bluuebunny/crossref_metadata_2025 huggingface dataset:
An InGaN-based horizontal-cavity surface-emitting laser diode
Authors: Akasaka Tetsuya , Nishida Toshio , Makimoto Toshiki , Kobayashi Naoki
Published: May 2004

An InGaN-based horizontal-cavity surface-emitting laser diode (HCSELD) was fabricated by dry-etching of an InGaN-based multilayer on a SiC substrate and selective-area regrowth of a Mg-doped GaN layer. The InGaN-based HCSELD is a Fabry–Perot laser diode equipped with outer micromirrors that reflect the laser beams upward. The cavity mirrors and outer micromirrors are vertical {112̄0} and inclined {112̄2} facets of the regrown Mg-doped GaN layers, respectively. These grown facets are very smooth and had little angle misalignment. The InGaN-based HCSELD lased by current injection at room temperature. Current-injection lasing for group-III-nitride-based surface-emitting lasers is reported.
Temporal variation in photoluminescence from single InGaN quantum dots
Authors: Rice James H. , Robinson James W. , Jarjour Anas , Taylor Robert A. , Oliver Rachel A. , Briggs G. Andrew D. , Kappers Menno J. , Humphreys Colin J.
Published: May 2004

We report measurements of optical transitions in single III/V (InGaN) quantum dots as a function of time. Temporal fluctuations in microphotoluminescence peak position and linewidth are demonstrated and attributed to spectral diffusion processes. The origin of this temporal variation is ascribed to randomly generated local electric fields inducing a Stark shift in the optical emission peaks of the InGaN quantum dots.
Reduction of leakage current by Co doping in Pt/Ba0.5Sr0.5TiO3/Nb–SrTiO3 capacitor
Authors: Wang S. Y. , Cheng B. L. , Wang Can , Dai S. Y. , Lu H. B. , Zhou Y. L. , Chen Z. H. , Yang G. Z.
Published: May 2004

Effect of Co doping on leakage current has been investigated in capacitor consisting of Ba0.5Sr0.5Ti1−xCoxO3 (BSTC, x=0, 0.002, 0.010) thin film, Pt top electrode, and Nb-doped SrTiO3 (STON) bottom electrode. Co doping remarkably decreases the leakage current in BSTC thin film, such as from 9×10−7 A in undoped thin film to 8×10−11 A in 1.0 at. % Co-doped BSTC thin film at bias voltage of 6 V. In the case of the Pt electrode positively biased, the leakage current shows space-charge-limited-current behavior. The trap-filled-limit voltage and the calculated trapped electron density increase with Co concentration in BSTC thin film. The mechanism of the reduction of the leakage current by Co doping is discussed.
Aracyl Triflates as Derivatizing Agents for Biological Betaines
Authors: Happer D. Alan R. , Hayman Colin M. , Storer Malina K. , Lever Michael
Published: May 2004

Several trifluoromethanesulfonates of general structure ArCOCH2OTf were prepared and their suitability for use as derivatizing agents for the HPLC analysis of betaines was assessed. Four of them (Ar = 2′-naphthyl, 2′-fluorenyl, 6′-methoxynaphthacyl, and 2′-phenanthrenacyl) showed promise for use with UV and/or fluorescence detectors, with the last potentially the most promising.
Non-CNS Acting Opiates Bearing Guanidino Substituents
Authors: Subasinghe Kamani R. , Jackson W. Roy , Young Jacqui F. , Papanastasiou Maria , Jarrott Bevyn
Published: May 2004

A series of guanidino-substituted opiates based on morphine, diprenorphine, and buprenorphine have been synthesized. Guanidines with aryl and alkyl substituents as well as unsubstituted ones have been attached to the opiate nucleus with spacer units of varying length. The spacer groups have mainly been attached to the opiates via the opiate nitrogen atom. A few compounds involving attachment through opiate oxygen atoms have been prepared, but were found to be ineffective as analgesics.The activity of the compounds as analgesics has been evaluated using the phenylquinone (PQ) abdominal-constriction test and their ability to enter the CNS evaluated with the Straub tail response. The compounds most active in the PQ abdominal-constriction test and showing no Straub tail behaviour contained aryl-substituted guanidines.
Octahedral Complexes of a Mixed N,N,O-Donor Ligand N-trans-(2'-hydroxycyclohexyl)-2-aminomethylpyridine
Authors: Robertson Mark J. , Lawrance Geoffrey A. , Maeder Marcel , Turner Peter
Published: May 2004

The unsymmetric mixed-donor Nam,Npy,O-ligand N-trans-(2'-hydroxycyclohexyl)-2-aminomethylpyridine (pyca, 1) was readily prepared by reaction of an epoxide (cyclohexene oxide) with (2-aminomethyl)pyridine. The ligand forms octahedral bis-tridentate complexes, exemplified with isolation of copper(II), nickel(II), zinc(II), and cobalt(III) compounds; in addition, a square-planar palladium(II) complex with the ligand behaving as bidentate was prepared. The bis-tridentate octahedral complexes may exist in six geometric isomeric forms, and molecular mechanics analysis was employed to predict the most stable isomer for copper(II), nickel(II), and cobalt(III) complexes. For the copper(II) and cobalt(III) complexes, the predictions match the X-ray crystal structures of the single isomer isolated in each case. Both the copper(II) complex [Cu . 12](ClO4)2 and the cobalt(III) complex [Co . 1 . (1–H)](ClO4)2 crystallized in the monoclinic space group P21/n (no. 14), with a 9.8400(13), b 15.434(2), c 10.0180(13) Å, and β 109.004(2)°, and a 14.162, b 18.583, c 21.596 Å, and β 100.04°, respectively. Both complexes adopt distorted octahedral structures. The copper(II) complex exists as the all-trans-fac isomer with Jahn–Teller elongation of the Cu–O bond [2.3795(19) Å] compared to Cu–Npy [2.040(2) Å] and Cu–Nam [2.024(2) Å] distances. The cobalt(III) complex appears as the cis,cis,trans(Npy) fac isomer, but deprotonation of one of the two alcohol groups leads to all six M–L distances differing: for each of two similar independent complex cations, Co–O [e.g. 1.9123(16), 1.9459(16) Å], Co–Nam [e.g. 1.949(2), 1.968(2) Å], and Co–Npy [e.g. 1.938(2), 1.940(2) Å] vary, with particularly the deprotonated alcohol bond significantly shorter than the protonated bond, despite a strong hydrogen bonding interaction with the protonated alcohol in the partner complex cation in the unit cell.
The Synthesis of a D-Glucose-like Piperidin-2-one: Isofagomine Lactam
Authors: Macdonald James M. , Stick Robert V.
Published: May 2004

Benzyl 4-cyano-4-deoxy-α-D-arabinoside was converted into both its2,3-di-O-acetyl and 2,3-di-O-(tert-butyldimethylsilyl)derivatives. The latter, by a process of hydrogenolysis, oxidation, and methanolysis, gave methyl2,3-di-O-(tert-butyldimethylsilyl)-4-cyano-4-deoxy-D-arabinonate. Reductionof this methyl ester with borane dimethyl sulfide gave, after deprotection, isofagomine lactam.
Stereoselective Synthesis of the Hydrophobic Side Chain of Scyphostatin
Authors: Takagi Ryukichi , Tsuyumine Shinjiro , Nishitani Hiroko , Miyanaga Wataru , Ohkata Katsuo
Published: May 2004

The hydrophobic side chain of scyphostatin was synthesized by a convergent synthetic pathway. The key reactions were the enzymatic asymmetric acetylation of a meso-diol, construction of the C12′–C13′ trisubstituted E-olefin moiety by Negishi coupling, and construction of the (2′E,4′E ,E,6′E)-triene moiety by Horner–Wadsworth–Emmons olefination.
The Challenges with Substance Databases and Structure Search Engines
Authors: Cooke Helen , Ridley Damon D.
Published: May 2004

Structure connection tables, which are commonly used for the representation of chemical structures in electronic databases, are valuable for substances where specific valence bond structures are known or can be drawn. How-ever there are many classes of substances (for example alloys, catenanes, polymers, or salts) which cannot be fully represented by valence bond structures. There are also issues of definition (such as when a substance is a co-ordination compound, or hydrate, or salt), and of bonding types (resonance, donor complexes, π-complexes). Producers of chemical substance databases may address these issues in different ways and generally need to introduce concepts (for example multicomponent substances) with which chemical scientists may not be familiar. In addition to these aspects of database content, the searcher needs to understand the algorithms behind the structure search engines. For example, the SciFinder search engine has considerable in-built chemical intelligence at the initial search level and then has many tools to mine the data once obtained; the CrossFire search engine also employs several algorithms by default and allows further options to vary them.
Difference in Conformation of Virginiamycin M1 in Chloroform and Bound Form in the 50S Ribosome or Streptogramin Acetyltransferase
Authors: Dang Jason , Bergdahl B. Mikael , Separovic Frances , T. C. Brownlee Robert , P. Metzger Robert
Published: May 2004

The conformation of virginiamycin M1 (VM1) in chloroform, determined by high-resolution NMR experiments, differs significantly from that of the X-ray crystal structure of VM1 bound to the 50S ribosome and to the active site of a streptogramin acetyltransferase enzyme. This implies that the binding process to these entities causes a major change in VM1 conformation.
A revision of Australian and New Zealand Tethya (Porifera : Demospongiae) with a preliminary analysis of species-groupings
Authors: Sarà Michele , Sarà Antonio
Published: May 2004

Australian and New Zealand Tethya Lamarck, 1814 species have been revised on the basis of museum material and new findings. Ten new species: T. acuta, T. burtoni, T. dendyi, T. expansa, T. flexuosa, T. gunni, T.�hooperi, T. pulitzeri, T. stellodermis and T. tasmaniae are described. Tethya gigantea (von Lendenfeld, 1888), here recognised as a valid species, and T. magna Kirkpatrick, 1903, hitherto known only from South Africa, are redescribed. New observations and taxonomic remarks have been provided for: T. bergquistae, T. corticata, T.�deformis, T. inflata, T. phillipensis, T. ingalli, T. laevis, T. monstrosa, T. orphei, T. robusta, T. seychellensis and T.�tuberculata. The revised species list includes 31 valid species, most of which are endemic to Australia or New Zealand. Species-groups within the genus were investigated using cluster analysis and multidimensional scaling.
Temporal and regional differences in the olfactory proteome as a consequence of MeCP2 deficiency
Authors: Matarazzo Valéry , Ronnett Gabriele V.
Published: May 2004

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the gene encoding
MeCP2.
By binding to methylated CpG dinucleotide promoter regions, MeCP2 acts as a transcriptional repressor, predicting that its absence might result in widespread aberrant gene transcription, leading to the RTT phenotype. Considering this potentially broad action of MeCP2 on expression and the complexity of the brain, especially during development, we approached the consequences of MeCP2 deficiency in a mouse model by using a temporal and regional proteomic strategy. We used the olfactory system (olfactory epithelium and bulb) because its attributes make it an excellent developmental model system. We find evidence of temporal and regional proteomic pattern differences between WT and MeCP2-deficient mice. It was possible to segregate these changes in protein expression into five biological function groups: cytoskeleton arrangement, chromatin modeling, energy metabolism, cell signaling, and neuroprotection. By combining the proteomic results with the RNA levels of the identified proteins, we show that protein expression changes are the consequence of differences in mRNA level or posttranslational modifications. We conclude that brain regions and ages must be carefully considered when investigating MeCP2 deficiency, and that not only transcription should be taken into account as a source for these changes, but posttranslational protein modifications as well.
Reconstitution of retroviral fusion and uncoating in a cell-free system
Authors: Narayan Shakti , Young John A. T.
Published: May 2004

The molecular events underlying the immediate steps of retroviral uncoating, occurring after membrane fusion and leading to the formation of an active reverse transcription complex, are not known. To better understand these processes, we have developed a cell-free system that recapitulates these early steps of retroviral replication by using avian sarcoma and leukosis virus as a model retrovirus. The substrates used in this system are viral particles that are trapped before completing membrane fusion. These virions are induced to fuse out of endosomes and the viral cores are released into solution where they are amenable to biochemical manipulation. This system revealed that membrane fusion is not sufficient to stimulate the formation of a reverse transcription complex. Instead, ATP hydrolysis and cellular factors >5 kDa in size are required. Furthermore, later steps of avian sarcoma and leukosis virus reverse transcription were stimulated by nuclear factors. The cell-free system should now allow for the definition of retroviral uncoating mechanisms and facilitate the identification and characterization of the cellular factors involved.
Translocation and cleavage of myocardial dystrophin as a common pathway to advanced heart failure: A scheme for the progression of cardiac dysfunction
Authors: Toyo-Oka Teruhiko , Kawada Tomie , Nakata Jumi , Xie Han , Urabe Masashi , Masui Fujiko , Ebisawa Takashi , Tezuka Asaki , Iwasawa Kuniaki , Nakajima Toshiaki , Uehara Yoshio , Kumagai Hiroyuki , Kostin Sawa , Schaper Jutta , Nakazawa Mikio , Ozawa Keiya
Published: May 2004

Advanced heart failure (HF) is the leading cause of death in developed countries. The mechanism underlying the progression of cardiac dysfunction needs to be clarified to establish approaches to prevention or treatment. Here, using TO-2 hamsters with hereditary dilated cardiomyopathy, we show age-dependent cleavage and translocation of myocardial dystrophin (Dys) from the sarcolemma (SL) to the myoplasm, increased SL permeability
in situ
, and a close relationship between the loss of Dys and hemodynamic indices. In addition, we observed a surprising correlation between the amount of Dys and the survival rate. Dys disruption is not an epiphenomenon but directly precedes progression to advanced HF, because long-lasting transfer of the missing δ-
SG
gene to degrading cardiomyocytes
in vivo
with biologically nontoxic recombinant adenoassociated virus (rAAV) vector ameliorated all of the pathological features and changed the disease prognosis. Furthermore, acute HF after isoproterenol toxicity and chronic HF after coronary ligation in rats both time-dependently cause Dys disruption in the degrading myocardium. Dys cleavage was also detected in human hearts from patients with dilated cardiomyopathy of unidentified etiology, supporting a scheme consisting of SL instability, Dys cleavage, and translocation of Dys from the SL to the myoplasm, irrespective of an acute or chronic disease course and a hereditary or acquired origin. Hereditary HF may be curable with gene therapy, once the responsible gene is identified and precisely corrected.
Formicine ants: An arthropod source for the pumiliotoxin alkaloids of dendrobatid poison frogs
Authors: Saporito Ralph A. , Garraffo H. Martin , Donnelly Maureen A. , Edwards Adam L. , Longino John T. , Daly John W.
Published: May 2004

A remarkable diversity of bioactive lipophilic alkaloids is present in the skin of poison frogs and toads worldwide. Originally discovered in neotropical dendrobatid frogs, these alkaloids are now known from mantellid frogs of Madagascar, certain myobatrachid frogs of Australia, and certain bufonid toads of South America. Presumably serving as a passive chemical defense, these alkaloids appear to be sequestered from a variety of alkaloid-containing arthropods. The pumiliotoxins represent a major, widespread, group of alkaloids that are found in virtually all anurans that are chemically defended by the presence of lipophilic alkaloids. Identifying an arthropod source for these alkaloids has been a considerable challenge for chemical ecologists. However, an extensive collection of neotropical forest arthropods has now revealed a putative arthropod source of the pumiliotoxins. Here we report on the presence of pumiliotoxins in formicine ants of the genera
Brachymyrmex
and
Paratrechina
, as well as the presence of these ants in the stomach contents of the microsympatric pumiliotoxin-containing dendrobatid frog,
Dendrobates pumilio
. These pumiliotoxins are major alkaloids in
D. pumilio
, and
Brachymyrmex
and
Paratrechina
ants now represent the only known dietary sources of these toxic alkaloids. These findings further support the significance of ant-specialization and alkaloid sequestration in the evolution of bright warning coloration in poison frogs and toads.
Floral homeotic genes are targets of gibberellin signaling in flower development
Authors: Yu Hao , Ito Toshiro , Zhao Yuanxiang , Peng Jinrong , Kumar Prakash , Meyerowitz Elliot M.
Published: May 2004

Gibberellins (GAs) are a class of plant hormones involved in the regulation of flower development in
Arabidopsis
. The GA-deficient
ga1
-
3
mutant shows retarded growth of all floral organs, especially abortive stamen development that results in complete male sterility. Until now, it has not been clear how GA regulates the late-stage development of floral organs after the establishment of their identities within floral meristems. Various combinations of null mutations of DELLA proteins can gradually rescue floral defects in
ga1
-
3
. In particular, the synergistic effect of
rga
-
t2
and
rgl2
-
1
can substantially restore flower development in
ga1
-
3
. We find that the transcript levels of floral homeotic genes
APETALA3
(
AP3
),
PISTILLATA
(
PI
), and
AGAMOUS
(
AG
) are immediately upregulated in young flowers of
ga1
-
3
upon GA treatment. Using a steroid-inducible activation of RGA, we further demonstrated that these floral homeotic genes are transcriptionally repressed by RGA activity in young flowers whereas the expression of
LEAFY
(
LFY
) and
APETALA1
(
AP1
) is not substantially affected. In addition, we observed the partial rescue of floral defects in
ga1
-
3
by overexpression of
AG
. Our results indicate that GA promotes the expression of floral homeotic genes by antagonizing the effects of DELLA proteins, thereby allowing continued flower development.
The Costs of Price Stability: Downward Nominal Wage Rigidity in Europe
Authors: Holden Steinar
Published: May 2004

In most European countries, the prevailing terms of employment, including the nominal wage, can be changed only by mutual consent. This legal feature gives workers a strategic advantage in wage negotiations when employers push for a nominal wage cut. The upshot is a long‐run trade‐off between inflation and unemployment for low levels of inflation, in spite of all agents being rational and with no expectational errors. Specifically, downward nominal wage rigidity and excess unemployment at zero inflation are related to three factors: the coverage of collective agreements, the legal framework at contract renewal, and the strictness of the employment protection legislation for non‐union workers.
Modelling Monetary Policy: Inflation Targeting in Practice
Authors: Martin Christopher , Milas Costas
Published: May 2004

This paper estimates a simple structural model of monetary policy in the UK focusing on the policy of inflation targeting introduced in 1992. We find that: (i) the adoption of inflation targeting led to significant changes in monetary policy; (ii) post‐1992 monetary policy is asymmetric as policy‐makers respond more to upward deviation of inflation away from the target; (iii) post‐1992 policy‐makers may be attempting to keep inflation within the 1.4%–2.6% range rather than pursuing a point target of 2.5% and (iv) the response of monetary policy to inflation is nonlinear as interest rates respond more when inflation is further from the target.
What Lies Behind Income Mobility? Reranking and Distributional Change in Belgium, Western Germany and the USA
Authors: Van Kerm Philippe
Published: May 2004

The paper presents a decomposition of income mobility indices into two basic sources: mobility induced by a change of the income distribution shape, and mobility induced by a reordering of individuals in the income pecking order. The decomposition procedure, based on counterfactual distributions, results in a decomposition that is applicable to a broad class of mobility measures. Application to income ‘movement’ indices with data for Belgium, Western Germany and the USA indicates that reranking has been the major force behind income mobility.
Income Distribution, Non‐convexities and the Fertility–Income Relationship
Authors: Docquier Frédéric
Published: May 2004

This paper presents a model of inequality, income determination and fertility, that is consistent with aggregated stylized facts and individual survey data on fertility and income. It shows that indivisibilities in human capital investments limit the possibility of trade‐off between the quality and the quantity of children. This generates a non‐monotonic relationship between income and fertility at the micro level. On the aggregate, the total fertility rate can increase or decrease with income, depending on the income distribution of the population and on the private cost of education.
The Business Cycle, Macroeconomic Shocks and the Cross‐Section: The Growth of UK Quoted Companies
Authors: Higson C. , Holly S. , Kattuman P. , Platis S.
Published: May 2004

We bring to light a significant aspect of firm level heterogeneity over the business cycle. Analysing the responsiveness of firm growth (quoted UK companies) to aggregate shocks, we find that the effects of aggregate shocks are more pronounced for firms in the middle range of growth. Rapidly growing and rapidly declining firms are less sensitive to aggregate shocks than firms in the interior of the growth range. This is consistent with the fact that the higher moments of the distribution of firm growth rates have significant cyclical patterns. These findings throw new light on growth of firms as well as on business cycle dynamics.
Smooth Extremal Models in Finance and Insurance
Authors: Chavez‐Demoulin V. , Embrechts P.
Published: May 2004

Abstract

This article describes smooth nonstationary generalized additive modeling for sample extremes, in which spline smoothers are incorporated into models for exceedances over high thresholds. We summarize the smoothing methodology as a new tool for practical extreme value exploration in finance and insurance.
Martingale Approach for Moments of Discounted Aggregate Claims
Authors: Jang Ji‐Wook
Published: May 2004

Abstract

We examine the Laplace transform of the distribution of the shot noise process using the martingale. Applying the piecewise deterministic Markov processes theory and using the relationship between the shot noise process and the accumulated/discounted aggregate claims process, the Laplace transform of the distribution of the accumulated aggregate claims is obtained. Assuming that the claim arrival process follows the Poisson process and claim sizes are assumed to be exponential and mixture of exponential, we derive the explicit expressions of the actuarial net premiums and variances of the discounted aggregate claims, which are the annuities paid continuously. Numerical examples are also provided based on them.
Incentives for Managing Accounting Information: Property‐Liability Insurer Stock‐Charter Conversions
Authors: Mayers David , Smith Clifford W.
Published: May 2004

Abstract

Incentives to manage accounting information are examined within 63 property‐liability insurance company conversions from mutual ownership to common stock charter. In the conversion process, policyholders' embedded equity claims must be valued. Since mutuals have no separately traded equity, accounting numbers are a critical input in this valuation. Incentives for surplus management vary across firms; the strongest evidence of surplus management is observed among firms where the mutual's executives become the firm's principal stockholders following conversion. The evidence suggests that converting firms manage accounting information primarily by adjusting liabilities and selectively establishing investment losses—not by altering claims settlement policy.
Law and the Determinants of Property‐Casualty Insurance
Authors: Esho Neil , Kirievsky Anatoly , Ward Damian , Zurbruegg Ralf
Published: May 2004

Abstract

This article examines the importance of legal rights and enforcement in influencing property‐casualty insurance (PCI) consumption. We extend the existing literature by examining the role of legal factors in determining insurance density across countries. Also, measures of risk aversion, loss probability, and price, which overcome limitations of proxies used in the existing literature on insurance demand, are analyzed. Using a panel data set, we apply a generalized methods of moments dynamic system estimator, which relaxes the assumption of strict exogeneity of the regressors and produces unbiased and efficient estimates. The results show a strong positive relationship between the protection of property rights and insurance consumption, which is robust to various model specifications and estimation techniques. Moreover, the results show the purchase of PCI is significantly and positively related to loss probability and income, as well as providing weaker evidence of a negative relationship with price.
Dendritic Cell Vaccine Therapy by Immunization with Fusion Cells of Interleukin‐2 Gene‐Transduced, Spleen‐Derived Dendritic Cells and Tumour Cells
Authors: Ogawa F. , Iinuma H. , Okinaga K.
Published: May 2004

We examined the preventive and therapeutic effects of fusion cells prepared from spleen‐derived dendritic cells (DCs) transduced with the interleukin‐2 (IL‐2) gene and QRsP fibrosarcoma cells in a mouse lung metastasis model. The IL‐2 or LacZ gene was introduced into spleen‐derived DCs using an adenoviral vector. Irradiated QRsP tumour cells were fused with IL‐2 gene‐transduced DCs (fusion/IL‐2) or LacZ gene‐transduced DCs (fusion/LacZ) by polyethylene glycol. These fusion cells expressed major histocompatibility complexes (MHC) class I and II, CD86, CD11c and CD8α. Splenocytes from mice vaccinated with fusion cells showed increased production of interferon‐γ (IFN‐γ) and cytotoxic T‐lymphocyte (CTL) activity as compared with those vaccinated with DCs or tumour cells alone, and CTL levels were higher in fusion/IL‐2‐vaccinated mice than in fusion/LacZ‐vaccinated mice. In our experiments on the protective and therapeutic effects on lung metastasis, mice vaccinated with fusion/IL‐2 fusion/LacZ or fusion showed a significant reduction in pulmonary metastasis compared with those given DCs, tumour or phosphate‐buffered saline. The introduction of the IL‐2 gene into fusion cells produced more potent preventive and therapeutic effects. These results suggest that immunization with fusion cells prepared from spleen‐derived DCs and tumour cells is capable of inducing preventive and therapeutic anti‐tumour immunity against lung metastasis, and modification by the IL‐2 gene may increase anti‐tumour efficacy.
Modulation of Adhesion Molecule Expression on Endothelial Cells after Induction by Lipopolysaccharide‐Stimulated Whole Blood
Authors: Nooteboom A. , Van Der Linden C. J. , Hendriks T.
Published: May 2004

The relative contribution of the pro‐inflammatory cytokines tumour necrosis factor (TNF)‐α and interleukin (IL)‐1β and the lipopolysaccharide (LPS)‐induced pathways that result in endothelial activation during sepsis are not fully understood. We have examined the effects of plasma obtained from LPS‐treated human whole blood on the expression of E‐selectin and intercellular adhesion molecule‐1 (ICAM‐1) on human endothelial cells. Stimulation of blood with 10 pg/ml of LPS is sufficient to produce plasma that induces E‐selectin and ICAM‐1 expression, while direct induction by LPS alone requires a 100‐fold higher concentration. Characteristics for the plasma‐induced adhesion molecule expression were similar to the LPS‐induced production of TNF‐α and IL‐1β in blood. A complete inhibition of E‐selectin and ICAM‐1 expression was observed when antibodies against TNF‐α and IL‐1β were added to plasma prior to the incubation to endothelial cultures. Significant inhibition was even observed if antibodies were added to the cultures up until 3 h after LPS‐conditioned plasma. The plasma‐induced adhesion molecule response could also be prevented with inhibitors of nuclear factor (NF)‐κB, such as pyrollidine dithiocarbamate. These findings emphasize the central role of TNF‐α and IL‐1β in LPS‐induced endothelial activation and suggest that simultaneous neutralization of these cytokines or their common pathways may, even after the initial stimulus, prevent endothelial response during sepsis.
Delaying Acute Graft‐Versus‐Host Disease in Mouse Bone Marrow Transplantation by Treating Donor Cells with Antibodies Directed at l‐Selectin and α4‐Integrin Prior to Infusion
Authors: Li B. , New J. Y. , Tay Y. K. , Goh E. , Yap E. H. , Chan S. H. , Hu H. Z.
Published: May 2004

Acute graft‐versus‐host disease (GVHD) is still a major hurdle for successful bone marrow transplantation (BMT). Although many immunosuppressive drugs are available, none of them alone or in combination are able to completely abolish acute GVHD. The lifelong immunosuppression profoundly reduces the quality of life of BMT recipients. Therefore, new therapeutic approaches are needed. We previously reported that, in an acute GVHD model using SCID mice as recipient, incubating donor spleen cells with antibodies directed at CD49d and CD62L could significantly delay the occurrence of acute GVHD. To test the potential usefulness of this treatment in BMT, we examined this therapeutic protocol in a mouse BMT model. The present mouse BMT study confirmed our previous results that incubation of donor cells with antibodies directed at CD49d and CD62L prior to infusion into the recipient can effectively delay acute GVHD, allowing the recipients to recover from the side effects of total body irradiation. This one‐time treatment is easy and simple and may be modified for clinical usage.
Mercuric Chloride Induces a Strong Immune Activation, but does not Accelerate the Development of Dermal Fibrosis in Tight Skin 1 Mice
Authors: Hansson M. , Abedi‐Valugerdi M.
Published: May 2004

In susceptible mice, mercuric chloride induces a systemic autoimmune disease characterized by increased serum levels of immunoglobulin (Ig) G1 and IgE, production of anti‐nucleolar autoantibodies (ANolA) and formation of renal IgG deposits. We have previously hypothesized that mercury confers more adverse immunological effects on those mouse strains, which are genetically prone to develop spontaneous autoimmune diseases than on normal strains. In this study, we tested our hypothesis in tight skin 1 (Tsk1/+) mice, a murine model for human scleroderma. As a support for our hypothesis, we observed that in Tsk1/+ mice, B cells were spontaneously hyperactive and that treatment with mercury induced a strong immune/autoimmune response in these mice, but not in their non‐Tsk (+/+) littermates. This response was characterized by the formation of high numbers of splenic IgG1, IgG2b and IgG3 antibody‐secreting cells, increased serum levels of IgE, production of IgG1 antibodies against single‐stranded DNA (ssDNA), trinitrophenol (TNP) as well as thyroglobulin and the development of renal IgG1 deposits. Neither Tsk1/+ mice nor F1 hybrid crosses between this strain, and mercury susceptible B10.S (H‐2s) were able to produce IgG1‐ANolA in response to mercury. Moreover, mercury‐induced immune activation in Tsk1/+ was not able to potentiate the progression of skin fibrosis in this strain. Thus, exposure to mercury accelerates the immune dysregulation, but not the development of skin fibrosis in Tsk1/+ mice.
Effect of Different Cell Fractions of Mycobacterium avium and Vaccination Regimens on Mycobacterium avium Infection
Authors: Falkinham J. O. , Gross W. B. , Pierson F. W.
Published: May 2004

Because of the availability of uniform genetic stocks and the ability to modulate stress levels, chickens were investigated as a host for the development of an antimycobacterial vaccine. The imposition and the timing of stress significantly influenced the outcome of Mycobacterium avium infection in chickens. Simple, whole cell or lysate vaccines and combinations of vaccine preparations were identified that led to high levels of protection. In addition, short‐term stress at the time of vaccination significantly increased the protective efficacy of M. avium vaccine preparations. Post‐infection vaccination of M. avium‐infected chickens was also shown to significantly reduce the number of lesions and colony counts.
Cytokine Profile in Children During the First 3 Months after the Diagnosis of Type 1 Diabetes
Authors: Karlsson Faresjö M. G. E. , Ernerudh J. , Ludvigsson J.
Published: May 2004

Type 1 diabetes is an autoimmune disease with an inflammatory process directed against the β cells in pancreas. This investigation aimed at studying the immune response during the first 3 months after the diagnosis of type 1 diabetes, with focus on the balance of T‐helper 1 (Th1)‐ and Th2‐like cytokines, produced spontaneously and in response to relevant autoantigens. Peripheral blood mononuclear cells (PBMCs) were collected from type 1 diabetic children (10–17 years) at 5, 20, 35 and 90 days after diagnosis. Expression of interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) mRNA were detected by real‐time reverse transcriptase polymerase chain reaction and IFN‐γ, IL‐10 and IL‐13 by enzyme‐linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD65)‐peptide [amino acid (a.a.) 247–279], insulin, the ABBOS‐peptide (a.a. 152–169), phytohaemagglutinin and keyhole limpet haemocyanin. Spontaneous and antigen‐induced expression and secretion of cytokines were low at the diagnosis of type 1 diabetes. During the first month, after diagnosis, the GAD65‐peptide caused an increased ratio of IFN‐γ/IL‐4 mRNA expression (P < 0.05) and increased secretion of IFN‐γ (P = 0.07). Expression of IFN‐γ mRNA did also increase from stimulation with insulin (P < 0.05), even though cytokine secretion remained low. Thus, duration after diagnosis as well as metabolic state should be carefully considered both in studies of the pathogenesis of type 1 diabetes and in immune intervention studies at onset.
Tumour Necrosis Factor Receptor Superfamily Member 6 Gene Mutation Detection by Denaturing High‐Performance Liquid Chromatography
Authors: Etokebe G. E. , Abrahamsen T. G. , Bogen B. , Spurkland A.
Published: May 2004

Denaturing high‐performance liquid chromatography (DHPLC) was evaluated as a tool for diagnostic screening of polymorphisms in the tumour necrosis factor receptor superfamily member 6 (TNFRSF6) also known as CD95, Apo‐1 or Fas gene. Exons 1–9 of the TNFRSF6 gene were amplified from genomic DNA of 38 individuals, of which three were known to carry mutations in the TNFRSF6 gene. The TNFRSF6 gene amplicons were analysed for heterozygosity by DHPLC. Samples that displayed heterozygous variation by DHPLC were further analysed by sequencing. Comparison of DHPLC analysis with sequencing results showed an overall 100% concordance for samples in which heterozygosity was detected by DHPLC. Importantly, DHPLC was in all cases able to demonstrate the presence or absence of mutations in exon 9 encoding the death domain of the TNFRSF6 gene, which have been implied as the most frequent genetic cause of autoimmune lymphoproliferative syndrome. Comparison of DHPLC analysis with sequencing results showed an overall 100% concordance for samples in which heterozygosity was detected by DHPLC. In conclusion, DHPLC is a suitable method for the detection of genetic variation in the TNFRSF6 gene.
Interaction of C1q with the Receptor Calreticulin Requires a Conformational Change in C1q
Authors: Steinø A. , Jørgensen C. S. , Laursen I. , Houen G.
Published: May 2004

The interaction between C1q and the chaperone calreticulin was studied under various conditions. When both proteins were present in equal amounts in solution, no interaction could be demonstrated. However, C1q immobilized on a hydrophobic surface, exposed to heat‐treatment or bound to immunoglobulins (Igs) showed a strong, rapid and specific binding of calreticulin. The interaction appeared to be a two‐step process, and the initial phase of interaction was sensitive to high concentrations of salt but not to a physiological salt concentration. The following strong binding was insensitive to salt and extremes of pH but sensitive to strongly denaturing agents (urea and guanidine). The sensitivity to salt during the initial phase of interaction was practically identical to that observed when calreticulin was bound to type V collagen. Binding between C1q and calreticulin could be inhibited by serum amyloid P component and by proteinase K‐digested ovalbumin, and the binding of calreticulin to proteinase K‐digested ovalbumin was shown to be inhibited by C1q. The data indicate that C1q binds stably to the peptide‐binding site of calreticulin and that the initial binding of calreticulin to C1q involves the collagen‐like domain of the C1q molecule. In conclusion, our results suggest calreticulin as a potential receptor for an altered conformation of C1q as occurs during binding to Igs. Thus, the chaperone and protein‐scavenging function of calreticulin may extend from the endoplasmic reticulum to the topologically equivalent cell surface, where it may contribute to the elimination of immune complexes and apoptotic cells.
DC‐SIGN‐Specific Liposomal Targeting and Selective Intracellular Compound Delivery to Human Myeloid Dendritic Cells: Implications for HIV Disease
Authors: Gieseler R. K. , Marquitan G. , Hahn M. J. , Perdon L. A. , Driessen W. H. P. , Sullivan S. M. , Scolaro M. J.
Published: May 2004

Myeloid dendritic cells (MyDCs), prime stimulators of antigen‐specific immunity, can serve as one of the major reservoirs for human immunodeficiency virus type‐1 (HIV‐1). Utilizing mature monocyte‐derived MyDCs generated with granulocyte/macrophage colony‐stimulating factor, interleukin‐4, and tumour necrosis factor‐α as an in vitro model, we here present the first proof of concept for liposomal compound delivery to these cells by specifically addressing CD209, i.e. DC‐specific intercellular adhesion molecule 3‐grabbing nonintegrin (DC‐SIGN), a MyDC‐associated C‐type lectin implicated in the transmission of HIV‐1 to T helper cells. By employing a liposomally entrapped tracer, calcein, we demonstrate by flow cytometry and mathematics a superior targeting efficacy for DC‐SIGN, as compared with select other MyDC markers (CD1a, CD4, CD45R0, and CD83). Fluorescence microscopy reveals time‐dependent surface binding and intracellular uptake of DC‐SIGN‐specific liposomes by both immature and mature MyDCs. This pilot study implies that liposomal targeting to CD209 and related C‐type lectins may afford therapeutic intracellular drug delivery to MyDCs and other reservoir and nonreservoir cells susceptible to infection with HIV‐1.
A new test for immunological infertility: an ELISA based on prostasomes
Authors: Carlsson L. , Nilsson B. O. , Ronquist G. , Lundquist M. , Larsson A.
Published: May 2004

Antisperm antibodies (ASA) are present in patients with immunological infertility, but the antigens are poorly characterized. Prostasomes adhere to sperm cells and are recognized as antigens for ASA. This investigation aimed to study the prevalence of antiprostasome antibodies in ASA‐classified sera. We studied the reactivity of ASA‐positive sera from 116 immunoinfertile patients. Ninety‐seven per cent (113 of 116) of the patients’ sera contained IgG antibodies against seminal prostasomes. Accordingly, prostasomes are one of the major targets for ASA. An enzyme‐linked immunosorbent assay based on prostasomes is simpler to perform than ASA tests presently in use. It is also easier to achieve reproducible and standardized results.
Outpatient penile implantation with the patient under a novel method of crural block
Authors: Hsu Geng‐Long , Hsieh Cheng‐Hsing , Wen Hsien‐Sheng , Chen Shyh‐Chyan , Chen Yi‐Chang , Liu Li‐Jen , Mok Martin S. , Wu Chih‐Hsiung
Published: May 2004

Although local anaesthesia for penile implants has been substantially reported, its methodology, simplicity and reliability left room for improvement. We would like to report on an innovative penile crural block using local anaesthesia in patients who underwent penile implantation as outpatient surgery. From March 1987 to March 1991, a total of 21 organically impotent men, aged from 27 to 77 years, received penile prosthesis implantation. All these were performed under pudendal nerve block as an outpatient procedure. From August 1992 to January 2003 a proximal dorsal nerve block with peripenile infiltration and penile crural block was developed to replace the anaesthesia method of pudendal nerve blocks in 137 consecutive patients (aged from 35 to 83 years) undergoing penile implants. The anaesthetic effects and postoperative results with the crural block were very satisfactory. Common immediate side‐effects included puncture of the vessels, subcutaneous ecchymosis, transient palpitations and dilation pain, but there were no significant late complications. In the group of pudendal nerve blockage, 42.9% patients (nine of 21) experienced severe aching pain over the perineum for 1–2 weeks postoperatively, whereas the newly developed method of crural block markedly reduced these adverse effects. This new anaesthetic method proved to be reliable, simple, and safe with fewer complications. It offers the advantages of less morbidity, preservation of patient's privacy, reduced adverse effects of anaesthesia, and a more‐rapid return to activity with minimal complications.
Variations in quality of frozen–thawed semen from Swedish Red and White AI sires at 1 and 4 years of age
Authors: Hallap Triin , Håård Margareta , Jaakma Ülle , Larsson Birgitta , Rodriguez‐Martinez Heriberto
Published: May 2004

The predictability of semen quality of mature sires from measurements at an early age is not well established. The aim of the present study was to determine age‐dependent changes in the quality of bull semen for artificial insemination (AI). Semen was collected and frozen from each of six Swedish Red and White (SRB) dairy AI bulls when they were 1 and 4 years old. Three batches were randomly selected from each bull and age group. From each batch, semen was analysed immediately after thawing [post‐thaw (PT), control] as well as after washing/resuspension (W) and after a swim‐up procedure (SU). The analyses comprised subjective and computerized (computer‐aided sperm analysis, CASA) measurements of motility as well as sperm concentration, morphology and membrane integrity. When semen was analysed, PT, overall sperm motility (CASA), concentration of motile spermatozoa and membrane integrity improved when sires were older. After SU, there was a similar improvement in membrane integrity and concentration of motile spermatozoa, but linear motility decreased. No significant differences between ages were recorded after W‐treatment. The above findings indicate that SU is not only superior to W‐treatment in differentiating semen quality among bulls but also reveals age‐dependent changes. Improved motility and membrane integrity suggest increased viability of spermatozoa at 4 years of age in the SRB sires examined here.
Ketone bodies could support the motility but not the acrosome reaction of mouse sperm
Authors: Tanaka Hiromitsu , Takahashi Tohru , Iguchi Naoko , Kitamura Kouichi , Miyagawa Yasushi , Tsujimura Akira , Matsumiya Kiyomi , Okuyama Akihiko , Nishimune Yoshitake
Published: May 2004

Ketone bodies, D‐β‐hydroxybutyrate and acetoacetate, produced by the metabolism of fatty acids, are an important energy source for many organs, especially the heart, kidney and brain. They are utilized by the body with the help of succinyl CoA transferase (SCOT), which is ubiquitously expressed in various organs. Previously, we identified a novel SCOT‐t specifically expressed in testicular germ cells and sperm, substituting somatic cell‐type SCOT, however the physiological role of SCOT‐t had not then been clarified. In the present study, we investigated the effects of ketone bodies, the substrate of SCOT‐t, on the motility and acrosome reaction of mouse sperm. D‐β‐hydroxybutyrate and acetoacetate both stimulated the motility of sperm as glucose or pyruvate. The glycolysis inhibitor stopped the motility of sperm mediated by glucose but not by D‐β‐hydroxybutyrate. In contrast, ketone bodies did not stimulate the activation of the acrosome reaction of sperm, different from the effect of glucose. These results indicate that ketone bodies could be involved in sperm movement but not the acrosome reaction and the SCOT‐t enzyme we have identified in sperm mitochondria may have important roles in the activity of sperm, resulting in male infertility when its function is disabled.
Increased nitric oxide is accompanied by lipid oxidation in adolescent varicocele
Authors: Türkyilmaz Zafer , Gülen Şebnem , Sönmez Kaan , Karabulut Ramazan , Dinçer Sibel , Can Başaklar A. , Kale Nuri
Published: May 2004

One of the mechanisms of injury in varicocele has been proposed to be elevated nitric oxide (NO). We aimed to determine the association between the elevation of NO and lipid oxidation in varicocele compared with peripheral venous levels of these two substances as it has not been studied before. The study group consisted of 13 adolescents with left idiopathic varicocele of grades II–III. Blood specimens were obtained from dilated spermatic and peripheral veins simultaneously. Peripheral samples were also collected from 13 healthy children as controls. Nitrite/nitrate levels (NOx) and levels of malonedialdehyde (MDA) were determined using Griess reaction and thiobarbituric acid test, respectively. Results were compared with Kruskal–Wallis and Mann–Whitney tests. Peripheral NOx and MDA were the same in the study and control groups (p = 0.069 and p = 0.27, respectively). Spermatic vein NOx and MDA levels were elevated significantly compared with the peripheral levels in the study group (p = 0.005 and p = 0.048, respectively). Increased NOx levels with lipid oxidation occur locally in adolescent varicocele, implying that these events could be reversed by early treatment.
Is an expanded nurse role economically viable?
Authors: Lee Taewha , Ko Il‐Sun , Jeong Seok Hee
Published: May 2004

Rationale. Community health practitioners (CHPs) in Korea are Registered Nurses with a 6‐month special training who have responsibility for delivering primary health care to remote or isolated communities. Research has indicated that these practitioners’ contribution to improving the health of rural and remote populations has been effective. Despite this, CHP programmes have been fundamentally re‐examined by the Korean government, as a consequence of the national economic crisis of 1998 and restructuring of the health care delivery system.

Aim. The aim of this paper is to analyse CHP services in primary health care, and evaluate some of the economic impacts of these services through a cost‐minimization analysis.

Methods. A retrospective, descriptive‐correlational design was used. A self‐administered questionnaire was sent to 600 CHPs who were randomly selected from the target population, and 272 returned the questionnaire after one reminder letter, a response rate of 45·3%.

Results. There was a significant difference in average cost of care between a model based on CHP services and one including no CHP services, in which equivalent care was provided by physicians (t = −6·833, P < 0·001). The average costs ratio was 2·16 (sd = 1·24), with a range of 0·09–9·63, indicating that CHP services were almost half the price of the ‘no CHP services’ model.

Conclusions. The results provide evidence of the economic validity of the CHP's role in the public sector, where there is no net income to serve as a policy guideline. The conclusion can be drawn that CHP services are more effective than physician services (or ‘no CHP services’).