bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of interferon‐alpha administration after 2‐deoxycoformycin in the treatment of hairy cell leukemia patients
Authors: Marotta Giuseppe , Frassoldati Antonio , Zinzani Pierluigi , Annino Luciana , Brugiatelli Maura , Ambrosetti Achille , Lenoci Mariapia , Federico Massimo , Foa Robin , Lauria Francesco ,   the Italian Cooperative group for HCL (ICGHCL)
Published: April 2006

Abstract:  Background and objective: Hairy cell leukemia (HCL) is a rare chronic B‐cell lymphoproliferative disorder which is treated effectively by interferon‐alpha (IFN‐α), deoxycoformycin (DCF) and 2‐clorodeoxyadenosine (2‐CdA). As a third of patients treated with DCF do not achieve a complete remission (CR) and many of them tend to relapse, we evaluated the potential role of IFN‐α, randomly administered after DCF, in increasing the number of patients attaining CR and/or duration of CR. Methods: From March 1997 to December 2000, 167 previously untreated HCL patients, from 37 Italian institutions, were enrolled in the study. A total of 138 males and 29 females, with a median age of 55 yr were included in the study. All patients received six courses of DCF 4 mg/m2 i.v. every other week and then two additional courses once a month. Complete and partial responders were randomly assigned to receive or not receive IFN‐α at a dose of 3 MU s.c. three times a week for 6 months. Results: Of the 167 patients enrolled in the study, 145 (86.8%) obtained a CR or a partial remission (PR) and were therefore suitable for randomization. One hundred and thirty‐five patients were successively randomized to receive IFN‐α (63 cases; arm A) or not (72 cases; arm B). Progression of disease was observed in eight (arm A) and 12 (arm B) patients with a median time of 27.8 and 26.9 months, respectively. As far as the improvement in response was concerned, no significant difference in the two subgroups was observed. In fact, five patients in arm A and six patients in arm B showing a good PR at the end of DCF therapy, subsequently attained a late CR. Conclusions: From our data there does not appear to be any significant role for IFN‐α in improving the proportion and the duration of CR in HCL patients previously treated with DCF.
Financial Spread Betting
Authors: Buik David
Published: April 2006

Traditional betting has two outcomes: you win or you lose. Spread betting has many more possibilities: you can win a lot or a little; you can lose or lose much, much more than you imagined. Spread betting, say its fans, brings a whole new level of uncertainty—and excitement. It has been described as the crack cocaine of gambling. Spread bets can be laid on almost any sporting or other result, but in the field of finance it is making particular inroads. David Buik, of the City spread betting company Cantor Index Ltd, explains.
Dettori Day
Authors: Docherty Jenny
Published: April 2006

It was the day at the races the bookies want to forget. September 28th, 1996, was the one day that dreams came true for punters—they made a killing and, for once, went home richer than the bookmakers. It was the day that Frankie Dettori rode all seven winners at Ascot. Jenny Docherty describes the day's events.
Transcriptome Analysis Reveals Mechanisms by Which
Lactococcus lactis
Acquires Nisin Resistance
Authors: Kramer Naomi E. , van Hijum Sacha A. F. T. , Knol Jan , Kok Jan , Kuipers Oscar P.
Published: April 2006

Nisin, a posttranslationally modified antimicrobial peptide produced by
Lactococcus lactis
, is widely used as a food preservative. Yet, the mechanisms leading to the development of nisin resistance in bacteria are poorly understood. We used whole-genome DNA microarrays of
L. lactis
IL1403 to identify the factors underlying acquired nisin resistance mechanisms. The transcriptomes of
L. lactis
IL1403 and
L. lactis
IL1403 Nis
r
, which reached a 75-fold higher nisin resistance level, were compared. Differential expression was observed in genes encoding proteins that are involved in cell wall biosynthesis, energy metabolism, fatty acid and phospholipid metabolism, regulatory functions, and metal and/or peptide transport and binding. These results were further substantiated by showing that several knockout and overexpression mutants of these genes had strongly altered nisin resistance levels and that some knockout strains could no longer become resistant to the same level of nisin as that of the wild-type strain. The acquired nisin resistance mechanism in
L. lactis
is complex, involving various different mechanisms. The four major mechanisms are (i) preventing nisin from reaching the cytoplasmic membrane, (ii) reducing the acidity of the extracellular medium, thereby stimulating the binding of nisin to the cell wall, (iii) preventing the insertion of nisin into the membrane, and (iv) possibly transporting nisin across the membrane or extruding nisin out of the membrane.
Minocycline Impedes African Trypanosome Invasion of the Brain in a Murine Model
Authors: Masocha Willias , Rottenberg Martin E. , Kristensson Krister
Published: April 2006

Passage of
Trypanosoma brucei
across the blood-brain barrier (BBB) is a hallmark of late-stage human African trypanosomiasis. In the present study we found that daily administration of minocycline, a tetracycline antibiotic, impedes the penetration of leukocytes and trypanosomes into the brain parenchyma of
T. brucei brucei
-infected C57BL/6 mice. The trypanosome-induced astrocytic and microglial reactions were reduced in the minocycline-treated mice, as were the levels in the brain of transcripts encoding adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and endothelial-leukocyte adhesion molecule 1 (E-selectin); the inflammatory cytokines tumor necrosis factor alpha, interleukin-1α (IL-1α), IL-1β, IL-6, and gamma interferon; and matrix metalloprotease 3 (MMP-3), MMP-8, and MMP-12. Loss of weight occurring during infection with
T. b. brucei
was not observed after treatment of the mice with minocycline; these mice also survived longer than nontreated mice. Invasion of trypanosomes and leukocytes into the brain parenchyma most likely triggered the loss of weight and death of infected animals, since minocycline did not affect the growth of
T. b. brucei
either in vitro or in vivo or the levels of the transcripts encoding the cytokines and MMPs in the spleen. In conclusion, our data show that
T. b. brucei
invasion of the brain is related to that of leukocytes and that minocycline can ameliorate the disease in trypanosome-infected mice.
VX-950, a Novel Hepatitis C Virus (HCV) NS3-4A Protease Inhibitor, Exhibits Potent Antiviral Activities in HCV Replicon Cells
Authors: Lin Kai , Perni Robert B. , Kwong Ann D. , Lin Chao
Published: April 2006

The NS3-4A serine protease of hepatitis C virus (HCV) is essential for viral replication and therefore has been one of the most attractive targets for developing specific antiviral agents against HCV. VX-950, a highly selective, reversible, and potent peptidomimetic inhibitor of the HCV NS3-4A protease, is currently in clinical development for the treatment of hepatitis C. In this report, we describe the in vitro characterization of anti-HCV activities of VX-950 in subgenomic HCV replicon cells. Incubation with VX-950 resulted in a time- and dose-dependent reduction of HCV RNA and proteins in replicon cells. Moreover, following a 2-week incubation with VX-950, a reduction in HCV RNA levels of 4.7 log
10
was observed, and this reduction resulted in elimination of HCV RNA from replicon cells, since there was no rebound in replicon RNA after withdrawal of the inhibitor. The combination of VX-950 and alpha interferon was additive to moderately synergistic in reducing HCV RNA in replicon cells with no significant increase in cytotoxicity. The benefit of the combination was sustained over time: a 4-log
10
reduction in HCV RNA level was achieved following a 9-day incubation with VX-950 and alpha interferon at lower concentrations than when either VX-950 or alpha interferon was used alone. The combination of VX-950 and alpha interferon also suppressed the emergence of in vitro resistance mutations against VX-950 in replicon cells.
Nebulized Amphotericin B Combined with Intravenous Amphotericin B in Rats with Severe Invasive Pulmonary Aspergillosis
Authors: Ruijgrok Elisabeth J. , Fens Marcel H. A. M. , Bakker-Woudenberg Irma A. J. M. , van Etten Els W. M. , Vulto Arnold G.
Published: April 2006

Nebulized amphotericin B (AMB) combined with intravenous AMB was studied in persistently leukopenic rats with invasive pulmonary aspergillosis. Pulmonary concentrations of AMB after aerosol treatment were substantially higher than after intravenous liposomal AMB. Nebulized liposomal AMB in addition to intravenous AMB resulted in significantly prolonged survival compared to controls.
Vibrio cholerae
InV117, a Class 1 Integron Harboring
aac(6′)-Ib
and
bla
CTX-M-2
, Is Linked to Transposition Genes
Authors: Soler Bistué Alfonso J. C. , Martín Fernando A. , Petroni Alejandro , Faccone Diego , Galas Marcelo , Tolmasky Marcelo E. , Zorreguieta Angeles
Published: April 2006

A ca. 150-kbp
Vibrio cholerae
O1 biotype El Tor plasmid includes
bla
CTX-M-2
and a variant of
aac(6′)-Ib
within InV117, an orf513-bearing class 1 integron. InV117 is linked to a
tnp1696
module in which IRl carries an insertion of IS
4321
R. The complete structure could be a potential mobile element.
Virucidal Activity of a GT-Rich Oligonucleotide against Herpes Simplex Virus Mediated by Glycoprotein B
Authors: Shogan Benjamin , Kruse Lori , Mulamba Gilbert B. , Hu André , Coen Donald M.
Published: April 2006

We have investigated the antiviral mechanism of a phosphorothioate oligonucleotide, ISIS 5652, which has activity against herpes simplex virus (HSV) in the low micromolar range in plaque reduction assays. We isolated a mutant that is resistant to this compound. Marker rescue and sequencing experiments showed that resistance was due to at least one of three mutations in the
UL27
gene which result in amino acid changes in glycoprotein B (gB). Because gB has a role in attachment and entry of HSV, we tested the effects of ISIS 5652 at these stages of infection. The oligonucleotide potently inhibited attachment of virus to cells at 4°C; however, the resistant mutant did not exhibit resistance at this stage. Moreover, a different oligonucleotide with little activity in plaque reduction assays was as potent as ISIS 5652 in inhibiting attachment. Similarly, ISIS 5652 was able to inhibit entry of preattached virions into cells at 37°C, but the mutant did not exhibit resistance in this assay. The mutant did not attach to or enter cells more quickly than did wild-type virus. Strikingly, incubation of wild-type virus with 1 to 2 μM ISIS 5652 at 37°C led to a time-dependent, irreversible loss of infectivity (virucidal activity). No virucidal activity was detected at 4°C or with an unrelated oligonucleotide at 37°C. The resistant mutant and a marker-rescued derivative containing its
gB
mutations exhibited substantial resistance to this virucidal activity of ISIS 5652. We hypothesize that the GT-rich oligonucleotide induces a conformational change in gB that results in inactivation of infectivity.
Effects of an Opal Termination Codon Preceding the nsP4 Gene Sequence in the O'Nyong-Nyong Virus Genome on
Anopheles gambiae
Infectivity
Authors: Myles Kevin M. , Kelly Cindy L. H. , Ledermann Jeremy P. , Powers Ann M.
Published: April 2006

The genomic RNA of an alphavirus encodes four different nonstructural proteins, nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation terminates at an opal termination codon between nsP3 and nsP4. The polyprotein P1234 is produced when translational readthrough occurs or when the opal termination codon has been replaced by a sense codon in the alphavirus genome. Evolutionary pressures appear to have maintained genomic sequences encoding both a stop codon (opal) and an open reading frame (arginine) as a general feature of the O'nyong-nyong virus (ONNV) genome, indicating that both are required at some point. Alternate replication of ONNVs in both vertebrate and invertebrate hosts may determine predominance of a particular codon at this locus in the viral quasispecies. However, no systematic study has previously tested this hypothesis in whole animals. We report here the results of the first study to investigate in a natural mosquito host the functional significance of the opal stop codon in an alphavirus genome. We used a full-length cDNA clone of ONNV to construct a series of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal, ochre, or amber stop codon. The presence of an opal stop codon upstream of nsP4 nearly doubled (75.5%) the infectivity of ONNV over that of virus possessing a codon for the amino acid arginine at the corresponding position (39.8%). Although the frequency with which the opal virus disseminated from the mosquito midgut did not differ significantly from that of the arginine virus on days 8 and 10, dissemination did began earlier in mosquitoes infected with the opal virus. Although a clear fitness advantage is provided to ONNV by the presence of an opal codon between nsP3 and nsP4 in
Anopheles gambiae
, sequence analysis of ONNV RNA extracted from mosquito bodies and heads indicated codon usage at this position corresponded with that of the virus administered in the blood meal. These results suggest that while selection of ONNV variants is occurring, de novo mutation at the position between nsP3 and nsP4 does not readily occur in the mosquito. Taken together, these results suggest that the primary fitness advantage provided to ONNV by the presence of an opal codon between nsP3 and nsP4 is related to mosquito infectivity.
EXPECTED COALESCENCE RATES OF NS-NS BINARIES FOR LASER BEAM INTERFEROMETERS
Authors: DE FREITAS PACHECO J. A. , REGIMBAU T. , VINCENT S. , SPALLICCI A.
Published: April 2006

The coalescence rate of two neutron stars (NS) is revisited. To estimate the number of bound NS-NS and the probability of their coalescence in a time scale τ, the galactic star formation history, directly derived from observations, and the evolution of massive stars are considered. The newly established galactic merging rate is (1.7±1.0) × 10-5 yr -1, while the local merging rate, including the contribution of elliptical galaxies, is about a factor of two higher, 3.4 × 10-5 yr -1. Using the present data basis on galaxy distribution in the local universe and the expected sensitivity of the first generation of laser beam interferometers, we estimate that one event should occur every 125 years for LIGO and one event each 148 years for VIRGO. The situation is considerably improved for advanced-LIGO, since we predict that 6 events per year should be detected whereas for a recently proposed VIRGO new configuration, the event rate might increase up to 3 events every two years.
COMMENTS ON "ON THE SPEED OF GRAVITY AND THE JUPITER/QUASAR MEASUREMENT" BY S. SAMUEL
Authors: KOPEIKIN SERGEI M.
Published: April 2006

A recent review article by S. Samuel "On the Speed of Gravity and the Jupiter/Quasar Measurement" published as Int. J. Mod. Phys. D13, 1753 (2004), provides the reader with a misleading "theory" of the relativistic time delay in the general theory of relativity. Furthermore, it misquotes original publications by Kopeikin and Fomalont and Kopeikin related to the measurement of the speed of gravity by VLBI. We summarize the general relativistic principles of the Lorentz-invariant theory of the propagation of light in a time-dependent gravitational field, derive a Lorentz-invariant expression for the relativistic time delay, and finally explain why Samuel's "theory" is conceptually incorrect and confuses the speed of gravity with the speed of light.
Leucine in food mediates some of the postprandial rise in plasma leptin concentrations
Authors: Lynch Christopher J. , Gern Beth , Lloyd Carolyn , Hutson Susan M. , Eicher Rachel , Vary Thomas C.
Published: April 2006

In vitro, leptin secretion is regulated at the level of mRNA translation by the rapamycin-sensitive mammalian target of rapamycin (mTOR) and its agonist leucine (Leu). Studies were conducted on meal-trained rats to evaluate the potential physiological relevance of these in vitro findings and the role of Leu in affecting rises in plasma leptin observed after a meal. In the first study, we correlated changes in plasma insulin and Leu to mTOR-signaling pathway activation and plasma leptin at different times during meal feeding. Rapid rises in plasma insulin and Leu, along with mTOR signaling (phosphorylation of eIF4G, S6K1, rpS6, and 4E-BP1) in adipose tissue were observed during the 3-h meal and declined thereafter. Plasma leptin rose more slowly, peaking at 3 h, and was inhibited by rapamycin (0.75 mg/kg) pretreatment. In another experiment, oral Leu or norleucine was provided instead of a meal. Leu and norleucine stimulated a rise in plasma leptin; however, the magnitude was less than the response to a complete meal. In a third study, rats were provided a meal that lacked Leu, branched-chain amino acids, or all amino acids. Stimulation of leptin secretion was reduced ∼40% in animals provided the Leu-deficient meal. Further reductions were not observed by removing the other amino acids. Thus Leu appears to regulate most of the effects of dietary amino acids on the postprandial rise in plasma leptin but is responsible only for part of the leptin response to meal feeding.
Acute renal failure: determinants and characteristics of the injury-induced hyperinflammatory response
Authors: Zager Richard A. , Johnson Ali C. M. , Lund Steve , Hanson Sherry
Published: April 2006

Acute renal failure (ARF) markedly sensitizes mice to endotoxin (LPS), as evidenced by exaggerated renal cytokine/chemokine production. This study sought to further characterize this state by testing the following: 1) does anti-inflammatory heme oxygenase-1 (HO-1) upregulation in selected ARF models prevent this response? 2) Is the ARF hyperresponsive state specifically triggered by LPS? 3) Does excess iNOS activity/protein nitrosylation participate in this phenomenon? and 4) are upregulated Toll receptors involved? Mice with either 1) rhabdomyolysis-induced ARF (massive HO-1 overexpression), 2) cisplatin nephrotoxicity, 3) or HO-1 inhibition (Sn protoporphyrin) were challenged with either LPS (a TLR4 ligand), lipoteichoic acid (LTA; a TLR2 ligand), or vehicle. Two hours later, renal and plasma TNF-α/mRNA, MCP-1/mRNA, renal nitrotyrosine/iNOS mRNA, and plasma cytokines were assessed. Renal TLR4 was gauged by mRNA and Western blot analysis. Both ARF models markedly hyperresponded to both LPS and LTA, culminating in exaggerated TNF-α, MCP-1, and iNOS/nitrotryosine increments. This was despite the fact that HO-1 exerted anti-inflammatory effects. TLR4 levels were either normal (cisplatin), or markedly depressed (∼50%; rhabdomyolysis) in the ARF kidneys, despite the LPS hyperresponsive state. 1) The ARF kidney can hyperrespond to chemically dissimilar Toll ligands; 2) HO-1 does not prevent this response; 3) excess NO/protein nitrosylation can result; and 4) this hyperresponsiveness can be expressed with either normal or reduced renal TLR4 expression. This suggests that diverse signaling pathways may be involved.
Functional Unity of the Ponto-Cerebellum: Evidence That Intrapontine Communication Is Mediated by a Reciprocal Loop With the Cerebellar Nuclei
Authors: Möck Martin , Butovas Sergejus , Schwarz Cornelius
Published: April 2006

The majority of cerebral signals destined for the cerebellum are handed over by the pontine nuclei (PN), which thoroughly reorganize the neocortical topography. The PN maps neocortical signals of wide-spread origins into adjacent compartments delineated by spatially precise distribution of cortical terminals and postsynaptic dendrites. We asked whether and how signals interact on the level of the PN. Intracellular fillings of rat PN cells in vitro did not reveal any intrinsic axonal branching neither within the range of the cells' dendrites nor farther away. Furthermore, double whole cell patch recordings did not show any signs of interaction between neighboring pontine cells. Using simultaneous unit recording in the PN and cerebellar nuclei (CN) in rats in vivo, we investigated whether PN compartments interact via extrinsic reciprocal connections with the CN. Repetitive electrical stimulation of the cerebral peduncle of ≤40 Hz readily evoked rapid sequential activation of PN and CN, demonstrating a direct connection between the structures. Stimulation of the PN gray matter led to responses in neurons ≤600 μm away from the stimulation site at latencies compatible with di- or polysynaptic pathways via the CN. Importantly, these interactions were spatially discontinuous around the stimulation electrode suggesting that reciprocal PN-CN loops in addition reflect the compartmentalized organization of the PN. These findings are in line with the idea that the cerebellum makes use of the compartmentalized map in the PN to orchestrate the composition of its own neocortical input.
Measuring Atmospheric Stability with GPS
Authors: de Haan Siebren
Published: April 2006

Nowcasting of convective systems plays a crucial role in weather forecasting. The strength of convection depends on the (in)stability of the air column. The stability can be detected by radiosonde observations. However, these observations are not frequent (typically 2 times per day) and are expensive to deploy. In this article a method is presented to detect the stability of the atmosphere based on high-frequency global positioning system (GPS) path-delay observations. The convection parameter derived from these observations is the power of the nonisotropic GPS path-delay signal. Comparisons with the convective available potential energy obtained from radiosonde observations show a correlation with the convection parameter obtained from GPS. This result implies that, because of the continuous availability of GPS estimates and the good land coverage, this method of detecting atmospheric stability may be beneficial to forecasters.
Decadal Variability of the Midlatitude Climate System Driven by the Ocean Circulation
Authors: Hogg Andrew Mc C. , Dewar William K. , Killworth Peter D. , Blundell Jeffrey R.
Published: April 2006

A midlatitude coupled ocean–atmosphere model is used to investigate interactions between the atmosphere and the wind-driven ocean circulation. This model uses idealized geometry, yet rich and complicated dynamic flow regimes arise in the ocean due to the explicit simulation of geostrophic turbulence. An interdecadal mode of intrinsic ocean variability is found, and this mode projects onto existing atmospheric modes of variability, thereby controlling the time scale of the atmospheric modes. It is also shown that ocean circulation controls the time scale of the SST response to wind forcing, and that coupled feedback mechanisms thus modify variability of the atmospheric circulation. It is concluded that ocean–atmosphere coupling in the midlatitudes is unlikely to produce new modes of variability but may control the temporal behavior of modes that exist in uncoupled systems.
Hepatocyte growth factor mediates angiopoietin-induced smooth muscle cell recruitment
Authors: Kobayashi Hanako , DeBusk Laura M. , Babichev Yael O. , Dumont Daniel J. , Lin Pengnian Charles
Published: April 2006

Communication between endothelial cells (ECs) and mural cells is critical in vascular maturation. Genetic studies suggest that angiopoietin/Tie2 signaling may play a role in the recruitment of pericytes or smooth muscle cells (SMCs) during vascular maturation. However, the molecular mechanism is unclear. We used microarray technology to analyze genes regulated by angiopoietin-1 (Ang1), an agonist ligand for Tie2, in endothelial cells (ECs). We observed that hepatocyte growth factor (HGF), a mediator of mural cell motility, was up-regulated by Ang1 stimulation. We confirmed this finding by Northern blot and Western blot analyses in cultured vascular endothelial cells. Furthermore, stimulation of ECs with Ang1 increased SMC migration toward endothelial cells in a coculture assay. Addition of a neutralizing anti-HGF antibody inhibited Ang1-induced SMC recruitment, indicating that the induction of SMC migration by Ang1 was caused by the increase of HGF. Interestingly, Ang2, an antagonist ligand of Tie2, inhibited Ang1-induced HGF production and Ang1-induced SMC migration. Finally, we showed that deletion of Tie2 in transgenic mouse reduced HGF production. Collectively, our data reveal a novel mechanism of Ang/Tie2 signaling in regulating vascular maturation and suggest that a delicate balance between Ang1 and Ang2 is critical in this process.
Simultaneous bone marrow and intestine transplantation promotes marrow-derived hematopoietic stem cell engraftment and chimerism
Authors: Nakao Atsunori , Toyokawa Hideyoshi , Kimizuka Kei , Nalesnik Michael A. , Nozaki Isao , Bailey Robert J. , Demetris Anthony J. , Starzl Thomas E. , Murase Noriko
Published: April 2006

Organ allografts have been shown to provide a syngeneic microenvironment for organ-based donor hematopoietic stem cells to maintain long-lasting chimerism after transplantation. We hypothesized that organ allografts would also support engraftment and hematopoiesis of adjunctively infused donor marrow stem cells, syngeneic to organ grafts, in nonmyeloablated recipients. In BN-to-LEW and GFP-to-ACI rat combinations, donor bone marrow (BM) infusion together with small intestine transplantation (SITx) under short-course tacrolimus immunosuppression resulted in persistent macrochimerism (more than 5%) for 150 days. In contrast, after BM infusion or SITx alone, chimerism was temporary and disappeared by day 100. Y-chromosome polymerase chain reaction (PCR) in sex-mismatched male BM plus female intestine or female BM plus male intestine transplantation into female recipients suggested that persistent macrochimerism was derived from infused BM. BM infusion together with lymphoid-depleted intestine grafts also supported macrochimerism development; however, third-party intestine grafts did not. After GFP-positive BM plus wild-type (WT) SITx into ACI, large numbers of GFP-positive leukocytes were found in WT intestine grafts. Isolated cells from WT intestine grafts developed GFP-positive CFU-Cs and propagated multilineage GFP-positive leukocytes when adoptively transferred into lethally irradiated WT recipients. These findings suggest that intestine allograft supports simultaneously infused donor (syngeneic to organ grafts) marrow stem cell engraftment, differentiation, and persistence of chimerism.
Dendritic cells in pathogen recognition and induction of immune responses: a functional genomics approach
Authors: Foti Maria , Granucci Francesca , Pelizzola Mattia , Beretta Ottavio , Ricciardi-Castagnoli Paola
Published: April 2006

At the 38th Annual Meeting of the Society for Leukocyte Biology held in Oxford this year, the biology of dendritic cells (DCs) and macrophages was discussed. In particular, functional genomics approaches were presented to investigate transcriptional changes during microbe and phagocytes interactions. Here, we report functional genomics studies likely to be of interest to the Journal of Leukocyte Biology readers with a particular emphasis on DC biology. DCs are professional antigen-presenting cells, which are essential for the initiation and regulation of natural killer, T, and T rgulatory cell responses. Immature DCs, resident in peripheral sites, are specialized in antigen capture and continually sample soluble and particulate antigens in their local environment. DCs express receptors for cytokines, chemokines, endogenous danger signals, and microbial structures. The interactions between DCs and microorganism are complex, but progress in the past few years has shed light on several aspects of these processes. Infectious disease is the result of an intimate relationship between pathogens and hosts. Thus, understanding the cross-talk between host and pathogen is essential to improve our knowledge of infectious disease. Functional genomics and proteomics applied to DCs and macrophage biology are now providing powerful tools to dissect, at the molecular level, host-pathogen interactions.
Community pharmacists and depression: the pharmacist as intermediary between patient and physician
Authors: Landers M , Blenkinsopp A , Pollock K , Grime J
Published: April 2006

Objectives

To describe community pharmacists' experiences and contributions to the management of mild to moderate depression in primary care and to explore their interactions with patients and physicians.

Method

Qualitative semi-structured interview study with a purposive sample of 20 community pharmacists from a range of backgrounds in one area of England. Pharmacists were asked to describe their involvement in the management of depression from patients' self-diagnosis and self-treatment through to treatment with antidepressants. They were asked to cite examples of the questions that they were asked by patients about depression and its treatment, and about their practice in advising patients with first-time and repeat prescriptions for antidepressants. Attitudes and practice relating to compliance and concordance with antidepressants were explored.

Key findings

Pharmacists were asked a wide range of questions by patients about antidepressants and depression. Often these questions posed ethical dilemmas for the pharmacists by raising topics that crossed inter-professional boundaries. Pharmacists generally saw their role as encouraging patients to take antidepressant treatment and they reported providing technical information, mainly when the first prescription was dispensed. Most pharmacists worked from a “compliance” model although this appeared to conflict sometimes with their own views about the appropriateness of antidepressant treatment. Pharmacists rarely entered into discussion with patients on their feelings about treatment or their intention to take it. Monitoring of compliance to antidepressants was largely seen as the province of the physician and pharmacists appeared to feel unable to undertake this role effectively. Nevertheless 17 of the pharmacists expressed a wish to extend their role in the management of depression.

Conclusions

Pharmacists' accounts showed that patients have unmet needs in relation to the management of depression and treatment with antidepressants. Achieving concordance in the tripartite relationship between patient, GP and pharmacist poses considerable challenges. However, our findings suggest that pharmacists could play a larger role as first-line advisers on depression and its treatment if the identified barriers can be overcome.
Patient receipt of, and preferences for receiving, antidepressant information
Authors: Sleath Betsy , Wurst Keele
Published: April 2006

Objective

The purpose of the study was to examine patient receipt of, and preferences for receiving, antidepressant information.

Method/setting

The study had a cross-sectional design. Eight community pharmacies in central North Carolina participated in the study. Eighty-three English-speaking patients who were picking up antidepressant prescriptions were interviewed by a research assistant. The main outcome measures included: patient receipt of verbal antidepressant information; the number and type of educational messages contained in the written antidepressant leaflets that patients received; the percentage of patients who had a reading level below the reading level of the antidepressant information leaflet; whether patients reported reading the leaflets and how satisfied they were with the leaflets; and how patients preferred to receive antidepressant information.

Key findings

Seventeen per cent of patients did not receive verbal information about how long the medication would take to work from anyone. Only 50 per cent of patients were told what to do if a major side effect occurred. Almost 11 per cent of patients had a reading level below the level of the written pharmacy antidepressant information leaflet. Just over one-third (36 per cent) of patients preferred to receive only written antidepressant information. Less educated patients were significantly more likely to want to receive antidepressant information verbally. Of those patients who preferred to receive verbal antidepressant information or both verbal and written information, 92 per cent chose pharmacists as their first or second choice for providing them with verbal information.

Conclusion

The majority of patients taking antidepressants want to receive verbal information and view pharmacists as an important source of information. Pharmacists have the potential to improve antidepressant adherence if they take the time to educate patients verbally about their medications.
Practice-based pharmaceutical services: a systematic review
Authors: Fish Alison , Watson Margaret C , Bond Christine M
Published: April 2006

Background

General practice-based pharmaceutical services are increasingly common, ranging from global medication changes (eg, generic switch) to individual patient medication review and educational interventions.

Aim

To conduct a systematic review of the effectiveness of practice-based pharmaceutical interventions.

Design

A systematic review of general practice-based pharmaceutical services.

Setting

General practice in the UK, Australia, Canada, Scandinavia and the US.

Outcome measures

The effect and cost of practice-based pharmaceutical services.

Methods

Electronic databases were searched and pharmaceutical organisations were contacted. Studies fulfilling the review criteria were considered for inclusion. Duplicate independent data screening and abstraction was undertaken. Three indicators were used to assess the quality of included studies: method of random allocation; allocation concealment; and proportion of subjects followed to the end of the study.

Results

A total of 2,707 references were identified: 256 full publications were retrieved and 16 randomised, controlled trials (RCTs) met the inclusion criteria. Included studies assessed either the professional interface (educational outreach and general prescribing advice) or the patient interface (medication review and patient-specific prescribing advice). Three trials included all three quality markers. Most studies were effective in achieving one or more of the desired outcomes from pharmaceutical intervention. Two trials showed no statistically significant differences between the study and control groups post intervention.

Conclusions

Many evaluations of practice-based pharmaceutical s***érvices have been published but few meet recognised standards of trial methodology. The results of this review suggest that practice-based pharmaceutical services are effective in achieving desired changes; however, more robust evidence is needed to confirm whether they are effective, efficient and sustainable.
Identification of regulators of germ layer morphogenesis using proteomics in zebrafish
Authors: Link Vinzenz , Carvalho Lara , Castanon Irinka , Stockinger Petra , Shevchenko Andrej , Heisenberg Carl-Philipp
Published: April 2006

During vertebrate gastrulation, a well-orchestrated series of morphogenetic changes leads to the formation of the three germ layers: the ectoderm, mesoderm and endoderm. The analysis of gene expression patterns during gastrulation has been central to the identification of genes involved in germ layer formation. However, many proteins are regulated on a translational or post-translational level and are thus undetectable by gene expression analysis. Therefore, we developed a 2D-gel-based comparative proteomic approach to target proteins involved in germ layer morphogenesis during zebrafish gastrulation. Proteomes of ectodermal and mesendodermal progenitor cells were compared and 35 significantly regulated proteins were identified by mass spectrometry, including several proteins with predicted functions in cytoskeletal organization. A comparison of our proteomic results with data obtained in an accompanying microarray-based gene expression analysis revealed no significant overlap, confirming the complementary nature of proteomics and transcriptomics. The regulation of ezrin2, which was identified based on a reduction in spot intensity in mesendodermal cells, was independently validated. Furthermore, we show that ezrin2 is activated by phosphorylation in mesendodermal cells and is required for proper germ layer morphogenesis. We demonstrate the feasibility of proteomics in zebrafish, concluding that proteomics is a valuable tool for analysis of early development.
Endocytosis of GABAB receptors modulates membrane excitability in the single-celled organism Paramecium
Authors: Ramoino Paola , Gallus Lorenzo , Beltrame Francesco , Diaspro Alberto , Fato Marco , Rubini Patrizia , Stigliani Sara , Bonanno Giambattista , Usai Cesare
Published: April 2006

GABAB receptors modulate swimming behavior in Paramecium by inhibiting dihydropyridine-sensitive Ca2+ channels via G-proteins. Prolonged occupancy of GABAB receptors by baclofen results in a decrease in GABAB receptor functions. Since changes in the number of cell-surface GABAA receptors have been postulated to be of importance in modulating inhibitory synaptic transmission in neurons, we have studied the cell-surface expression and maintenance of GABAB receptors in P. primaurelia. In this study, we use immunostaining in electron and confocal microscopy to demonstrate that constitutive internalization of GABAB receptors in P. primaurelia is mediated by clathrin-dependent and -independent endocytosis. Indeed, GABAB receptors colocalize with the adaptin complex AP2, which is implicated in the selective recruitment of integral membrane proteins to clathrin-coated vesicles, and with caveolin 1, which is associated with uncoated membrane invaginations. Furthermore, when endocytosis is blocked with hypertonic medium, cytosol acidification, filipin or with a peptide that disrupts the association between amphiphysin and dynamin, the effect of baclofen on swimming is increased. These results suggest that GABAB receptor endocytosis into clathrin-coated and -uncoated vesicles represents an important mechanism in the modulation of swimming behavior in Paramecium.
Reaction of Malonaldehyde with Adenosine. Formation of a Novel Adduct Containing a Dioxazatricycloundecene Residue in the Base-pairing Region
Authors: Seto Hiroshi , Seto Takako , Nagakura Koichi , Koike Hiroshi
Published: April 2006

Reaction of malonaldehyde with adenosine at pH 4.5 gave three major adducts including a novel one containing diastereomeric dioxazatricycloundecene residue, formed by addition of three malonaldehyde units.
Aerobic Epoxidation of Olefins Catalyzed by Cobalt(II) Complex Using Propionaldehyde Diethyl Acetal as a Reductant
Authors: Mukaiyama Teruaki , Yorozu Kiyotaka , Takai Toshihiro , Yamada Tohru
Published: April 2006

In the presence of bis(3-methyl-2,4-pentanedionato)cobalt(II) complex catalyst, various trisubstituted olefins are smoothly monooxygenated into the corresponding epoxides in high yields under neutral conditions by the combined use of molecular oxygen and propionaldehyde diethyl acetal.
Porphyrin Synthesis Using Clays. Taking Advantage of Statistical Product Distributions
Authors: Laszlo Pierre , Luchetti Jean
Published: April 2006

Solid acids such as the K10 montmorillonite are useful for preparation of porphyrins from pyrrole condensed with aldehydes. Combining the use of two different aldehydes A and B with unequal, statistical proportions of A and B allows maximization of the relative amount of the desired mixed porphyrin.
Ultrasound-Promoted Synthesis of Arylzinc Compounds Using Zinc Powder and Their Application to Palladium(0)-Catalyzed Synthesis of Multifunctional Biaryls
Authors: Takagi Kentaro
Published: April 2006

Arylzinc compounds containing electron-withdrawing groups such as CO2CH3, CON(CH3)2, CN, Br, Cl, or CF3 at ortho position were prepared readily by the ultrasound-promoted reaction of aryl iodides with zinc powder, which were applied to palladium(0)-catalyzed cross-coupling with aryl halides to afford unsymmetrical and multifunctional biaryls in good yields.
Fe(CO)5/Sulfur-Catalyzed Liquefaction of Yallourn Coal in the Presence of Alcohol and Carbon Monoxide
Authors: Watanabe Yoshihisa , Kawasaki Nori-aki , Yamada Hiro-aki , Wada Kenji , Mitsudo Take-aki
Published: April 2006

Iron/sulfur-catalyzed liquefaction of Yallourn coal using alcohol-carbon monoxide has been investigated. Pentacarbonyliron (Fe(CO)5)/sulfur was found to be an excellent catalyst precursor. In the Fe(CO)5/sulfur catalyzed liquefaction (375 °C-120 min) of Yallourn coal, high conversion (99.5%) was achieved in the presence of ethanol and CO.
Beckmann Rearrangement Catalyzed by the Combined Use of Tetrabutylammonium Perrhenate(VII) and Trifluoromethanesulfonic Acid
Authors: Narasaka Koichi , Kusama Hiroyuki , Yamashita Yuko , Sato Hiroshi
Published: April 2006

Beckmann rearrangement of oximes is catalyzed with tetrabutylammonium perrhenate(VII), trifluoromethanesulfonic acid and hydroxylamine hydrochloride in nitromethane under azeotropic conditions, giving amides in high yield.
Synthesis and Antitumor Activity of [3-Acetyl-2,4(3H,5H)-furandionato-O3,O4] [(1R,2R)-cyclohexanediamine]platinum(1+) Ion Complex and Its Derivatives
Authors: Hata Go , Kawai Hideki , Kaneko Tatsuya , Imaoka Takayuki , Kitano Yukishige , Mutoh Masato , Imanishi Hideyo
Published: April 2006

The reaction of dihydroxo[(1R,2R)-cyclohexanediamine]platinum(II) with 3-acetyl-2,4-(3H,5H)-furandiones gave salts consisting of [3-acetyl-2,4(3H,5H)-furandionato-O3,O4] [(1R,2R)-cyclohexanediamine]platinum(1+) ions and enolates of 3-acetyl-2,4-(3H,5H)-furandiones. The complexes show high solubility, and antitumor activity at low doses against murine leukemia L1210 sensitive and resistant to cis-dichlorodiammineplatinum(II).
Intermolecular Ferromagnetic Interaction of 4-(2-Naphthylmethyleneamino)-2,2,6,6-tetramethylpiperidin-1-oxyl
Authors: Tomioka Katsuyuki , Ishida Takayuki , Nogami Takashi , Iwamura Hiizu
Published: April 2006

The magnetic susceptibility and magnetization of a polycrystalline sample of the title compound were measured on a Faraday balance and a SQUID susceptometer. The intermolecular ferromagnetic interaction was indicated by the facts that the χmolT value increased with decreasing temperature and that the magnetization measured at 1.7 and 4.2 K saturated more rapidly than that of a Brillouin function with S = 1/2.
A Convenient Method for Synthesis of 1-Amino-2-tetralones by Photoamination of 2-Alkoxynaphthalenes with Alkylamines
Authors: Yamashita Toshiaki , Yamano Katsuhiko , Yasuda Masahide , Shima Kensuke
Published: April 2006

Irradiation of an acetonitrile-water solution containing 2-alkoxynaphthalene, an amine, and m-dicyanobenzene gave selectively 2-alkoxy-1-alkylamino-1,4-dihydronaphthalenes in relatively good yields. The aminodihydronaphthalenes were acetylated with Ac2O and then treated with BF3·OEt2 to give N-acetyl-1-alkylamino-2-tetralones in good yields.
A New Synthetic Route to β-Hydroxythioethers from Carbonyl Compounds Using Samarium(II) Diiodide (SmI2)
Authors: Yamashita Masayuki , Kitagawa Kazuhiro , Ohhara Takashi , Iida Yoshiko , Masumi Akiko , Kawasaki Ikuo , Ohta Shunsaku
Published: April 2006

In the presence of samarium diiodide (SmI2) in THF, chloromethyl sulfides reacted with carbonyl compounds to give β-hydroxythioethers under mild and neutral conditions in moderate to good yields.
Novel Photo-Memory Effect in Photoconductivity of Conducting Polymer Containing Photochromic Dye
Authors: Kawai Tsuyoshi , Koshido Takashi , Nakazono Masahiro , Yoshino Katsumi
Published: April 2006

Photoconduction of a conducting polymer, poly(9,9-dihexadecylfluorene) containing a photochromic dye, cis-1,2-dicyano-1,2-bis(2,4,5-trimethyl-3-thienyl)ethene, is suppressed upon photoisomerization of the dye from ring-open form to ring-closed form but recovered by the reverse photoisomerization. The reversible memory effect in the photoconduction has been discussed on the basis of the energy states of the dye and those trapping effects on the photo-carriers in the conducting polymer.
Trioxygen-Bridged Porphyrin Dimers with Unusual Molecular Geometries. X-Ray Crystal Structures of {(μ-OH)3[Zr(OEP)]2}(7,8-C2B9H12) and (μ-O)(μ-OH)2[Zr(TPP)]2
Authors: Kim Hee-Joon , Whang Dongmok , Do Youngkyu , Kim Kimoon
Published: April 2006

The X-ray structures of the title complexes revealed that the two zirconium porphyrin moieties are joined either by three bridging hydroxo ligands or by one oxo and two hydroxo ligands. In both structures, the two porphyrin macrocycles are perfectly or nearly eclipsed and concomitantly one of the Zr-O bonds eclipses one of the Zr-N bonds. Such unprecedented eclipsed conformation found in both structures strongly suggests that it is stabilized by dπ-pπ interactions between Zr and O and N atoms despite the unfavorable steric interactions.
Synthesis of ortho-Acylbenzylboronates via Cross-Coupling Reaction of (Dialkoxyboryl)methylzinc Reagents with Haloarenes. A Stable ortho-Quinodimethane Precursor
Authors: Kanai Gen , Miyaura Norio , Suzuki Akira
Published: April 2006

The cross-coupling reaction of IZnCH2B(OCMe2) with iodoarenes in the presence of PdCl2(PPh3)2 produces the corresponding benzylic boronates in high yields. Among them, the benzylic boronates having an acyl group at the ortho position readily undergo the 1,5-rearrangement to the carbonyl oxygen producing the o-quinodimethane derivatives under thermal or photochemical conditions. The reaction provides benzo-fused cycloalkanes by trapping with dienophiles.
Structure of Nonplanar Octabromotetraphenyl Porphyrin and Kinetics of Rapid Metalation Reactions
Authors: Bhyrappa Puttaih , Nethaji Munirathinam , Krishnan Varadachari
Published: April 2006

Octabromotetraphenylporphyrin adopts a severe saddle-shaped distorted structure owing to the steric crowding of heavy bromine substituents. The rate enhancement of porphyrin metalation reaction is primarily due to the nonplanarity of the ring while the electronic effect diminishes the affinity of the porphyrin towards metal ions.
Synthesis of π-Conjugated Soluble Poly(aryleneethynylene) Type Polymers and Their Properties
Authors: Takagi Masakazu , Kizu Kenichi , Miyazaki Yuichi , Maruyama Tsukasa , Kubota Kenji , Yamamoto Takakazu
Published: April 2006

Pd-catalyzed coupling reactions with dihaloaromatic compounds X-Ar-X and diethynylaromatic compounds HC≡C-Ar′-C≡CH give new soluble π-conjugated polymers when Ar and/or Ar′ group is pyridine-2,5-diyl or has a long chain alkyl substituent.
Iodo-Ligand Substitution of [Pd(pp3)I]+ (pp3 = Tris(2-diphenylphosphinoethyl)phosphine) by Trimethylphosphite. The First Proposition of the Associative Ligand-Substitution Mechanism of Trigonal-Bipyramidal Five-Coordinate Palladium(II) Complex
Authors: Aizawa Sen-ichi , Funahashi Shigenobu
Published: April 2006

The kinetic investigation for the iodo-ligand substitution of [Pd(pp3)I]+ (pp3 = tris(2-diphenylphosphinoethyl)phosphine) by trimethylphosphite in CDCl3 has been performed by 31p NMR spectroscopy. The trigonal-bipyramidal structure of the reactant and product has been confirmed by X-ray analysis and 31p NMR spectra. The associative mode in the activation process is first proposed for the trigonal-bipyramidal palladium(II) complexes.
Ortho-Phenylenedizinc(II) Compounds Ultrasound-Promoted Synthesis from o-Diiodobenzene and Zinc Powder and Its Synthetic Application
Authors: Takagi Kentaro , Shimoishi Yasuaki , Sasaki Ken
Published: April 2006

A facile and efficient synthetic procedure of o-phenylenedizinc(II) compound from o-diiodobenzene and zinc powder under the irradiation of ultrasound is reported. The compound was proved to be a unique reagent supplying o-phenylenedianion of high chemoselectivity. Symmetrically 1,2-diaryl or diaroyl substituted benezenes were obtained in good yields by Pd(0)-catalyzed cross-coupling of the compound with aryl halides or acyl halides.