bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of physicochemical reactions of bioactive glass on the behavior and activity of human osteoblasts in vitro
Authors: Josset Y. , Nasrallah F. , Jallot E. , Lorenzato M. , Dufour‐Mallet O. , Balossier G. , Laurent‐Maquin D.
Published: November 2003

Bioactive glasses are characterized by a bond to bone with a hydroxyl carbonate apatite layer. They enhance bone tissue formation and for this purpose are used in orthopedic surgery and in dental implantology. In the current work, we studied the biological response of human osteoblasts with a bioactive glass. This bioactive glass is based on 50% Si02, 20% Na2O, 16% CaO, 6% P2O5, 5% K20, 2% Al2O3 and 1% MgO and designated A9. Cracks and irregularities were observed on the material surface when it was immersed in the culture medium. In addition, energy dispersive X‐ray analyses highlighted a selective release of the elements at the surface of the bioactive glass, such as Na+ and K+ ions, released from the first day, contrary to the Si, Al, Ca, P, and Mg elements, which were released more slowly. Cell proliferation kinetics, total protein synthesis, and DNA content of the osteoblasts in contact with bioactive glass were similar to control cells. The morphological studies by light and scanning electron microscopy revealed an increasing cellular density in culture with bioactive glass without contact inhibition. The immunohistochemical studies highlighted the expression of types I, III, and V collagens by osteoblasts cultured in the presence of bioactive glass. The pH measurement of the culture medium in the presence of bioactive glass demonstrated a slight alkalinization. We thus conclude that human osteoblasts preserve their properties in the presence of bioactive glass (A9). © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1205–1218, 2003
Surface potential change in bioactive titanium metal during the process of apatite formation in simulated body fluid
Authors: Kim Hyun‐Min , Himeno Teruyuki , Kawashita Masakazu , Lee Ju‐Hyung , Kokubo Tadashi , Nakamura Takashi
Published: November 2003

Bioactive titanium metal can be prepared by NaOH and heat treatments that present the metal with a graded bioactive surface layer of amorphous sodium titanate. This study used laser electrophoresis together with transmission electron microscopy (TEM) and energy‐dispersive X‐ray microanalysis (EDX) to relate the surface potential change of the bioactive titanium metal with its surface structural change in simulated body fluid (SBF). The surface potential of the metal was highly negative immediately after immersion in SBF. With increasing soaking time, the surface potential increased, revealing a maximum positive value, and then decreased to a constant negative value. TEM‐EDX showed that immediately after immersion in SBF, the metal surface formed Ti‐OH groups by exchanging Na+ ions in the surface sodium titanate with H3O+ ions in the fluid. Thereafter, with increasing soaking time the metal surface formed an amorphous calcium titanate, then an amorphous calcium phosphate, and, finally, apatite with bone‐like composition and structure. These results indicate that the process of apatite formation on bioactive titanium metal is initiated by the formation of Ti‐OH groups with negative charges that interact with calcium ions with positive charges to form calcium titanate. The calcium titanate gains a positive charge and later interacts with phosphate ions with negative charges, forming amorphous calcium phosphate. The amorphous calcium phosphate eventually transforms and stabilizes into bone‐like crystalline apatite with a negative charge. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1305–1309, 2003
Biodegradable poly(ether‐ester) multiblock copolymers for controlled release applications
Authors: van Dijkhuizen‐Radersma R. , Roosma J.R. , Kaim P. , Métairie S. , Péters F.L.A.M.A. , de Wijn J. , Zijlstra P.G. , de Groot K. , Bezemer J.M.
Published: November 2003

Multiblock poly(ether‐ester)s based on poly(ethylene glycol), butylene terephthalate, and butylene succinate units were synthesized by a two‐step melt polycondensation reaction, with the aim of developing a new series of degradable polymers for controlled release applications. The copolymers were characterized with respect to their composition (NMR), thermal properties (DSC), and swelling. The main focus was on the degradation kinetics and release properties of the copolymers. The crystallinity and swelling could be tailored by the PEG segment length and the ratio of the building units. With increasing mol fraction succinate in the hard segment, the swelling increased. The in vitro degradation was found to occur by molecular weight decrease and mass loss. Substitution of the aromatic terephthalate units by aliphatic succinate units increased the degradation rate of the copolymers. Polymers with PEG segments of 1000 kg/mol showed a more pronounced degradation than copolymers containing shorter and longer PEG segments. Model proteins were successfully incorporated and released from the poly(ether‐ester) films. Depending on the size of the protein, the release mechanism was based on diffusion of the protein and degradation of the matrix. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1294–1304, 2003
Differential gene expression analysis using paraffin‐embedded tissues after laser microdissection
Authors: Kim Joung‐Ok , Kim Hyun‐Nam , Hwang Mi‐Hye , Shin Hong‐In , Kim Shin‐Yoon , Park Rang‐Woon , Park Eui‐Yun , Kim In‐San , van Wijnen Andre J. , Stein Janet L. , Lian Jane B. , Stein Gary S. , Choi Je‐Yong
Published: November 2003

Recent advances in laser microdissection allow for precise removal of pure cell populations from morphologically preserved tissue sections. However, RNA from paraffin‐embedded samples is usually degraded during microdissection. The purpose of this study is to determine the optimal fixative for RNA extractions from laser microdissected paraffin‐embedded samples. The integrity of RNA was evaluated with the intactness of 18S and 28S ribosomal RNA by electrophoresis and by the length of individual gene transcripts using RT‐PCR. The various fixatives were methacarn (a combination of methanol, chloroform, and acetic acid) and several concentrations of ethanol and isopropanol. Methacarn was the optimal fixative for RNA preservation in paraffin‐embedded tissues, which included liver, lung, kidney, muscle, and limb. Based on RT‐PCR analysis, methacarn fixed samples exhibited the expected RNA sizes for individual genes such as glyceraldehyde‐3‐phosphate‐dehydrogenase (GAPDH) and bone‐related genes (e.g., alkaline phosphatase and osteonectin). The laser microdissection technique with methacarn fixation was then applied to analyze the differential gene expression between hypertrophic and proliferative chondrocytes in the growth plate of long bone. The expression of type X collagen (ColXα1), a specific gene for hypertrophic chondrocytes, was only observed in hypertrophic chondrocytes, while type II collagen (Col2α1) was observed more broadly in the growth plate as anticipated. Thus, combining laser microdissection with methacarn fixation facilitates the examination of differentially expressed genes from various tissues. © 2003 Wiley‐Liss, Inc.
β‐phenylpyruvate and glucose uptake in isolated mouse soleus muscle and cultured C2C12 muscle cells
Authors: Ben‐Abraham Ron , Gazit Vered , Vofsi Oded , Ben‐Shlomo Izahar , Reznick Abraham Z. , Katz Yeshayahu
Published: November 2003

Previous investigation demonstrated the potential of β‐phenylpyruvate at high concentration to cause hypoglycemia in mice totally deprived of insulin. For further elucidation of the glucose‐lowering mechanism, glucose uptake, and quantity of glucose transporters (GLUT1 and GLUT4) in mouse soleus muscle and C2C12 muscle cell lines were investigated following incubation with β‐phenylpyruvate in various concentrations. A marked enhancement of glucose uptake was demonstrated that peaked at 0.5 and 1.0 mM β‐phenylpyruvate in soleus muscle (P < 0.01) and C2C12 cells (P < 0.001), respectively. Kinetic analysis in C2C12 cells showed a twofold increase in Vmax compared with controls (P < 0.001). In addition, both GLUT1 and GLUT4 levels were increased following exposure to β‐phenylpyruvate. Our findings point to a peripheral hypoglycemic effect of β‐phenylpyruvate. © 2003 Wiley‐Liss, Inc.
Identification of a novel protein from glial cells based on its ability to interact with NF‐κB subunitsr
Authors: Sweet Thersa , Khalili Kamel , Sawaya Bassel E. , Amini Shohreh
Published: November 2003

Nuclear factor κB (NF‐κB) represents a family of inducible DNA‐binding transcription factors whose activity is critical for expression of the HIV‐1 genome in a broad range of cells. In addition to its interaction with the κB DNA sequence, the association of NF‐κB subunits with other cellular proteins plays an important role in stimulation of HIV‐1 gene transcription in astrocytic cells. Here, we utilized a yeast two‐hybrid system to screen a cDNA library from a human astrocytic cell line and were able to isolate a partial cDNA belonging to a gene with an open reading frame of 1,871 amino acid residues which binds to both the p50 and p65 subunits of NF‐κB. This gene, named NF‐κB‐binding protein (NFBP) is located on chromosome 10q24.2‐25.1 and hybridized to a single transcript of nearly 6 kb in size. It is localized to the nucleus, specifically the nucleolus of cells. Extensive computer analysis was performed with the sequence of the full length NFBP and significant homology was found between NFBP, and yeast and mouse proteins. A discussion of the potential roles of NFBP in normal and viral infected cells is included. © 2003 Wiley‐Liss, Inc.
SHP‐1 suppresses cancer cell growth by promoting degradation of JAK kinases
Authors: Wu Chengyu , Guan Qin , Wang Yingjian , Zhao Z. Joe , Zhou G. Wayne
Published: November 2003

SHP‐1 has been proposed to be a tumor suppressor gene for several cancers. The expression of SHP‐1 protein is diminished or abolished in most leukemia and lymphoma cell lines and tissues, and in some non‐hematopoietic cancer cell lines, such as estrogen receptor (ER) negative breast cancer cell lines and some colorectal cancer cell lines. However, we do not know whether the reduced SHP‐1 expression is the cause of cancer diseases or the secondary effect of cancer developments. Here, we first demonstrate that SHP‐1 has general tumor suppressing function in SHP‐1 transfected cell lines. Transfected SHP‐1 inhibits the growth of three lymphoma/leukemia cell lines (Ramos, H9, Jurkat) and one breast cancer cell line (HTB26). We also demonstrate a possible molecular mechanism for the tumor suppressing function of SHP‐1: SHP‐1 inhibits cell growth partly by negative regulation of activated JAK kinase. In addition, we find, for the first time, that SHP‐1 down‐regulates the level of TYK2 kinase in H9 cells and of JAK1 kinase in HTB26 cells, by accelerating their degradation. The SHP‐1 accelerated degradation of JAK1 kinase in HTB26 cells was blocked with the treatment of MG132, a specific inhibitor for proteasome‐mediated proteolysis. Our data suggest a new function of SHP‐1 in the regulation of proteasome‐mediated degradation pathway. © 2003 Wiley‐Liss, Inc.
Transcriptional regulation of collagenase‐3 by interleukin‐1 alpha in osteoblasts
Authors: Varghese Samuel , Canalis Ernesto
Published: November 2003

Interleukin‐1 (IL‐1)α is an autocrine/paracrine agent of the skeletal tissue and it regulates bone remodeling. Collagenase‐3 or matrix metalloproteinase (MMP)‐13 is expressed in osteoblasts and its expression is modulated by several cytokines including IL‐1α. Because the molecular mechanism of increased synthesis of collagenase‐3 in bone cells by IL‐1α is not known, we investigated if collagenase‐3 expression by IL‐1α in osteoblasts is mediated by transcriptional or post‐transcriptional mechanisms. Exposure of rat osteoblastic cultures (Ob cells) to IL‐1α at concentrations higher than 0.5 nM increased the synthesis of collagenase‐3 mRNA up to eightfold and the secretion of immunoreactive protein up to 21‐fold. The effects of IL‐1α on collagenase‐3 were time‐ and dose‐dependent. Although prostaglandins stimulate collagenase‐3 expression, stimulation of collagenase‐3 in Ob cells by IL‐1α was not mediated through increased biosynthesis of prostaglandins. The half‐life of collagenase‐3 mRNA from control and IL‐1α‐treated Ob cells was similar suggesting that the stabilization of collagenase‐3 mRNA did not contribute to the increase in collagenase‐3. However, IL‐1α stimulated the rate of transcription of the collagenase‐3 gene by twofold to fourfold indicating regulation of collagenase‐3 expression in Ob cells at the transcriptional level. Stimulation of collagenase‐3 by IL‐1α in osteoblasts may in part mediate the effects of IL‐1α in bone metabolism. © 2003 Wiley‐Liss, Inc.
Performance of PML absorbing boundary conditions in 3D photonic crystal waveguides
Authors: Weily Andrew R. , Horvath Levente , Esselle Karu P. , Sanders Barry C.
Published: November 2003

We present a numerical analysis of the performance of three‐dimensional (3D) perfectly matched layer (PML) absorbing boundary conditions (ABCs) in a photonic crystal (PC) waveguide. This formulation dramatically reduces the reflections from the ends of the PC waveguide, leading to highly accurate transmittance and reflectance calculations for waveguide components. The 3D PC‐based PML ABC is demonstrated to give good results when used to analyze a 90° bend in a 3D PC waveguide. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 1–3, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11268
Low‐loss microwave filters on CMOS‐grade standard silicon substrate with low‐k BCB dielectric
Authors: Leung Lydia L. W. , Chen Kevin J. , Huo Xiao , Chan Philip C. H.
Published: November 2003

Benzocyclobutene (BCB), a low‐k, photosensitive, easily patterned material is used as the interfacing layer that isolates the passive components from the lossy, low‐resistivity silicon. Its performance is further improved by reducing the conductive loss with an electroplated and highly‐conductive metal, namely, copper. Standard 50‐Ω microstrip lines and a microstrip‐transmission‐line‐based microwave filter, exhibiting insertion losses of 0.8 dB and 1.1 dB at 10 GHz, respectively, are demonstrated. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 9–11, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11271
Modelling approaches to compare sorption and degradation of metsulfuron‐methyl in laboratory micro‐lysimeter and batch experiments
Authors: Heistermann Maik , Jene Bernhard , Fent Gunnar , Feyerabend Martin , Seppelt Ralf , Richter Otto , Kubiak Roland
Published: November 2003

Results of laboratory batch studies often differ from those of outdoor lysimeter or field plot experiments—with respect to degradation as well as sorption. Laboratory micro‐lysimeters are a useful device for closing the gap between laboratory and field by both including relevant transport processes in undisturbed soil columns and allowing controlled boundary conditions. In this study, sorption and degradation of the herbicide metsulfuron‐methyl in a loamy silt soil were investigated by applying inverse modelling techniques to data sets from different experimental approaches under laboratory conditions at a temperature of 10 °C: first, batch‐degradation studies and, second, column experiments with undisturbed soil cores (28 cm length × 21 cm diameter). The column experiments included leachate and soil profile analysis at two different run times. A sequential extraction method was applied in both study parts in order to determine different binding states of the test item within the soil. Data were modelled using ModelMaker and Hydrus‐1D/2D.

Metsulfuron‐methyl half‐life in the batch‐experiments (t1/2 = 66 days) was shown to be about four times higher than in the micro‐lysimeter studies (t1/2 about 17 days). Kinetic sorption was found to be a significant process both in batch and column experiments. Applying the one‐rate‐two‐site kinetic sorption model to the sequential extraction data, it was possible to associate the stronger bonded fraction of metsulfuron‐methyl with its kinetically sorbed fraction in the model. Although the columns exhibited strong significance of multi‐domain flow (soil heterogeneity), the comparison between bromide and metsulfuron‐methyl leaching and profile data showed clear evidence for kinetic sorption effects. The use of soil profile data had significant impact on parameter estimates concerning sorption and degradation. The simulated leaching of metsulfuron‐methyl as it resulted from parameter estimation was shown to decrease when soil profile data were considered in the parameter estimation procedure. Moreover, it was shown that the significance of kinetic sorption can only be demonstrated by the additional use of soil profile data in parameter estimation. Thus, the exclusive use of efflux data from leaching experiments at any scale can lead to fundamental misunderstandings of the underlying processes. Copyright © 2003 Society of Chemical Industry
Extra large particle images at 12 km in a hurricane eyewall: Evidence of high‐altitude supercooled water?
Authors: Black Robert A. , Heymsfield Gerald M. , Hallett John
Published: November 2003

The conventional wisdom about hurricanes suggests that updrafts are weak and supercooled water is scarce in the eyewall, and almost non‐existent at temperatures colder than about −5°C [Black and Hallett, 1986]. However, there is evidence that some hurricanes are different. Questions about the existence of high‐altitude supercooled cloud water cannot be answered with only the instruments aboard the typical propeller‐driven aircraft. During the summer of 1998, the NASA DC‐8 aircraft made penetrations of the intensifying eyewall of Hurricane Bonnie at 12 km MSL, collecting the first truly high‐altitude 2‐D particle imagery in a hurricane. The similarity of the splash images in Hurricane Bonnie to those from raindrops obtained at higher temperatures in other hurricanes suggests that the large images obtained by the DC‐8 were soft, low density graupel, rather than hard, high‐density graupel particles or frozen raindrops. This implies that these particles grew to several millimeters in diameter at altitude, rather than simply advecting from lower, warmer altitudes. This growth in turn requires the presence of deeply supercooled cloud droplets. Thermal emission from supercooled water aloft increases the microwave brightness temperatures, giving a misleading impression that there is much less ice aloft than actually exists. The extra attenuation from the occasional presence of large graupel at these altitudes reduces the ability of microwave sensors to see precipitation at lower altitudes. Both of these effects impede efforts to accurately quantify condensate mass remotely from radiometric data such as that provided by the TRMM satellite.
The occurrence and chemical implications of geothermal convection of seawater in continental shelves
Authors: Wilson Alicia M.
Published: November 2003

Geothermal convection is an important driving force for fluid flow and diagenesis in carbonate platforms, and the similar shape of continental shelves in general suggests that geothermal convection could occur in continental shelves around the world. Numerical models based on seven transects of the shelf off the east coast of North America were developed to bracket possible fluxes. Simulations assuming relatively permeable sediments (medium‐grained carbonates) failed to produce significant thermal variations, suggesting that chemical tracers will be required to detect this flow in the field. Fluxes calculated assuming lower permeabilities (fine grained carbonates) between Cape Fear and the Savannah River were approximately 3 orders of magnitude smaller than river discharge for the area, a difference similar to that between global river discharge and hydrothermal convection at mid‐ocean ridges. Sediment diagenesis during geothermal convection in continental shelves thus has the potential to affect ocean chemical budgets, including potassium, calcium, and magnesium.
Near‐source and remote observations of kilometric continuum radiation from multispacecraft observations
Authors: Menietti J. D. , Anderson R. R. , Pickett J. S. , Gurnett D. A. , Matsumoto H.
Published: November 2003

Kilometric continuum (KC) radiation was first identified from Geotail plasma wave observations. Past authors have shown that this emission has a frequency range that overlaps that of the auroral kilometric radiation (AKR) but is characterized by a fine structure of narrow‐bandwidth, linear features that have nearly constant or drifting frequency. This fine structure is distinct from that of AKR. KC also apparently has a distinct source region probably associated with the low‐latitude inner magnetosphere, consistent with direction‐finding and ray‐tracing results. We present new high‐resolution electric and magnetic field observations of KC obtained by the Polar plasma wave instrument in the near‐source region. These observations show intense electrostatic and less intense electromagnetic emissions near the magnetic equator at the plasmapause. Simultaneously, Geotail, located at 20 to 30 RE in radial distance, observes KC in the same frequency range. These data support a possible mode‐conversion source mechanism near a region of high‐density gradient. High‐resolution data obtained from wideband receivers on board both Polar and Cluster show closely spaced bands of emission near the magnetic equator that may be due to many nearby independent sources of EM emission perhaps associated with density fluctuations or cavities in the plasmasphere.
Intercontinental transport of pollution manifested in the variability and seasonal trend of springtime O3 at northern middle and high latitudes
Authors: Wang Yuhang , Shim Changsub , Blake Nicola , Blake Donald , Choi Yunsoo , Ridley Brian , Dibb Jack , Wimmers Anthony , Moody Jennie , Flocke Frank , Weinheimer Andrew , Talbot Robert , Atlas Elliot
Published: November 2003

Observations (0–8 km) from the Tropospheric Ozone Production about the Spring Equinox (TOPSE) experiment are analyzed to examine air masses contributing to the observed variability of springtime O3 and its seasonal increase at 40°–85°N over North America. Factor analysis using the positive matrix factorization and principal component analysis methods is applied to the data set with 14 chemical tracers (O3, NOy, PAN, CO, CH4, C2H2, C3H8, CH3Cl, CH3Br, C2Cl4, CFC‐11, HCFC‐141B, Halon‐1211, and 7Be) and one dynamic tracer (potential temperature). Our analysis results are biased by the measurements at 5–8 km (70% of the data) due to the availability of 7Be measurements. The identified tracer characteristics for seven factors are generally consistent with the geographical origins derived from their 10 day back trajectories. Stratospherically influenced air accounts for 14 ppbv (35–40%) of the observed O3 variability for data with O3 concentrations <100 ppbv at middle and high latitudes. It accounts for about 2.5 ppbv/month (40%) of the seasonal O3 trend at midlatitudes but for only 0.8 ppbv/month (<20%) at high latitudes, likely reflecting more vigorous midlatitude dynamical systems in spring. At midlatitudes, reactive nitrogen‐rich air masses transported through Asia are much more significant (11 ppbv in variability and 3.5 ppbv/month in trend) than other tropospheric contributors. At high latitudes the O3 variability is significantly influenced by air masses transported from lower latitudes (11 ppbv), which are poor in reactive nitrogen. The O3 trend, in contrast, is largely defined by air masses rich in reactive nitrogen transported through Asia and Europe across the Pacific or the Arctic (3 ppbv/month). The influence from the stratospheric source is more apparent at 6–8 km, while the effect of O3 production and transport within the troposphere is more apparent at lower altitudes. The overall effect of tropospheric photochemical production, through long‐range transport, on the observed O3 variability and its seasonal trend is more important at high latitudes relative to more photochemically active midlatitudes.
A semiannual variation of ozone in the middle mesosphere observed with the millimeter‐wave radiometer at Tsukuba, Japan
Authors: Nagahama Tomoo , Nakane Hideaki , Fujinuma Yasumi , Ogawa Hideo , Mizuno Akira , Fukui Yasuo
Published: November 2003

Continuous observations of the vertical ozone profiles between 38 and 76 km in altitude have been made with the millimeter‐wave radiometer at Tsukuba, Japan (36.1°N, 140.1°E) since October 1996. We analyzed temporal variations of ozone at various altitudes and first identified clearly the features of a semiannual variation between 56 and 68 km. The ozone mixing ratio in this region peaks in January and July, and the amplitude of the semiannual variation at 60 km was estimated to be 13% of the annual average, which is about half the value of 28% observed at 76 km. The phase of the semiannual variation from 56 to 76 km inverts suddenly at around 68 km, suggesting that these semiannual variations of ozone are not induced by the propagation of any kind of wave but are caused by different mechanisms in the regions above and below 68 km.
A Bayesian space‐time analysis of acid deposition data combined from two monitoring networks
Authors: Cowles Mary Kathryn , Zimmerman Dale L.
Published: November 2003

In some studies of atmospheric pollution, deposition data may be available from several distinct monitoring networks. Systematic differences may exist between networks, and an effective statistical analysis of the data combined from all networks should account for this possibility. This article develops a Bayesian modeling approach for spatiotemporal data from two monitoring networks that accounts for possible network differences in measurement error biases and variances. Wet sulfate deposition data from two networks in the eastern United States, the National Acid Deposition Program/National Trends Network and the Clean Air Status and Trends Network, are combined and analyzed via our modeling approach. We examine whether the temporal trend in deposition from 1989–1997 varies regionally and whether the measurement error biases and variances differ between networks. We also demonstrate how prediction uncertainty is reduced using the combined data from levels obtained when basing prediction on data from only one of the networks.
The Contemporary Presidency: The Twenty‐Fifth Amendment: Recommendations and Deliberations of the Working Group on Presidential Disability
Authors: Gilbert Robert E.
Published: November 2003

The Twenty‐fifth Amendment was added to the Constitution in 1967 as a response to long‐festering issues of presidential disability and succession. Jimmy Carter and other critics have argued, however, that the amendment is badly flawed. In response to Carter's suggestion, the Working Group on Presidential Disability was established in 1994 and, in late 1996, presented nine recommendations for strengthening the amendment to President Clinton at the White House. These are cited here and a number are explained and defended. Also, the suggestion made by some Working Group members that a Standing Medical Commission be created by law to monitor the president's health and issue periodic reports to the country is critiqued, using, in part, a case study derived from the presidency of John F. Kennedy.
Territorial behaviour and population dynamics in red grouse Lagopus lagopus scoticus. I. Population experiments
Authors: Mougeot François , Redpath Steve M. , Moss Robert , Matthiopoulos Jason , Hudson Peter J.
Published: November 2003

According to the ‘territorial behaviour’ hypothesis, population cycles of red grouse are caused by delayed density‐dependent changes in the aggressiveness of territorial cocks. We report here on a replicated population experiment testing assumptions of this hypothesis.

We used testosterone implants to increase aggressiveness of cocks for 3 months during autumn, when recruitment and territory establishment take place. On two moors located in northern England, and on two 1‐km2 areas within each moor, we implanted adult cocks with testosterone on an experimental area and with sham implants on a control area.

During the first autumn, the testosterone treatment prevented recruitment of young cocks into the territorial populations. This reduced breeding density and altered the age ratio among territorial cocks, and possibly levels of kinship. If so, the ‘kinship’ hypothesis predicted that density and recruitment should continue to differ between testosterone‐treated and control areas.

Grouse density remained significantly lower on the experimental than on the control areas for two consecutive breeding seasons. This confirmed a strong spatial structuring within grouse populations, which prevented immigration from neighbouring higher‐density areas. In the second autumn, testosterone was not implanted but the recruitment rate remained significantly lower and cock density continued to decline more on the experimental than on the control areas.

The results suggest that cocks continued to be aggressive and to maintain large territories for at least a year after aggressiveness was increased experimentally, and therefore that autumn aggressiveness is influenced by previous territorial contests.

The experiment validates key assumptions of the ‘territorial behaviour’ hypothesis for red grouse cycles. Population models in a subsequent paper demonstrate how changes in aggressiveness can cause population cycles.
Acquisition of desiccation tolerance in developing wheat embryos correlates with appearance of a fluid phase in membranes
Authors: GOLOVINA E. A. , HOEKSTRA F. A.
Published: November 2003

Membrane behaviour in developing wheat (Triticum aestivum cv Priokskaya) embryos was studied in relation to the acquisition of desiccation tolerance, using spin probe techniques. Fresh embryos were able to develop into seedlings at day 15 after anthesis, but it took 18 d before fast‐dried, isolated embryos could germinate. On the basis of membrane integrity measurements it was estimated that between 14 and 18 d after anthesis the proportion of embryonic cells surviving fast drying increased and the critical moisture content, to which embryonic cells could be dehydrated, decreased. Apparently, embryonic cells do not acquire the same level of desiccation tolerance simultaneously. Only when all cells had become desiccation tolerant was germination of air‐dried embryos possible. Using 5‐doxylstearic acid as the probe molecule, an approximately similar lipid–water interface ordering of membranes was observed in all hydrated embryos, irrespective of age. Dehydration had a dual effect on the lipid interface: further ordering of the major part of the interface and the appearance of additional, disturbed regions. The proportion of these regions correlated with the proportion of desiccation‐tolerant cells. We propose that the membrane surface disturbance be caused by endogenous amphiphiles that partition from the cytoplasm into membranes during drying. The absence of such disturbed regions in dried, desiccation‐sensitive embryos might reflect a lack of sufficient amphiphiles. The relevance of membrane surface disturbance for desiccation tolerance is discussed.
Large‐scale identification of leaf senescence‐associated genes
Authors: Gepstein Shimon , Sabehi Gazalah , Carp Marie‐Jeanne , Hajouj Taleb , Nesher Mizied Falah Orna , Yariv Inbal , Dor Chen , Bassani Michal
Published: November 2003

Leaf senescence is a form of programmed cell death, and is believed to involve preferential expression of a specific set of ‘senescence‐associated genes’ (SAGs). To decipher the molecular mechanisms and the predicted complex network of regulatory pathways involved in the senescence program, we have carried out a large‐scale gene identification study in a reference plant, Arabidopsis thaliana. Using suppression subtractive hybridization, we isolated approximately 800 cDNA clones representing SAGs expressed in senescing leaves. Differential expression was confirmed by Northern blot analysis for 130 non‐redundant genes. Over 70 of the identified genes have not previously been shown to participate in the senescence process. SAG‐encoded proteins are likely to participate in macromolecule degradation, detoxification of oxidative metabolites, induction of defense mechanisms, and signaling and regulatory events. Temporal expression profiles of selected genes displayed several distinct patterns, from expression at a very early stage, to the terminal phase of the senescence syndrome. Expression of some of the novel SAGs, in response to age, leaf detachment, darkness, and ethylene and cytokinin treatment was compared. The large repertoire of SAGs identified here provides global insights about regulatory, biochemical and cellular events occurring during leaf senescence.
The cost of allogeneic red blood cells – a systematic review
Authors: Amin M. , Fergusson D. , Aziz A. , Wilson K. , Coyle D. , Hébert P.
Published: November 2003

Summary.  Several reports suggest that the cost of RBCs may have risen over time, but there exists very little published evidence of that. The objective was to determine whether published studies documenting cost data on RBCs suggest an increase over time and to assess the quality of cost studies. We used the terms ‘cost’, ‘allogeneic/allogenic’ and ‘blood’ to identify cost studies between 1966 and 2002 from Medline, ISIesource and Ingenta electronic databases. Furthermore, we manually searched a number of transfusion and health economics journals for completeness. We included studies that used an established methodology and conducted an economic evaluation using primary/secondary cost data to calculate the cost of RBCs and RBC transfusion. Studies without allogeneic RBCs as comparator were excluded. Two individuals independently reviewed the studies and included studies upon reaching a consensus. Fourteen studies qualified the selection criteria and were included in the review. Ten studies were identified from Medline, two from Ingenta, one from ISIesource and one was a conference paper. Of the 14 studies reviewed, 10 had focused on RBC transfusion and four had focused on both RBCs and RBC transfusion. Ten studies were from the US, and two each from Canada and the UK, respectively. Two studies had explicit objective of cost calculation, and others had calculated costs towards fulfilling other objectives. Most of the reviewed studies were dated and of poor quality. Despite these limitations, it appears that the cost of RBCs has increased over time in the UK, Canada and the US. More studies are needed to fully assess the trend of costs over time. Future cost studies should try to follow the economic evaluation guidelines for greater research implications.
Autologous red cells derived from cord blood: collection, preparation, storage and quality controls with optimal additive storage medium (Sag‐mannitol)
Authors: Garritsen H. S. P. , Brune T. , Louwen F. , Wüllenweber J. , Ahlke C. , Cassens U. , Witteler R. , Sibrowski W.
Published: November 2003

Summary.  To investigate whether packed red cells (PRCs) prepared from autologous cord blood‐packed red cells (AC‐PRCs) could be used as an alternative for homologous‐packed red cells (H‐PRCs), we developed a system to collect and prepare AC‐PRCs and determined standard storage parameters during 35 days of storage in extended storage medium (Sag‐mannitol). We collected and fractionated cord blood from 390 newborns. The amount and quality of the AC‐PRCs were analysed. The bacterial contamination rate was 1·84%. Twelve AC‐PRCs were stored for 35 days, and standard laboratory parameters were measured at day 1 and day 35. The initial laboratory parameters of the AC‐PRCs were similar to the parameters of the H‐PRCs. After 35 days, the AC‐PRCs displayed an increased haemolysis rate compared to H‐PRCs (1·1 versus 0·2%) and also a significant decreased adenosine triphosphate value (1·2 versus 2·3 µmol L−1). Haemoglobin, haematocrit and pH were comparable in both groups. AC‐PRCs meet the quality criteria for H‐PRCs after 35 days. Utilizing a closed collection system for cord blood and an extended storage medium will increase safety and quality and facilitate the routine transfusion of autologous red cells derived from cord blood.
Peripheral eosinophilia and eosinophilic gastroenteritis after pediatric liver transplantation
Authors: Romero René , Abramowsky Carlos R. , Pillen Todd , Smallwood Gregory A. , Heffron Thomas G.
Published: November 2003

Abstract:  Reports indicate peripheral eosinophilia (PE) and gastrointestinal eosinophilic inflammation can occur after pediatric liver transplantation. The incidence of these conditions, potential risk factors, and the impact of PE and gastrointestinal eosinophilic inflammation on liver transplant outcome were determined in this pediatric liver transplant program. Medical records of liver transplant recipients from 1 to 97 and from 12 to 99 were reviewed. Fifty‐seven transplants on 54 patients were performed during the study period. Fifty‐three patients were evaluated; all had normal pre‐transplantation peripheral eosinophil counts. PE of >10% developed in 28% of patients. Using this definition, all such identified patients had absolute eosinophil counts of >350/mm3. History of immediate hypersensitivity did not differ between patients with or without eosinophilia. Gastrointestinal endoscopy and biopsy was performed in 23 patients with gastrointestinal complaints. Of those, six had eosinophilic gastroenteritis and all six had PE. Compared with patients without eosinophilia, those with PE were younger at the time of transplantation (p < 0.05), had more frequent rejection (p < 0.01), were more commonly managed with tacrolimus‐based immunosuppression (p < 0.001), and experienced more frequent episodes of detectable EBV viral load (p < 0.04). Patients with eosinophilic gastroenteritis were more frequently retransplanted (p < 0.006). PE associated with symptomatic eosinophilic gastroenteritis is common after pediatric liver transplantation. Age at transplant, frequency of rejection episodes, tacrolimus‐based immunosuppression, and EBV viral load may be associated with the development of this condition. There may be higher rates of graft loss in such patients. Whether innate immune responsiveness or an acquired immune dysregulation accounts for these findings merits further evaluation.
A typology of non‐adherence in pediatric renal transplant recipients
Authors: Shaw Richard J. , Palmer Laura , Blasey Christine , Sarwal Minnie
Published: November 2003

Abstract:  We reviewed 112 pediatric renal transplant recipients to document the rate of medication non‐adherence (NA) and to examine the relationships between NA, comorbid psychiatric illness, and the outcome variables of acute and chronic rejection and graft loss. A total of 32.5% of subjects had clinically significant NA with treatment based on review of serum immunosuppressant levels. NA was found to be significantly related to acute and chronic rejection, and graft loss (p < 0.001). NA was also related to the presence of comorbid psychiatric illness (p < 0.001). Logistic regression indicated that NA was a significant predictor for acute and chronic rejection, while psychiatric illness predicted graft loss. Adolescents had significantly higher rates of NA as well as shorter intervals between transplant date and onset of NA when compared with child patients (p < 0.001). Physician ratings of the primary reasons for NA suggested that lack of parental supervision and parent–child conflict were the major factors related to NA.
HLA‐B*5808, a new HLA‐B allele characterized by sequence based typing
Authors: Poli F. , Crespiatico L. , Frison S. , Longhi E. , Marlianici E. , Scalamogna M.
Published: November 2003

Abstract:  This brief communication describes a new HLA‐B allele (HLA‐B*5808) detected in an Italian white volunteer bone marrow donor. With serology, this subject was typed as HLA‐B15,17, whereas with molecular biology B*15, B*51, B*52 and/or B*58 could be assigned. In order to clarify the results, direct and cloning sequencing of exons 2, 3 and 4 were carried out. This new allele is identical to HLA‐B*5801 in exon 2 except for a silent point mutation at nucleotide 141 where a C is substituted by a T; exons 3 and 4 are typical of HLA‐B*51, B*52 and B*78. The peculiar sequence of B*5808 could explain the discrepancy between the serological and molecular typing results.
HLA diversity among Nadars, a primitive Dravidian caste of South India
Authors: Shankarkumar U. , Sridharan B. , Pitchappan R.M.
Published: November 2003

Abstract:  South India is one of the oldest geophysical regions mainly occupied by Dravidian language‐speaking people. Here a random panel of 61 unrelated Nadar healthy individual from Tamil Nadu State were analyzed and compared with other populations of India and the world. HLA‐A, B and C alleles frequencies and their haplotype frequencies were determined by high‐resolution typing of genomic DNA. The analysis revealed that the Nadar caste of South India have several characters shared with East Asian populations consistent with the demographic history of South India, as well as specific features including several unique alleles such as A*03011, A*31011, B*15011, B*3501, B*51011, Cw*02022. In addition, haplotypes such as A*31011‐Cw*02022‐B*3501, A*03011‐Cw*04011‐B*4406 and A*2402101‐Cw*04011‐B*51011 are of high frequency in both these populations but are rare or absent in other populations of India and the world. The study suggests that a comparatively lesser degree of genetic admixture occurred between the South Indian and North Indian racial groups than that between South Indian and East Asian groups.
NQO2 gene is associated with clozapine‐induced agranulocytosis
Authors: Ostrousky O. , Meged S. , Loewenthal R. , Valevski A. , Weizman A. , Carp H. , Gazit E.
Published: November 2003

Abstract:  Clozapine is a dibenzodiazepine neuroleptic with atypical pharmacological and clinical profiles. Treatment with this drug may be complicated with agranulocytosis (AGR). It is likely that defective oxidative mechanism may be the cause of AGR. A candidate gene, dihydronicotinamide riboside (NRH) quinone oxidoreductase 2 (NQO2), which is involved in detoxification of drugs, was selected. This gene has been mapped to the short arm of chromosome six. The gene was studied by single‐strand conformation polymorphism analysis and direct sequencing in 98 schizophrenic patients that were treated with clozapine. Eighteen of these patients developed AGR. Ten polymorphisms in the coding regions, in intron 1, and in the promoter region were found, two of which were novel. Comparisons of the polymorphisms in the first intron in AGR patients and controls suggested that this site might be connected with AGR. Quantitative reverse transcriptase‐polymerase chain reaction analysis showed that the level of NQO2 mRNA is low in AGR patients compared with the control group. Such a reduction in message suggests that the NQO2 gene may be involved in the development of clozapine‐induced AGR.
Soluble HLA‐DR and soluble CD95 ligand levels in pregnant women with antiphospholipid syndromes
Authors: Rebmann V. , Ronin‐Walknowska E. , Sipak‐Szmigiel O. , Miklaszewicz A. , Czajkowska E. , Grosse‐Wilde H.
Published: November 2003

Abstract: Antiphospholipid syndrome (APS) is a severe complication in pregnancy that can lead to fetal death in the second or third trimester. As soluble HLA‐DR (sHLA‐DR) molecules are reported to be implicated in the etiology of pregnancy disorders and of autoimmune diseases, we studied sHLA‐DR plasma levels in pregnant women with APS (n = 14) and in women with normal pregnancy (n = 15), in women with high‐risk pregnancies such as preeclampsia (PE; n = 20) and intrauterine growth retardation (IUGR; n = 10) and in fertile non‐pregnant women (n = 29). The sHLA‐DR levels of pregnant women were assessed during the third trimester, at labor, in the first week, and in the third month of puerperium. The results obtained were compared with soluble CD95 ligand (sCD95L), an important signal molecule in the apoptosis pathway. The sHLA‐DR levels in pregnant women with APS were approximately three times higher (mean 1.48 ± 0.15 µg/ml) during the whole observation period than in fertile non‐pregnant women (0.54 ± .06 µg/ml) and nearly double in women with high risk (PE, 0.91 ± 14 µg/ml; IUGR, 0.94 ± .21 µg/ml) and in normal pregnancies (0.74 ± 0.13 µg/ml). Furthermore, sHLA‐DR levels of pregnant women with APS were positively correlated with the serum concentration of anti‐anticardiolipin immunoglobulin G antibodies. For sCD95L plasma levels, no substantial variations were found among the different groups above. In pregnant women with APS, however, sHLA‐DR levels were positively correlated with sCD95L levels. Further studies should clarify the functional involvement of sHLA‐DR molecules in the induction of CD95/CD95L‐mediated apoptosis pathway that may play a crucial role in the pathology of pregnancies complicated by APS.
HLA class II diversity in seven Amerindian populations. Clues about the origins of the Aché
Authors: Tsuneto L.T. , Probst C.M. , Hutz M.H. , Salzano F.M. , Rodriguez‐Delfin L.A. , Zago M.A. , Hill K. , Hurtado A.M. , Ribeiro‐dos‐Santos A.K.C. , Petzl‐Erler M.L.
Published: November 2003

Abstract:  The study of the HLA variability of Native American populations revealed several alleles specific to one or more of the Latin American indigenous populations. The analysis of Amerindian groups distributed all over the continent might inform about the area of origin and the dispersal of these alleles and shed light on the evolution of this remarkable polymorphism. Moreover, HLA alleles and haplotypes are excellent markers to understand the genetic relationships between populations. For these reasons, we characterized the HLA class II polymorphism in seven South American Amerindian populations and compared the results with those previously reported for other Amerindian groups. The Guarani‐Kaiowá (n = 160) and Guarani‐Ñandeva (n = 87) were from the Brazilian state of Mato Grosso do Sul, the Guarani‐M'byá (n = 93) and Kaingang (n = 235) from Paraná state, the Aché (n = 89) from eastern Paraguay, the Quechua (n = 44) from Andean Peru. From Amazonia, a heterogeneous group was analyzed (n = 45). The most frequent alleles and haplotypes are common also in other Amerindian populations. Each HLA‐DRB1 allele was typically found in combination with just one DQA1‐DQB1 haplotype, most likely as a result of some form of random genetic drift and reduced gene flow from non‐Amerindians. The frequency distribution differed significantly among all populations, although differences were less pronounced between the Guarani subgroups. Marker alleles allowed an estimate of European and sub‐Saharan African gene flow into these populations: Quechua 23%, Guarani‐Ñandeva 14%, Kaingang 7%, Guarani‐M'byá 4%, Guarani‐Kaiowá, Amazonia, and Aché 0%. Interestingly, the DRB1*1413 allele, previously found only among the Guarani‐M'byá (frequency 15%), appeared in the Aché (8%). The relationship of the Aché to other Amerindian populations is unclear, and this finding reveals a link with the Guarani. On the basis of genetic distance and the HLA allele/haplotype set, we propose that the Aché are differentiated Tupi‐Guarani group, most closely related to the Guarani‐M'byá.