bluuebunny/crossref_metadata_2025 huggingface dataset:
A QSO survey via optical variability and zero proper motion in the M92 field. V. Completion of the QSO sample
Authors: Meusinger H. , Brunzendorf J. , Laget M.
Published: July 2003

We present results from the spectroscopic follow‐up observation of additional QSO candidates in the variability and proper motion (VPM) survey field around M92. In the previous studies, the VPMsurvey has shown to be an efficient way to select QSOs; the QSO sample was confined to the magnitude range B ≲ 19.8 with a completeness estimated to ∼ 90% for B ≲ 19.5. Here we study the faint end (B > 19.8) of the candidate list and check the completeness of the brighter (B < 19.7) QSO subsample. We first study an additional 34 brighter QSO candidates selected by FOCA UV brightness, radio detection, or optical colours. Only one new QSO was found. We show that a two‐colour search making use of FOCA 2 000 magnitudes efficiently selects QSOs, Seyfert galaxies, and NELGs. However, there is no QSO found from this method which would not have been selected by the VPM method as well. The main aim of this paper is to identify the VPM QSO candidates with 19.8 < B < 20.5. We select 53 candidates of which 50 were observed; 26 QSOs, 2 Sey1, and 2 NELGs were found. The fraction of QSOs and Sey1s among the faint high‐priority candidates amounts to 71%. The whole AGN sample comprises now 123 QSOs and 18 Sey1s. We find that the extended VPM QSO sample does not significantly differ from other optically selected samples with regard to their low‐resolution spectra and optical broad‐band colours.
Angular velocity during the cycle deduced using the sunspot group age selection methodology
Authors: Zuccarello F. , Zappalá R.A.
Published: July 2003

We have used the “age selection methodology” (ASM) (Zappalá and Zuccarello 1991) to study the variability of the sunspot groups angular velocity during the activity cycle. The ASM allows us to separate the contribution of Young Sunspot Groups (YSG) from that of Recurrent ones (RSG) in the Ω(θ) determination and therefore to evaluate whether the increase in angular velocity during minima (reported in literature using all sunspot groups as tracers), is due to a greater statistical weight of YSG on RSG or whether it reflects a global characteristic of the Sun. The results obtained from the analysis of sunspot groups data collected during the period 1874‐1981 (Greenwich Photoheliographic Results) indicate that during minima, besides the fact that the percentage of RSG drops to ≤ 5%, both YSG and RSG show the same increase in angular velocity, i.e. 0.16 degrees/day. Comparing our results with those reported in literature and taking into account the internal angular velocity as deduced by p‐mode oscillations, it is possible to conclude that the observed higher angular velocity of the Sun during minima concerns several layers of the Sun.
Theoretical model of a magnetic white dwarf
Authors: Bednarek I. , Brezina A. , Mańka R. , Zastawny‐Kubica M.
Published: July 2003

In this paper a theoretical model of a magnetic white dwarf is studied. All numerical calculations are performed under the assumption of a spherically symmetric star. The obtained equation of state is stiffer with the increase of value of the magnetic field (B). Numerical values of the maximum mass and radius are presented. The influence of the magnetic field on the results is evident. Finally the departure from the condition of isothermality of a degenerate electron gas in the gravitational field is discussed.
Symbolic analytical solutions for the abundances differential equations of the Helium burning phase
Authors: Nouh M.I. , Sharaf M.A. , Saad A.S.
Published: July 2003

In this paper, a literal analytical solution is developed for the abundances differential equations of the helium burning phase in hot massive stars. The abundance for each of the basic elements 4He,12C,16O and 20Ne is obtained as a recurrent power series in time, which facilitates its symbolic and numerical evaluations. Numerical comparison between the present solution and the numerical integration of the differential equations for the abundances show good agreement.
Astrometric detection of binary companions and planets: Acceleration of proper motion
Authors: Kaplan G.H. , Makarov V.V.
Published: July 2003

Apparent acceleration of proper motion is one of the observable manifestations of orbital motion in binary stars. Owing to the increasing accuracy of astrometric measurements, it may also be a method to detect binarity of stars. This paper presents some analytical expressions for the effects of binary motion on proper motions when the orbital period is at least several times the span of observations. We estimate orbit dimensions and distances at which low‐mass companions and planets may be detected around main‐sequence stars, using preliminary estimates of precision for the AMEX, GAIA and SIM space missions.
Diarrhea: A new risk factor for neural tube defects?
Authors: Felkner Marilyn , Hendricks Kate , Suarez Lucina , Waller D. Kim
Published: July 2003

BACKGROUND

Neural tube defects (NTDs) affect approximately 4000 US pregnancies annually. Folic acid supplementation taken before conception protects against the occurrence of NTDs. Adequate levels of vitamin B12 also appear to play a significant role. Gastrointestinal disturbances, such as those caused by diarrhea, might negatively affect the availability of these vitamins, thereby increasing the risk of these birth defects.

METHODS

To determine whether periconceptional diarrhea increases the risk of NTD‐affected pregnancies, a population‐based case‐control study was conducted in the 14 Texas–Mexico border counties. Information on diarrhea and other risk factors was ascertained by in‐person interview. Study subjects were Mexican‐American women who resided and delivered in any border county during 1995–2000. Case women, identified through active surveillance, had liveborn or stillborn infants or fetuses diagnosed with anencephalus, spina bifida, or encephalocele. Control women were randomly selected from women delivering normal live births in study area health facilities.

RESULTS

One or more episodes of periconceptional diarrhea were associated with increased risk of NTD‐affected pregnancies compared to no episodes of diarrhea (OR = 3.7, 95% CI = 1.8–7.6). This association was independent of fever, obesity, maternal age, maternal birthplace, income, prior unproductive pregnancy, and dietary plus multivitamin folate intake, known risk factors for NTDs.

CONCLUSIONS

Confirmation of this new risk factor might have public health implications due to the feasibility of modifying exposure. Birth Defects Research (Part A) 67:504–508, 2003. © 2003 Wiley‐Liss, Inc.
Low maternal alcohol consumption during pregnancy and oral clefts in offspring: The Slone birth defects study
Authors: Meyer Katie A. , Werler Martha M. , Hayes Catherine , Mitchell Allen A.
Published: July 2003

BACKGROUND

The association between maternal alcohol consumption during pregnancy and oral clefts in offspring remains unclear. We studied this relation in a case–control surveillance study of birth defects.

METHODS

From 1983 to 1997, we recruited 5956 study subjects from greater Boston, Philadelphia, Toronto, and parts of Iowa. The cases were liveborn infants with cleft palate alone (CP; n = 205), cleft lip and palate (CLP; n = 383), cleft lip alone (CL; n = 259), or Pierre‐Robin sequence (n = 65). The controls (n = 4272) were infants who had no oral clefts but had one or more of the following defects: malformations of the digestive tract, reproductive organs, abdominal wall, and respiratory tract; chromosomal anomalies; inguinal hernia; tumors; and Mendelian inherited disorders. Based on maternal reports of alcohol consumption during the first 4 months of pregnancy, we derived average weekly consumption, average number of drinks per drinking day, and the maximum number of drinks consumed in a given day. The mothers also provided data on potential confounding or modifying variables, such as vitamin supplement use.

RESULTS

There was no relation between maternal alcohol consumption during pregnancy and CL or CP. The odds ratios (ORs) for cleft lip with or without palate (CL/P) were 1.0, 1.1, and 0.9 in women who consumed <1.0, 1.0–2.9, and 3.0 + drinks per week, respectively. These findings did not change when we considered possible modifying effects of vitamin supplement use.

CONCLUSIONS

Our findings do not support an association between oral clefts and a low level of alcohol consumption. Birth Defects Research (Part A) 67:509–514, 2003. © 2003 Wiley‐Liss, Inc.
Birth defects in the offspring of non‐Caucasian, non‐Indigenous women in Western Australia
Authors: Kwon Seonghee , Bower Carol , English Dallas
Published: July 2003

BACKGROUND

Birth defects in infants born to non‐Caucasian, non‐Indigenous mothers in Australia have not been described in detail previously.

METHODS

Using data from the Western Australian Maternal and Child Health Research Data Base, an index cohort of all non‐Caucasian, non‐Indigenous mothers giving birth in Western Australia between 1985 and 1995 (n = 17,706 births) was compared with a 10% random sample of births to Caucasian mothers (n = 24,180) over the same period.

RESULTS

Overall, the index mothers had a 21% less risk of having a baby with birth defects (prevalence ratio, 0.79; 95% confidence interval, 0.72–0.86). The six major countries of birth of the index mothers were Vietnam, the Philippines, Singapore, Malaysia, India, and New Zealand. Mothers from Vietnam and the Philippines were significantly less likely to have a baby with a birth defect. The prevalences for the remaining four maternal countries of birth were not significantly different from that in the comparison cohort.

CONCLUSIONS

The difference in risk of birth defects is probably not a result of confounding by maternal age, plurality, parity, socioeconomic status, marital status, or place of residence. However, it may be a real difference or a result of ascertainment bias. Birth Defects Research (Part A) 67:515–521, 2003. © 2003 Wiley‐Liss, Inc.
Antisense modulation of the coding or regulatory sequence of the folate receptor (folate binding protein‐1) in mouse embryos leads to neural tube defects
Authors: Hansen Deborah K. , Streck Randal D. , Antony Asok C.
Published: July 2003

BACKGROUND

Although folic acid decreases the incidence of neural tube defects (NTDs) in humans, the mechanism for this protection is unknown. We have employed antisense technology to alter expression of the gene for the folate receptor (folate binding protein‐1 [Folbp1]) in mouse embryos cultured in vitro.

METHODS

Embryos were explanted on day 8 of gestation and cultured for 44 hr. Several oligodeoxyribonucleotides designed to modulate the coding region or a regulatory sequence in the 5′‐untranslated region of Folbp1 were microinjected into the amniotic sac of embryos at the beginning of the culture period.

RESULTS

Two different antisense sequences to the 5′ and 3′ coding region in Folbp1 produced concentration‐dependent increases in the number of embryos with NTDs. Coinjection of 5‐methyltetrahydrofolate with these sequences decreased the frequency of abnormal embryos. A semi‐quantitative RT‐PCR technique used to measure the amount of Folbp1 mRNA in treated and control embryos confirmed that the mRNA level was decreased by treatment with the antisense sequences. An antisense oligodeoxyribonucleotide to a 17 base cis regulatory element also generated a concentration‐dependent increase in the frequency of embryos with NTDs, and a decrease in the level of Folbp1 mRNA.

CONCLUSIONS

These results demonstrate that alterations in expression of Folbp1 by perturbing either the coding sequence or a critical regulatory cis‐element can play a role in NTDs. Birth Defects Research (Part A) 67475–487, 2003. © 2003 Wiley‐Liss, Inc.
A Curriculum‐Based Classification System for Community Colleges
Authors: Schuyler Gwyer
Published: July 2003

The author proposes and tests a community college classification based on curricular characteristics and their association with institutional characteristics. The analysis seeks readily available data correlates to represent the percentage of a college's course offerings that are in the liberal arts. A simple two‐category classification system using total enrollment is ultimately found to be the most accurate.
Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopecia
Authors: Seligson Allen L , Campion Brian K , Brown Jason W , Terry Ron C , Kucerova Renata , Bienova Martina , Hajduch Marian , Sovak Milos
Published: July 2003

Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3‐amino‐2‐hydroxy‐2‐methyl‐N‐(4‐nitro‐3‐trifluoromethyl)phenyl) propanamide (BP‐34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 μM decreased expression of the AR in LNCaP human cells by 95%, its serum half‐life was 6 h; it decomposes hydrolytically to BP‐34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270–300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD50 in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double‐blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP‐34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292–306, 2003. © 2003 Wiley‐Liss, Inc.
Optimization of drug release from dermatological semisolid preparations
Authors: Eros István , Abu‐Eida Ehab Youseff , Csóka Ildikó , Sánta Zsuzsa , Cserne Annamária , Kövér Tünde
Published: July 2003

The aim of the present study was to optimize the process of drug release. Factors which influence drug release were studied in detail and their effects were described numerically. The factors studied were as follows: the concentration of the pharmacon (salicylic acid); its particle size; its suspended, dissolved, solubilized, or molecular encapsulated state;, the composition of the vehicle; the quantities of the polar and apolar components; and the viscosity of the vehicle. Drug release studies were carried out with Hanson's vertical diffusion cell. The process was described quantitatively by the slope of the equation describing the time‐course of the liberation, by the quantity of pharmacon liberated in 8 h and also by the optimization parameter determined on the basis of the 22 model of the factorial design method. Increase of the concentration of salicylic acid was found to be accompanied by an exponential rise in drug release, while the extent of liberation decreased linearly with increasing viscosity. The greatest increase in the optimization parameter was observed when the polarity of the vehicle was changed. The process of liberation consists of the following steps: dissolution of the pharmacon, diffusion of the dissolved molecules, and their distribution. The current data revealed that the distribution is the most important element and exerts the greatest influence on optimal drug release. Drug Dev. Res. 59:316–325, 2003. © 2003 Wiley‐Liss, Inc.
Ventricular PKC‐ϵ and humoral signaling in DOCA‐Salt rats treated with labedipinedilol‐A
Authors: Yeh Jwu‐Lai , Liang Jyh‐Chong , Liou Shwu‐Fen , Lin Young‐Tso , Sheu Sheng‐Hsiung , Lai Wen‐Ter , Shin Shyi‐Jang , Chen Ing‐Jun
Published: July 2003

Effects of oral antihypertensive monotherapy with labedipinedilol‐A, labetalol, atenolol, amlodipine, prazosin (20 mg kg−1 day−1), and short‐acting nifedipine (3 mg kg−1 day−1) on DOCA‐salt‐induced translocation of ventricular protein kinase C‐ϵ(PKC‐ϵ), humoral signaling, and the cardiovascular system were investigated in rats for 4 weeks. The triple blocking activities of labedipinedilol‐A (α/β‐adrenoceptor blockade and calcium entry blockade) were compared with single blocking activities of selective drugs. Cytosolic PKC‐ϵ immunoreactivity was decreased by labedipinedilol‐A, short‐acting nifedipine, amlodipine, prazosin, labetalol, atenolol, and losartan. Membranous PKC‐ϵ immunoreactivity was significantly decreased by labedipinedilol‐A, amlodipine, prazosin, labetalol, and atenolol. Labedipinedilol‐A and prazosin more potently decreased membranous than cytosolic PKC‐ϵ expression. Labedipinedilol‐A, labetalol, and atenolol effectively inhibited DOCA‐salt‐induced increases in angiotensin II (Ang II). All antihypertensive agents reduced endothelin‐1 (ET‐1) levels in urine and cardiac weight growth. Treatments with labedipinedilol‐A, labetalol, atenolol, and amlodipine normalized DOCA‐salt‐induced ANP increases. Prazosin did not decrease ANP. Short‐acting nifedipine elevated ANP. During long‐term antihypertensive therapy in DOCA‐salt hypertensive rats, single blockade drugs did not fully inhibit ventricular PKC‐ϵ translocation or Ang II, ET‐1, and ANP humoral signaling. However, triple blockade labedipinedilol‐A therapy had a wide range of α/β‐adrenergic receptor and calcium channel inhibitory activities, including diminished reflux tachycardia, inhibition of PKC‐ϵ translocation, and reduction of Ang II, ET‐1, and ANP formation. Drug Dev. Res. 59:307–315, 2003. 2003 Wiley‐Liss, Inc.
Subacute toxicity of all‐trans‐retinoic acid loaded biodegradable microspheres in rats
Authors: Choi Yongdoo , Lee Chulkyu , Park Kyeongsoon , Kim Sang Yoon , Kim Sun Hee , Han Shin , Kim Sung Hyun , Byun Youngro
Published: July 2003

Biodegradable microspheres containing all‐trans‐retinoic acid (atRA) were prepared previously to enhance the clinical efficacy of atRA for chemoprevention. In this study, subacute toxicity of atRA in sustained release was evaluated after subcutaneous administration of 0, 25, 50, and 100 mg atRA/kg of atRA‐loaded microspheres. After the subcutaneous injection of atRA‐loaded microspheres, the atRA concentration in plasma was maintained in the range of 3.5–25 ng/ml for 2–3 weeks. When 100 mg atRA/kg was administered, the atRA concentration in plasma was maintained at levels greater than 10 ng/ml and severe toxic effects were observed. When the dose of 50 mg atRA/kg was administered, the plasma concentration of atRA was maintained below 10 ng/ml over 3 weeks and only mild signs of toxicity were observed. Therefore, it was concluded that the dosage of atRA‐loaded microspheres should be less than 50 mg atRA/kg for chemopreventive applications against carcinogenesis. Considering recovery from intoxication, the optimum interval for repeated injection of the microspheres was suggested to be over 4 weeks. In addition, it was found that the atRA concentration in plasma should be controlled below 10 ng/ml to minimize toxic effects of atRA. Drug Dev. Res. 59:326–332, 2003. © 2003 Wiley‐Liss, Inc.
TNF‐α  mediates the induction of nitric oxide synthase in macrophages but not in neutrophils in experimental cutaneous leishmaniasis
Authors: Fonseca Simone G. , Romão Pedro R. T. , Figueiredo Florêncio , Morais Ruth H. , Lima Hermênio C. , Ferreira Sérgio H. , Cunha Fernando Q.
Published: July 2003

Leishmania major infection in C57BL/6 mice is controlled by the activation of a Th1 response and nitric oxide (NO) production by macrophages. TNF‐α is considered one of the most important cytokines involved in this response. In the present study, we investigated the expression of nitric oxide synthase (iNOS) in the inflammatory cells present in the lesion and draining lymph nodes, and the cytokine production by lymph node cells in animals treated with anti‐TNF‐α. Our results demonstrated that mice treated with anti‐TNF‐α presented an increase in the number of parasites and the size of lesion, but they were able to control the infection. The increase in the lesion size correlated to the reduction of iNOS activity in the draining lymph nodes. Furthermore, the anti‐TNF‐α treatment also reduced the expression of iNOS in the macrophages, but did not affect the iNOS expression in the neutrophils. The anti‐TNF‐α mAb did not reduce the iNOS expression in IFN‐γ‐stimulated L. major infected neutrophils in vitro. Anti‐TNF‐α mAb treatment caused an increase in the production of IFN‐γ and IL‐10 by the lymph node cells from infected mice. Consequently, these results suggest that neutrophils do not respond to anti‐TNF‐α treatment and might be a source of NO to control L. major infection under these experimental conditions.
Possible involvement of glial cell line‐derived neurotrophic factor and its receptor, GFRα1, in survival and maturation of thymocytes
Authors: Kondo Sachiko , Kishi Hiroyuki , Tokimitsu Yoshiharu , Muraguchi Atsushi
Published: July 2003

The glial cell line‐derived neurotrophic factor (GDNF) and its receptors (GFR) play important roles in the promotion of survival and differentiation of central and peripheral neuronal populations. We show that GFRα1, a component of GDNF receptor, was expressed in thymocytes at an early stage of thymocyte‐development and was involved in the survival of thymocyte precursors. GFRα1and GDNF were expressed in thymus, but not in spleen or lymph nodes in adult mice. During embryonic thymocyte development, GFRα1 was predominantly expressed on thymocytes from days 14.5 to 16.5 of gestation, and thereafter its expression gradually declined. In adult thymus, GFRα1 was expressed only on CD4–CD8– double‐negative (DN) thymocytes, but not on CD4+CD8+ double‐positive or single‐positive thymocytes. It was strongly expressed on RAG2–/– thymocytes arrested at the DN stage, and ist expression was reduced during their differentiation after in vivo anti‐CD3 antibody stimulation. Additionally, fetal thymocyte precursors grew in serum‐free medium of the fetal thymus organ culture system in the presence of recombinant GDNF (rGDNF), while the cells without rGDNF died. These results suggested that GDNF/GFRα1 are involved in the survival of both the nervous system and DN immature thymocytes.
N‐terminal destruction signals lead to rapid degradation of the major histocompatibility complex class II transactivator CIITA
Authors: Schnappauf Felix , Hake Sandra B. , Carvajal Margarita M. Camacho , Bontron Séverine , Lisowska‐Grospierre Barbara , Steimle Viktor
Published: July 2003

Major histocompatibility complex (MHC) class II molecules play an essential role for the cellular immune response by presenting peptide antigens to CD4+ T cells. MHC class II molecules and genes show a highly complex expression pattern, which is orchestrated through a master regulatory factor, called CIITA (class II transactivator). CIITA controls MHC class II expression not only qualitatively, but also quantitatively, and has therefore a direct influence on the CD4 T cell‐dependent immune response. CIITA is itself tightly regulated not only on the transcriptional level, but as we show here also on the protein level. CIITA is subjected to a very rapid protein turnover and shows a half‐life of about 30 min. Inhibition of degradation by proteasome inhibitors and the identification of ubiquitylated CIITA intermediates indicate that the degradation of CIITA is mediated by the ubiquitin‐proteasome system. We identified two regions mediating degradation within the N‐terminal domain of CIITA. N‐terminal fusions or deletions stabilized CIITA, indicating that the N termini contribute to degradation. Several non‐functional CIITA mutants are partially stabilized, but we provide evidence that transcriptional activity of CIITA is not directly linked to degradation.
Induction of arthritis by single monoclonal IgG anti‐collagen type II antibodies and enhancement of arthritis in mice lacking inhibitory FcγRIIB
Authors: Nandakumar Kutty Selva , Andrén Maria , Martinsson Pernilla , Bajtner Estelle , Hellström Silvia , Holmdahl Rikard , Kleinau Sandra
Published: July 2003

IgG anti‐collagen type II (CII) antibodies (Ab) can induce arthritis in healthy mice. Here we have investigated if single monoclonal IgG anti‐CII Ab can induce arthritis in CIA‐susceptible DBA/1 mice and if there is an IgG subclass dependency. The involvement of Fc receptors for IgG (FcγR) in anti‐CII Ab‐mediated arthritis was also investigated by comparing the clinical outcome in DBA/1 mice to those in FcγR‐deficient mice. We demonstrate for the first time that single mAb to naive DBA/1 mice can induce persistent arthritis. Histology of the inflamed joints revealed massivecellular infiltrate and cartilage and bone destruction. All IgG subclasses tested (IgG1, IgG2a and IgG2b) were arthritogenic, with the IgG1 and IgG2b isotypes as the dominating arthritogenic Ab. Pathogenicity was dependent on engagement of activating FcγR, as FcRγ‐deficient mice were completely resistant to Ab‐mediated arthritis. The arthritis induced with the IgG1 and IgG2b Ab was also inhibited by FcγRIII disruption, whereas arthritis mediated by the IgG2a Ab was not substantially affected. The arthritic response of the IgG1 and IgG2b isotypes, but not of the IgG2a Ab, was further enhanced in mice lacking the inhibitory FcγRIIB. These results demonstrate that single IgG anti‐CII mAb can induce erosive arthritis and that IgG anti‐CII Ab mediate arthritis by engagement of FcγR.
Cyclic AMP increases endogenous granulocyte colony‐stimulating factor formation in monocytes and THP‐1 macrophages despite attenuated TNF‐α formation
Authors: Hareng Lars , Meergans Thomas , von Aulock Sonja , Volk Hans‐Dieter , Hartung Thomas
Published: July 2003

The cytokine granulocyte colony‐stimulating factor (G‐CSF) is in broad clinical use to treat neutropenia, and trials on its use in immunosuppressed conditions and infections are ongoing. To aply G‐CSF effectively, it is crucial to understand the regulation and distribution of its endogenous formation. Since G‐CSF release is mediated, at least in part, by TNF‐α formation, we investigated whether drugs suppressing TNF‐α also impair G‐CSF production. Surprisingly, G‐CSF formation was enhanced in lipopolysaccharide (LPS)‐stimulated blood from a pentoxifylline‐treated patient. In the presence of dibutyryl‐cAMP, forskolin, tolafentrine or 3‐isobutyl‐1‐methylxanthine, LPS‐induced G‐CSF formation was enhanced in THP‐1 cells, primary monocytes and whole blood. Correspondingly,rp‐8‐bromo‐cAMP suppressed LPS‐induced G‐CSF release. Addition of prostaglandin E2 enhanced and indomethacin suppressed G‐CSF formation. Reporter gene studies showed that dibutyryl‐cAMP enhanced LPS‐induced G‐CSF promoter activity, indicating a transcriptional up‐regulation. Furthermore, disruption of a newly identified putative cAMP‐responsive element (CRE) in the G‐CSF promoter demonstrated the regulatory role for G‐CSF gene transcription. In conclusion, endogenous G‐CSF formation critically depends on both TNF‐α and cyclooxygenase products, exerting effects via cAMP and the CREin the G‐CSF promoter. This might have bearing for drug side effects, putative G‐CSF mimetics and our understanding of G‐CSF immunobiology.
The effects of B7‐dependent costimulation on T cell division and survival in vivo and in vitro are dependent on antigen concentration
Authors: Lumsden Joanne M. , Prasad Simon J. , Peach Robert J. , Ronchese Franca
Published: July 2003

We used 5‐(and 6‐) carboxyfluorescein diacetate succinimidyl ester labeled TCR‐transgenic CD4+ T cells to investigate the contribution of B7 costimulation to T cell activationand clonal expansion. B7 costimulation was blocked with the fusion protein cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4)‐Ig, which prevents the interaction of B7 with its receptor CD28 on T cells. CTLA4‐Ig had different effects depending on the density of antigen (Ag)/MHC ligands available by T cells. In the presence of CTLA4‐Ig, tenfold higher concentrations of Ag were required for T cells to undergo cell division in vitro. At high Ag concentrations, T cell division occurred at comparable rates whether in the presence or absence of CTLA4‐Ig; however, T cell survival and clonal expansion were strongly inhibited. Addition of IL‐2 restored T cell survival but not responsiveness to low doses of Ag. In vivo, B7 costimulation was similarly required for the survival of Ag‐specific T cells but not for cell division in response to high amounts of Ag. Thus, B7 costimulation regulates CD4+ T cell responses by promoting cell division in the presence of limiting amounts of Ag, and by protecting T cells from the onset of apoptosis.
Mechanism(s) promoting HIV‐1 infection of primary unstimulated T lymphocytes in autologous B cell/T cell co‐cultures
Authors: Döpper Susanne , Wilflingseder Doris , Prodinger Wolfgang M. , Stiegler Gabriele , Speth Cornelia , Dierich Manfred P. , Stoiber Heribert
Published: July 2003

Resting CD4+ T cells in the lymphoid tissue (LT) are essential producers of virions at the beginning of HIV infection in vivo. We previously developed a model that allowed in vitro infection of non‐prestimulated T lymphocytes in the presence of autologous B lymphocytes and complement. In this study, we try to clarify the mechanism(s) responsible for virus transmission in unstimulated autologous B cell/T cell co‐cultures. Ex vivo analyses of patient plasma samples revealed that HIV was opsonized. Flow cytometry showed that opsonized virus preferentially bound to complement receptor (CR)‐2 on B lymphocytes in primary B cell/T cell co‐cultures. As indicated by cytokine measurements and transwell experiments, soluble factors seemed to play a minor role in enabling infection. Rather, direct interaction between B and T lymphocytes and direct binding of opsonized virus to CR2 on B cells turned out to be essential for productive infection. Antibodies blocking cell‐cell adhesion inhibited p24 antigen production. An anti‐CR2 antibody blocking C3d‐CR2 binding also significantly reduced viral replication. Since the infection of unstimulated T cells by opsonized primary HIV isolates in the presence of B cells was highly efficient independent of the tropism of the virus, this mechanism may be critical in the pathogenesis of HIV.
A minimal human immunostimulatory CpG motif that potently induces IFN‐γ and IFN‐α production
Authors: Fearon Karen , Marshall Jason D. , Abbate Christi , Subramanian Sandhya , Yee Priscilla , Gregorio Josh , Teshima Glen , Ott Gary , Tuck Stephen , Van Nest Gary , Coffman Robert L.
Published: July 2003

Recent reports have shown that immunostimulatory sequences (ISS) containing CpG motifs have minimal length requirements (≥12 bases) for the exertion of immune‐enhancing function upon mammalian cells. Herein we demonstrate that short ISS (5–7 bases), which exhibit no activity on their own, induce IFN‐γ and IFN‐α secretion from human peripheral blood mononuclear cells when adsorbed to the surface of cationic poly(D,L‐lactide‐co‐glycolide) microparticles (cPLGA). Utilizing this technique, we discovered a minimal ISS sequence for induction of IFN‐γ and IFN‐α from human cells: 5′‐TCGXX‐3′. These short ISS/cPLGA formulations targeted PDC in similar fashion to longer ISS ODN, the activity of which does not require (but is enhanced by) cPLGA. PDC stimulated with short ISS/cPLGA responded with enhanced uptake of ISS and elevated production of cytokines, including IFN‐α. However, ISS‐responsive B cells did not respond to short ISS/cPLGA, underlining the plasmacytoid dendritic cell selectivity of this formulation. These results describe a novel technique for formulating active, but very short, ISS oligodeoxynucleotide that allows for the dissection and characterization of minimal immunostimulatory CpG motifs.
Germ‐line transcription occurs on both the functional and the non‐functional alleles of immunoglobulin constant heavy chain genes
Authors: Delpy Laurent , Le Bert Marc , Cogné Michel , Khamlichi Ahmed Amine
Published: July 2003

In B cells undergoing class switching, recombination is usually directed to the same switch sequences on both homologous chromosomes and is generally preceded by germ‐line transcription initiated from I promoters upstream of immunoglobulin constant heavy chain genes. Whether germ‐line transcription occurs on both alleles or is restricted to the productive one has not been directly addressed before. To clearly distinguish between these two possibilities, a system is needed in which one might detect allele‐specific germ‐line transcripts. We used homologous recombination to set up twoin vivo systems in which one γ3 allele was marked by a loxP sequence whereas the other allele was silenced by inhibiting μ heavy chain production. Here, we provide evidence that germ‐line transcription occurs on both the functional and the non‐functional alleles.
Pattern recognition receptors and differentiation antigens define murine myeloid cell heterogeneity ex vivo
Authors: Taylor Philip R. , Brown Gordon D. , Geldhof Anja B. , Martinez‐Pomares Luisa , Gordon Siamon
Published: July 2003

Recruitment of myeloid cells during inflammatory reactions plays an important role in the propagation and resolution of inflammation. However, the identification and characterization of these cells in mice has been hampered by cellular heterogeneity at the functional and phenotypic level. We have defined criteria for the rapid flow‐cytometric identification of monocytes (Mo), macrophages (MΦ), neutrophils (Neu) and eosinophils (Eos) in murine tissues using novel and established myeloid markers. These criteria were applied to the study of naive mice and mice with experimentally induced inflammation, both local and systemic, and also to a murine model of tumor progression. We show that the murine 7/4 antigen and the β‐glucan receptor, Dectin‐1, are particularly useful for the sub‐division of myeloid cells into individual populations, even when inflammatory conditions modulate their surface expression. Furthermore, 7/4 expression allows distinction between Mo recently recruited to a site and the resident cells already present. These studies highlight the heterogeneity of the murine Mo/MΦ‐lineage, define an extended phenotype for murine myeloid cells and greatly facilitate the ex vivo characterization of these cells during very different models of inflammation.
Mini‐review Activation‐induced cytidine deaminase: a dual role in class‐switch recombination and somatic hypermutation
Authors: Durandy Anne
Published: July 2003

Maturation of the antibody repertoire is mediated by two different mechanisms: class‐switch recombination (CSR) and somatic hypermutation (SHM). These two processes are T cell dependent and occur in the germinal centers of secondary lymphoid organs. CSR leads to the production of antibodies of different isotypes whereas SHM leads to the selection of B cells expressing a BCR with high affinity for antigen. The activation‐induced cytidine deaminase (AID) was recently shown to play a key role in these two mechanisms, demonstrating for the first time that these maturation processes share a common mechanism. There is evidence that AID is involved in the somatic DNA alterations required for CSR and SHM. The mechanism of action of AID is unclear. As AID and APOBEC‐1 display a sequence similarity, AID may act as an RNA‐editing enzyme. However, the immunological abnormalities observed in uracil‐N glycosylase deficiency in a recent study indirectly suggest that AID may edit DNA directly.
Allosteric Manipulation of Photoexcited State Relaxation in a Series of RuII(bpy)2(bipyridine−crown ethers)
Authors: Dutta Subodh K. , Gan Daqing , Perkovic Marc W.
Published: July 2003

A series of ruthenium(II) crown ether complexes containing 4‐, 5‐, or 6‐oxygen crowns tethered to a bipyridine at the 3,3′ position were prepared and examined for their ability to act as luminescent sensors. The complexes [(bpy)2Ru(2,2′‐bipyridine‐3,3′‐16‐crown‐4)](PF6)2 and [(bpy)2Ru(2,2′‐bipyridine‐3,3′‐19‐crown‐5)](PF6)2 were characterized by X‐ray crystallography. The 4‐oxygen crown crystallizes in the P$\bar 1$
space group. The 5‐oxygen crown crystallizes in the P$\bar 1$
space group. In both complexes, the inter‐pyridine ring angle in the tethered bipyridine is twisted substantially away from 0°. Coordination of a heavy metal ion such as Pb2+ by the crown ether, and the geometric changes that result, were examined by UV/Vis, luminescence and NMR spectroscopy. The results show that there is a weak allosteric interaction between the Pb2+ ion and the Ru complexes, and that this interaction alters the luminescent behavior of the Ru complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Chiral [(Dialkylamino)methyl](phospholyl)ferrocene Ligands as a New Class of 1,2‐Disubstituted Ferrocene Ligands
Authors: Mourgues Sophie , Serra Daniel , Lamy Franck , Vincendeau Sandrine , Daran Jean‐Claude , Manoury Eric , Gouygou Maryse
Published: July 2003

An efficient synthesis of new chiral [(dialkylamino)methyl](phospholyl)ferrocenes in an enantiomerically pure form has been developed. These new chiral N,P ligands have been tested in the palladium‐catalyzed allylic substitution reaction. High activities and moderate enantioselectivities (up to 67% ee) were observed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
P‐Modular Homochiral Bis(phosphanes) with 1,2‐Disubstituted Cyclopentane Backbones in Asymmetric Hydrogenation
Authors: Dahlenburg Lutz
Published: July 2003

The review surveys synthetic aspects of a class of bidentate phosphanes based on the trans‐1,2‐disubstituted cyclopentane framework and the application of such ligands in transition‐metal‐catalyzed enantioselective hydrogenation. In particular, we address the preparative potential of the isomerically pure multi‐purpose P−H and P−Cl reagents (R,R)‐ and (S,S)‐C5H8(PX2)2 (X = H, Cl), which can serve to construct a family of optically active bis(phosphanes) with structural components (“modules”) that are easily and systematically interchanged. The so‐designed chelate ligands allow access to rhodium catalysts with stereodiscriminating properties, depending on parameters such as (i) presence of P‐substituents that are equal or pairwise different in steric demand, (ii) spatial orientation of such substituents as defined by the endo‐ and exo‐chelate P−C−C−P and P−Rh−P−C torsion angles, and (iii) existence of C‐ and P‐chirogenic stereoelements in matched (or mismatched) combination. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis, Crystal and Magnetic Structure of the Double Perovskites A2NiMoO6 (A = Sr, Ba): A Neutron Diffraction Study
Authors: Martínez‐Lope María J. , Alonso José A. , Casais María T.
Published: July 2003

A2NiMoO6 (A = Sr, Ba) perovskites have been prepared in polycrystalline form by thermal treatment, in air, of previously decomposed citrate precursors. These materials have been studied by X‐ray (XRD) and neutron powder diffraction (NPD) data. At room temperature, the crystal structure is tetragonal, space group I4/m, for Sr2NiMoO6 and for Ba2NiMoO6 the crystal structure is cubic, space group Fm$\bar 3$
m. Both perovskites contain divalent Ni cations. The low temperature antiferromagnetic ordering has been followed from sequential neutron diffraction data. Peaks of magnetic origin appear in the NPD patterns below temperatures of TN = 81.2 K and TN = 64.3 K for the Sr and Ba compounds, respectively. The magnetic structures are defined by a propagation vector k = (1/2,0,1/2) for Sr2NiMoO6 and k = (1/2,1/2,1/2) for Ba2NiMoO6. The refined magnitude of the Ni magnetic moments also suggests a divalent oxidation state with S = 1. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Great Framework Variation of Polymers in the Manganese(II) Maleate/α,α′‐Diimine System: Syntheses, Structures, and Magneto‐Structural Correlation
Authors: Ma Chengbing , Chen Changneng , Liu Qiutian , Chen Feng , Liao Daizheng , Li Licun , Sun Licheng
Published: July 2003

Three novel manganese(II) coordination polymers, [Mn (maleate)(phen)]n (1; phen = 1,10‐phenanthroline), [Mn(maleate)(phen)]n·nH2O (2), and [Mn(maleate)(bpy)]n (3; bpy = 2,2′‐bipyridine), have been synthesized by treatment of Mn2+ with maleic acid with participation of chelate diimine ligands, and have been identified by single‐crystal X‐ray diffraction to have either one‐dimensional (1D) zigzag chain structures (1 and 2) or a two‐dimensional (2D) sinuous layer structure (3). Each maleate dianion coordinates to three Mn centers, in different bridging modes (syn‐anti in 1 and 2, syn‐syn and anti‐anti in 3). These compounds represent an interesting example of structural topology variation from 1D to 2D mediated by chemically similar auxiliary chelate ligands. Variable‐temperature magnetic susceptibility measurements show weak anti‐ferromagnetic exchange interactions between the adjacent MnII ions, with J = −0.06 cm−1 (2) and J = −1.3 cm−1, zJ′ = −0.27 cm−1 (3). The differences in the magnitudes of these coupling interactions agree well with the nature of the carboxylate‐bridging coordination of maleate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Lindqvist‐Type (Aryldiazenido)polyoxomolybdates − Synthesis, and Structural and Spectroscopic Characterization of Compounds of the Type (nBu4N)3[Mo6O18(N2Ar)]
Authors: Bustos Carlos , Hasenknopf Bernold , Thouvenot René , Vaissermann Jacqueline , Proust Anna , Gouzerh Pierre
Published: July 2003

A series of aryldiazenido compounds of the type (nBu4N)3[Mo6O18(N2Ar)] have been prepared by treatment of (nBu4N)4[Mo8O26] with the appropriate arylhydrazines in acetonitrile or in methanol. All these compounds are isostructural. Two members of the series, the o‐nitro and the p‐carboxy derivatives, have been characterized by single‐crystal X‐ray diffraction. The aryl ring in the first anion lies in a mirror plane of the polyoxometalate, while in the second one it is tilted, allowing hydrogen bonding between the carboxylic acid function and a neighbouring anion. The aryldiazenido ligands exhibit the characteristic features of the singly bent coordination mode with short Mo−N and N−N bond lengths indicative of multiple bond character. The compounds have been characterized by 95Mo and 17O NMR spectroscopy in acetonitrile. Their spectra indicate C4v symmetry, and hence stereochemical nonrigidity in solution. The 95Mo chemical shifts are mainly determined by variation in the paramagnetic shielding term, σpara. The strongly deshielded resonance of the MoII centre spans a large range (600−1100 ppm). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Electrodeposition of Lead at Boron‐Doped Diamond Film Electrodes: Effect of Temperature
Authors: Prado César , Wilkins Shelley J. , Gründler Peter , Marken Frank , Compton Richard G.
Published: July 2003

The electrodeposition of lead on boron‐doped diamond has been studied with a view to identifying the fundamental parameters controlling the sensitivity and lower detection limit in anodic stripping voltammetry. Chronoamperometric transients are used to explore the deposition, indicating a progressive growth mechanism confirmed by ex situ AFM images. Linear sweep ASV experiments show a threshold concentration of ca 10−6 M below which no lead is detected; this is attributed to the need for nucleation of the solid phase on the electrode. Experiments with variable temperature show that this threshold can be usefully lowered at elevated temperatures.
A Cholesterol Biosensor Based on Entrapment of Cholesterol Oxidase in a Silicic Sol‐Gel Matrix at a Prussian Blue Modified Electrode
Authors: Li Jianping , Peng Tuzhi , Peng Yuqiang
Published: July 2003

A cholesterol biosensors fabricated by immobilization of cholesterol oxidase (ChOx) in a layer of silicic sol‐gel matrix on the top of a Prussian Blue‐modified glassy carbon electrode was prepared. It is based on the detection of hydrogen peroxide produced by ChOx at −0.05 V. The half‐lifetime of the biosensor is about 35 days. Cholesterol can be determined in the concentration range of 1×10−6−8×10−5 mol/L with a detection limit of 1.2×10−7 mol/L. Normal interfering compounds, such as ascorbic acid and uric acid do not affect the determination. The high sensitivity and outstanding selectivity are attributed to the Prussian Blue film modified on the sensor.
The Current Usage of Selectivity Coefficients for the Characterization of Ion‐Selective Electrodes. A Critical Survey of the 2000/2001 Literature
Authors: Maccà Carlo
Published: July 2003

The articles describing new ion‐selective electrodes published during the years 2000/2001 in eight leading analytical chemistry journals have been surveyed. Compliance with the IUPAC recommendations of the procedures used for characterizing the selectivity of the new electrodes has been checked. It was found that the information accompanying the selectivity data obtained according to the procedures recommended by IUPAC or their variations was frequently insufficient for interpreting of the electrode behavior and comparing with other sets of data, thus reducing the significance of the values provided. Some criteria for improving the communication between researchers in the field are suggested.
A single‐strand conformation polymorphism method by capillary electrophoresis with laser‐induced fluorescence for detection of the T1151A mutation in hMLH1 gene
Authors: Shi Xianzhe , Xu Guowang , Zhao Chunxia , Ma Jianmei , Zhang Yan , Lv Shen , Yang Qing
Published: July 2003

Mutation of hMLH1 gene plays an important role in human tumorigenesis. A highly sensitive single‐strand conformation polymorphism (SSCP) method for detection of the T1151A mutation in exon 12 of the hMLH1 gene was for the first time developed employing laser‐induced fluorescence capillary electrophoresis (LIF‐CE). Effects of the concentration of linear polyacrylamide solution, running temperature, running voltage and the addition of glycerol on SSCP analysis were investigated, and the optimum separation conditions were defined. Thirty colorectal cancer patients and eight lung cancer patients were screened and the T1151A mutation was found in four of them. Based on CE‐sequencing the mutation was further confirmed. To our knowledge, this is for the first time that the T1151A mutation is found in lung cancer. Our method is simple, rapid, and highly sensitive and is well suited to the analysis of large numbers of clinical samples.
Two problematic human polymorphic Alu insertions
Authors: Luis Javier R. , Terreros Maria C. , Martinez Laisel , Rojas Dina , Herrera Rene J.
Published: July 2003

Analysis of two previously described polymorphic Alu insertions (Sb19.3 and NBC3) in world‐wide human populations generated genotypic frequencies grossly in violation of Hardy‐Weinberg equilibrium expectations. GenBank searches at the National Center for Biotechnology Information (NCBI) and sequencing analyses revealed that samples homozygous for the Sb19.3 Alu insertion amplify a band indistinguishable in size to the lack of insertion amplicon, corresponding to a paralogous locus on chromosome 4. This locus displays a very similar sequence (84%) to that flanking the Sb19.3 Alu insertion located at chromosome 19. Moreover, we have determined that NBC3, a different Alu insertion, is not located in the pseudoautosomal region of the Y‐chromosome, as previously reported, but in position Yq11.2. Also, the band that mimics the lack of insertion amplicon corresponds to a paralogous locus located at chromosome X with a similarity of 92% to the sequence flanking the NBC3 Alu insertion. Finally, the utilization of newly designed primers avoided amplification from the paralogous loci and allowed a reliable assignation of genotypes for both loci. Unlike previously reported, using our new primers the Y‐specific locus NBC3 was found not to be polymorphic in the populations analyzed.