
Growth regulation by p27Kip1 is abrogated by multiple mechanisms in aggressive malignant lymphomas
Authors: Lin Zhaosheng , Lim Steve , Lim Megan S.
Published: May 2003

Summary. The cyclin‐dependent kinase inhibitor p27Kip1 is a key regulator of the G1/S transition, and an inverse relationship between p27Kip1 protein expression and proliferation index has been reported in malignant lymphomas. However, a subset of aggressive B‐cell lymphomas demonstrates high p27Kip1 expression despite a high proliferation index. The aim of this study was to determine potential mechanisms by which lymphoma cells abrogate the growth inhibitory effect of high p27Kip1. The effect of transforming growth factor‐β (TGF‐β) and serum stimulation on p27Kip1 expression and cyclin E/cdk2 activity was investigated in four lymphoma cell lines, Jurkat, CEM‐6, OCI‐Ly1 and Nalm‐6. Reactive lymphocytes responded to growth inhibitory TGF‐β by inducing p27Kip1 expression, with subsequent accumulation of cells in G0/G1. In contrast, TGF‐β did not alter the level of p27Kip1 in Jurkat, CEM‐6 and OCI‐Ly1 cells with no change in cyclin E/cdk2‐kinase activity. Serum stimulation also did not result in a significant change in p27Kip1 expression. Western blot analysis of subcellular fractions demonstrated cytoplasmic p27Kip1, corroborated by immunocytochemistry in a subset of the lymphoma cells. Sequestration of p27Kip1 by cyclin D3 was observed in the nuclear and cytoplasmic fractions of Nalm‐6, OCI‐Ly‐1 and NCEB cells. These results indicate that multiple mechanisms contribute to the abrogation of growth regulation by unscheduled high p27Kip1 protein expression including deficient response to TGF‐β and serum, sequestration by cyclin D3 and cytoplasmic displacement.
Common cytological and cytogenetic features of Epstein‐Barr virus (EBV)‐positive natural killer (NK) cells and cell lines derived from patients with nasal T/NK‐cell lymphomas, chronic active EBV infection and hydroa vacciniforme‐like eruptions
Authors: Zhang Yu , Nagata Hiroshi , Ikeuchi Tatsuro , Mukai Hiroyuki , K. Oyoshi Michiko , Demachi Ayako , Morio Tomohiro , Wakiguchi Hiroshi , Kimura Nobuhiro , Shimizu Norio , Yamamoto Kohtaro
Published: May 2003

Summary. In this study, we describe the cytological and cytogenetic features of six Epstein‐Barr virus (EBV)‐infected natural killer (NK) cell clones. Three cell clones, SNK‐1, ‐3 and ‐6, were derived from patients with nasal T/NK‐cell lymphomas; two cell clones, SNK‐5 and ‐10, were isolated from patients with chronic active EBV infection (CAEBV); and the other cell clone, SNK‐11, was from a patient with hydroa vacciniforme (HV)‐like eruptions. An analysis of the number of EBV‐terminal repeats showed that the SNK cell clones had monoclonal EBV genomes identical to the original EBV‐infected cells of the respective patients, and SNK cells had the type II latency of EBV infection, suggesting that not only the cell clones isolated from nasal T/NK‐cell lymphomas but also those isolated from CAEBV and HV‐like eruptions had been transformed by EBV to a certain degree. Cytogenetic analysis detected deletions in chromosome 6q in five out of the six SNK cell clones, while 6q was not deleted in four control cell lines of T‐cell lineage. This suggested that a 6q deletion is a characteristic feature of EBV‐positive NK cells, which proliferated in the diseased individuals. The results showed that EBV‐positive NK cells in malignant and non‐malignant lymphoproliferative diseases shared common cytological and cytogenetic features.
Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population‐based study of incidence and survival
Authors: Passmore S. Jane , Chessells Judith M. , Kempski Helena , Hann Ian M. , Brownbill Pat A. , Stiller Charles A.
Published: May 2003

Summary.  We aimed to identify and classify cases of paediatric myelodysplastic syndromes (MDS) occurring in Britain to estimate the incidence of this rare group of diseases, investigate the results of therapy and identify prognostic risk factors. Patients aged below 15 years at diagnosis were collected from England, Scotland and Wales, inclusively between 1990 and 1999. One hundred and thirty‐five patients were accepted as de novo MDS or juvenile myelomonocytic leukaemia (JMML). The incidence for this period was 1·35 per million (age standardized rate) which is below that reported outside the UK. The overall survival was 45%[standard error (SE) = 4%] at 5 years: 40% (SE = 6%) for JMML and 50% (SE = 6%) for other MDS. Significant adverse prognostic factors for JMML were a platelet count < 40 × 109/l, raised fetal haemoglobin, FPC score and age above 2 years at diagnosis, for other MDS only monosomy 7 was significant. To conclude, the incidence of MDS/JMML in children in the UK appears to be lower than that reported outside the UK. This may be either a real difference in incidence or variation in reporting. Monosomy 7 is associated with poor outcome in MDS other than JMML. The prognosis of JMML depends on age, platelet count and fetal haemoglobin.
Bone mineral density outcomes following long‐term treatment with subcutaneous testosterone pellet implants in male hypogonadism
Authors: Zacharin Margaret R. , Pua Joseph , Kanumakala Shankar
Published: June 2003

background Osteoporosis is a common complication of untreated male hypogonadism. Even mild hypogonadism due to suboptimal testosterone replacement may result in decreased bone mineralization and osteoporosis.

objective To assess bone mineral density in hypogonadal men following long‐term long‐acting subcutaneous testosterone pellet implants as replacement therapy.

patients A cross‐sectional study of 37 patients with primary or secondary hypogonadism receiving long‐term (mean 6·6 years) subcutaneous testosterone pellet implants as replacement therapy.

measurements Bone mineral density was measured in all patients using dual energy X‐ray absorptiometry. Serum testosterone 3–4 months after insertion of pellets was measured in all patients to assess adequacy of replacement therapy.

results Mean areal bone mineral density were 1·02 (SD 0·14) g/cm2 with a mean Z score of −0·64 (SD 1·3) and 0·87 (SD 0·13) g/cm2 with a mean Z score of −0·72 (SD 1·2) at lumbar spine and neck of femur, respectively. Mean serum testosterone 3–4 months after pellets insertion was 15·45 nmol/l (SD 4·2 nmol/l). There was no significant correlation between bone mineral density and patient's age at start or duration of testosterone therapy.

conclusions Bone mineral density in long‐term regularly treated hypogonadal men was not different from the age‐matched reference range for normal men. Long‐acting subcutaneous testosterone pellet implants as replacement therapy in male hypogonadism are safe, acceptable to the patient, result in adequate bone mass accumulation and maintenance of normal bone mineral density. By provision of sustained physiological levels of testosterone they may contribute to increased androgen effect at the receptor level.
Hereditary corticosteroid‐binding globulin deficiency due to a missense mutation (Asp367Asn, CBG Lyon) in a Brazilian kindred
Authors: Brunner Elisa , Baima Jader , Vieira Teresa C. , Vieira José G. H. , Abucham Julio
Published: June 2003

objective Abnormal corticosteroid‐binding globulin (CBG) is an extremely rare condition and only three mutations have been described in four families. The molecular basis of an abnormal CBG in a Brazilian family was studied and correlations between genotype and serum cortisol, cortisol binding capacity (CBC) and CBG levels were determined.

subjects All 10 family members, comprising three generations, and nine healthy volunteers were studied.

measurements Genomic DNA was extracted from white blood cells from all family members. The human cbg exons 2–5 were amplified by PCR, submitted to automatic sequencing. Cortisol and CBG levels in serum were measured by radioimmunoassay (RIA). CBC in serum was determined using tritiated cortisol and other cortisol binding parameters were calculated through Scatchard analysis.

results A missense mutation in exon 5 of cbg (1254G → A; Asp367Asn), recently described as CBG Lyon, was found in all family members. The proband and one sister were homozygous whereas all other family members, including parents, were heterozygous for this mutation. Cortisol levels in the only two homozygotes were lower than in heterozygotes and both were significantly lower as compared to controls (69 and 182 nmol/l vs. 267 ± 129 nmol/l vs. 459 ± 195 nmol/l, respectively, P < 0·05). CBC was decreased in the two homozygotes as compared to heterozygotes and in both groups as compared to controls (< 90 and 114 nmol/l vs. 305·0 ± 81·4 nmol/l vs. 594·8 ± 59·5 nmol/l, respectively, P < 0·05). CBG levels were lower in homozygotes as compared to heterozygotes and in both as compared to controls (325 and 375 nmol/l vs. 496·75 ± 50·75 nmol/l vs. 647·25 ± 87·50 nmol/l, respectively, P < 0·05).

conclusions An abnormal CBG resulting from a missense mutation and known as CBG Lyon was found in this Brazilian kindred. This abnormal CBG has decreased affinity for cortisol and results in low or low normal serum cortisol levels in homozygous and heterozygous subjects. Although relative hypotension and fatigue have recently been associated with CBG deficiency in a family with two CBG mutations (null and Lyon), the two homozygous subjects in this kindred were both normotensive and only the proband presented with fatigue.