bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring for potentially xenozoonotic viruses in New Zealand pigs
Authors: Garkavenko Olga , Muzina Maria , Muzina Zeljko , Powels Kevin , Elliott Robert B. , Croxson Margaret C.
Published: December 2003

Shortage of human donor organs for transplantation has prompted evaluation of animals as an alternative donor source. Pigs are the most acceptable candidate animals but issues of xenozoonozes remain. Despite careful monitoring of high‐health‐status (HHS) pigs, there is still a risk that their tissues may carry infectious agents. Furthermore, pathogens which are significant in xenotransplantation are not necessarily those of veterinary importance. The detection of these potentially transmissible infectious agents may require the development and application of new surveillance technologies. We present data on monitoring for five potentially xenotic viruses in New Zealand pig herds, namely pig cytomegalovirus (PCMV), pig lymphotropic herpesvirus (PLHV), encephalomyocarditis virus (EMCV), pigcircovirus (PCV), and hepatitis E virus (HEV). These five viruses are either potentially oncogenic, establish persistent infection, or are known to be zoonotic. This study has expanded significantly the information on porcine viruses in New Zealand. Using this information, it is now possible to complete protocols for monitoring pig herds and tissues prior to their use in xenotransplantation. The study resulted in selection of a possible source herd for swine‐to‐human islet transplantation. J. Med. Virol. 72:338–344, 2004. © 2004 Wiley‐Liss, Inc.
Cytomegalovirus and adenovirus infections and diseases among 75 paediatric unrelated allogeneic bone marrow transplant recipients
Authors: Morfin Florence , Boucher Anne , Najioullah Fatiha , Bertrand Yves , Bleyzac Nathalie , Poitevin‐Later Françoise , Bienvenu Françoise , Simonet Violaine , Galambrun Claire , Philippe Noël , Aymard Michèle , Thouvenot Danielle , Souillet Gérard
Published: December 2003

Viral infections remain a major complication of allogeneic bone marrow transplantation. A population of children who underwent unrelated allogeneic bone marrow transplantation in a single centre has been followed‐up for viral infections and diseases. We describe the detection of cytomegalovirus (CMV) and adenovirus among 75 children transplanted between 1989 and 2000. CMV was detected among 22 patients (29%) and adenovirus among 19 patients (25%); they were associated with clinical diseases in 10 and 8 patients, respectively. Four patients had adenovirus and CMV coinfection. The obvious risk factor for CMV infection is seropositivity of the recipient prior to transplantation. Adenovirus is detected significantly more frequently when conditioning regimen includes anti‐thymocyte or anti‐lymphocyte globulin. Diseases associated with adenovirus have been correlated with a significantly higher mortality rate, stressing the need for the implementation of a systematic virological survey for this virus and for the evaluation of therapeutic protocols including new molecules. J. Med. Virol. 72:257–262, 2004. © 2004 Wiley‐Liss, Inc.
Functional alterations in immature cultured rat hippocampal neurons after sustained exposure to static magnetic fields
Authors: Hirai Takao , Yoneda Yukio
Published: December 2003

In cultured rat hippocampal neurons, gradual increases were seen in the expression of microtubule‐associated protein‐2 (MAP‐2), neuronal nuclei (NeuN) and growth‐associated protein‐43 (GAP‐43), in proportion to increased duration, up to 9 days in vitro (DIV). Sustained exposure to static magnetic fields at 100 mT for up to 9 DIV significantly decreased expression of MAP‐2 and NeuN in cultured rat hippocampal neurons without markedly affecting GAP‐43 expression. Although a significant increase was seen in the expression of glial fibrillary acidic protein (GFAP) in hippocampal neuronal preparations cultured for 6–9 DIV under sustained magnetism, GFAP and proliferating cell nuclear antigen expression were not affected markedly in cultured astrocytes prepared from rat hippocampus and neocortex, irrespective of cellular maturity. No significant alteration was seen in cell survivability of hippocampal neurons or astrocytes cultured under sustained magnetism. In hippocampal neurons cultured for 3 DIV under sustained magnetism, marked mRNA expression was seen for N‐methyl‐D‐aspartate (NMDA) receptor subunits, NR1, NR2A‐2C, NR2D, and NR3A. In addition, significant potentiation of the ability of NMDA to increase intracellular free Ca2+ ions was observed. Differential display analysis revealed a significant decrease in mRNA expression for the transcription factor ALF1 in response to sustained magnetism for 3 DIV. These results suggest that sustained exposure to static magnetic fields may affect cellular functionality and maturity in immature cultured rat hippocampal neurons through modulation of expression of particular NMDA receptor subunits. © 2003 Wiley‐Liss, Inc.
Transient focal ischemia in rat brain differentially regulates mRNA expression of protease‐activated receptors 1 to 4
Authors: Rohatgi T. , Henrich‐Noack P. , Sedehizade F. , Goertler M. , Wallesch C.W. , Reymann K.G. , Reiser G.
Published: December 2003

Degeneration or survival of cerebral tissue after ischemic injury depends on the source, intensity, and duration of the insult. In the model of focal ischemia, reduced blood flow results in a cascade of pathophysiologic events, including inflammation, excitotoxicity, and platelet activation at the site of injury. One serine protease that is associated closely with and produced in response to central nervous system (CNS) injury is thrombin. Thrombin enters the injury cascade in brain either via a compromised blood‐brain barrier or possibly from endogenous prothrombin. Thrombin mediates its action through the protease‐activated receptor family (PAR‐1, ‐3, and ‐4). PARs belong to the superfamily of G protein‐coupled receptors with a 7‐transmembrane domain structure and are activated by proteolytic cleavage of their N‐terminus. We showed that thrombin can be neuroprotective or deleterious when present at different concentrations before and during oxygen‐glucose deprivation, an in vitro model of ischemia. We examined the change in mRNA expression levels of PAR‐1 to 4 as a result of transient focal ischemia in rat brain, induced by microinjection of endothelin near the middle cerebral artery. Using semiquantitative reverse transcription‐polymerase chain reaction (RT‐PCR) analysis, after ischemic insult on the ipsilesional side, PAR‐1 was found to be downregulated significantly, whereas PAR‐2 mRNA levels decreased only moderately. PAR‐3 was upregulated transiently and then downregulated, and PAR‐4 mRNA levels showed the most striking (2.5‐fold) increase 12 hr after ischemia, in the injured side. In the contralateral hemisphere, mRNA expression was also affected, where decreased mRNA levels were observed for PAR‐1, ‐2, and –3, whereas PAR‐4 levels were reduced only after 7 days. Taken together, these data suggest involvement of the thrombin receptors PAR‐1, PAR‐3, and PAR‐4 in the pathophysiology of brain ischemia. © 2003 Wiley‐Liss, Inc.
Residues 17–20 and 30–35 of beta‐amyloid play critical roles in aggregation
Authors: Liu Ruitian , McAllister Chad , Lyubchenko Yuri , Sierks Michael R.
Published: December 2003

We examined the effects of co‐incubating nine different Aβ peptide fragments with full‐length Aβ1–40 (Aβ40) on protein aggregation. Six fragments enhanced aggregation of Aβ40 (Aβ1–28, 12–28, 17–28, 10–20, 25–35 and 17–40), while three others did not (Aβ1–11, 1–16, and 20–29). All of the peptides that enhanced aggregation contained either residues 17–20 or 30–35, indicating the importance of these regions for promoting aggregation of full‐length Aβ. Aβ25–35 in particular increased both the rate and extent of aggregation of Aβ40 considerably as indicated by fluorescence staining. Atomic force microscope imaging (AFM) indicates the increase in fluorescence staining with Aβ25–35 is primarily due to increased formation of oligomers and protofibrils rather than formation of large amyloid fibrils. AFM images of Aβ25–35 when incubated alone also indicate formation of aggregates and long thin filaments. The increase in formation of the small toxic oligomeric morphology of Aβ40, along with formation of Aβ25–35 oligomers and thin filaments, represent two different potential pathways for Aβ25–35 toxicity. The critical roles of residues 17–20 and 30–35 of Aβ provide further insight into mechanism that underlie the formation of toxic aggregates in Alzheimer Disease (AD) and suggest targets for the design of β‐sheet breakers to modulate the aggregation and inhibit toxicity of full‐length Aβ. © 2003 Wiley‐Liss, Inc.
Dynamics of oligodendrocyte responses to anterograde axonal (Wallerian) and terminal degeneration in normal and TNF‐transgenic mice
Authors: Drøjdahl Nina , Fenger Christina , Nielsen Helle H. , Owens Trevor , Finsen Bente
Published: December 2003

The inflammatory cytokine tumour necrosis factor (TNF) can both induce oligodendrocyte and myelin pathology and promote proliferation of oligodendrocyte progenitor cells and remyelination. We have compared the response of the oligodendrocyte lineage to anterograde axonal (Wallerian) and terminal degeneration and lesion‐induced axonal sprouting in the hippocampal dentate gyrus in TNF‐transgenic mice with the response in genetically normal mice. Transectioning of the entorhino‐dentate perforant path axonal projection increased hippocampal TNF mRNA expression in both types of mice, but to significantly larger levels in the TNF‐transgenics. At 5 days after axonal transection, numbers of oligodendrocytes and myelin basic protein (MBP) mRNA expression in the denervated dentate gyrus in TNF‐transgenic mice had increased to the same extent as in nontransgenic littermates. At this time, transgenics showed a tendency towards a greater increase in the number of juxtaposed, potentially proliferating oligodendrocytes. Noteworthy, at day 5 we also observed upregulation of MBP mRNA expression in adjacent hippocampal subregions with lesion‐induced axonal sprouting, which were devoid of axonal degeneration, raising the possibility that sprouting axons provide trophic stimuli to the oligodendrocyte lineage. Twenty‐eight days after lesioning, oligodendrocyte numbers and MBP mRNA expression were reduced to near normal levels. However, oligodendrocyte densities in the TNF‐transgenic mice were significantly lower than in nontransgenics. We conclude that the early response of the oligodendrocyte lineage to axonal lesioning and lesion‐induced axonal sprouting appears unaffected by the supranormal TNF levels in the TNF‐transgenic mice. TNF may, however, have long‐term inhibitory effects on the oligodendrocyte response to axonal lesioning. © 2003 Wiley‐Liss, Inc.
Down‐regulation of caveolin‐1 in glioma vasculature: Modulation by radiotherapy
Authors: Régina Anthony , Jodoin Julie , Khoueir Paul , Rolland Yannève , Berthelet France , Moumdjian Robert , Fenart Laurence , Cecchelli Romeo , Demeule Michel , Béliveau Richard
Published: December 2003

Primary brain tumors, particularly glioblastomas (GB), remain a challenge for oncology. An element of the malignant brain tumors' aggressive behavior is the fact that GB are among the most densely vascularized tumors. To determine some of the molecular regulations occuring at the brain tumor endothelium level during tumoral progression would be an asset in understanding brain tumor biology. Caveolin‐1 is an essential structural constituent of caveolae that has been implicated in mitogenic signaling, oncogenesis, and angiogenesis. In this work we investigated regulation of caveolin‐1 expression in brain endothelial cells (ECs) under angiogenic conditions. In vitro, brain EC caveolin‐1 is down‐regulated by angiogenic factors treament and by hypoxia. Coculture of brain ECs with tumoral cells induced a similar down‐regulation. In addition, activation of the p42/44 MAP kinase is demonstrated. By using an in vivo brain tumor model, we purified ECs from gliomas as well as from normal brain to investigate possible regulation of caveolin‐1 expression in tumoral brain vasculature. We show that caveolin‐1 expression is strikingly down‐regulated in glioma ECs, whereas an increase of phosphorylated caveolin‐1 is observed. Whole‐brain radiation treatment, a classical way in which GB is currently being treated, resulted in increased caveolin‐1 expression in tumor isolated ECs. The level of tumor cells spreading around newly formed blood vessels was also elevated. The regulation of caveolin‐1 expression in tumoral ECs may reflect the tumoral vasculature state and correlates with angiogenesis kinetics. © 2003 Wiley‐Liss, Inc.
Dynein: An ancient motor protein involved in multiple modes of transport
Authors: Vallee Richard B. , Williams John C. , Varma Dileep , Barnhart Lora E.
Published: December 2003

Cytoplasmic dynein has long been thought to be responsible for retrograde axonal transport. As the number of cellular roles for this multifunctional protein has expanded, the complexity of its contribution to axonal transport has increased. In this article the increasing evidence for a role for cytoplasmic dynein in anterograde as well as retrograde transport is discussed. The current status of the complex dynein cargo‐binding mechanism is evaluated. Finally, recent genetic evidence supporting a role in axonal transport and revealing a role in neurodegenerative conditions is reviewed. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 189–200, 2004
Mechanisms of neurotrophin receptor vesicular transport
Authors: Yano Hiroko , Chao Moses V.
Published: December 2003

Accumulating evidence has indicated that neurotrophin receptor trafficking plays an important role in neurotrophin‐mediated signaling in developing as well as mature neurons. However, little is known about the molecular mechanisms and the components of neurotrophin receptor vesicular transport. This article will describe how neurotrophin receptors, Trk and p75 neurotrophin receptor (p75NTR), are intimately involved in the axonal transport process. In particular, the molecules that may direct Trk receptor trafficking in the axon will be discussed. Finally, potential mechanisms by which receptor‐containing vesicles link to molecular cytoskeletal motors will be presented. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 244–257, 2004
Signaling endosome hypothesis: A cellular mechanism for long distance communication
Authors: Howe Charles L. , Mobley William C.
Published: December 2003

The kinetics of signaling endosome retrograde transport along axons is analyzed and offered as evidence that such transport is more efficient than diffusion or calcium wave‐based signaling systems over even relatively small distances. Evidence is provided to support the signaling endosome hypothesis and to expand the hypothesis to include signaling in many cell types and many cellular dimensions. Finally, a saltatory, regenerating inositol 1,4,5‐trisphosphate wave model is offered to reconcile current discrepancies in the literature regarding endosomal‐based retrograde signaling. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 207–216, 2004
Conformational analysis of fluoroacetoxime and of its O‐methyl ether by 1H, 13C and 15N NMR and theoretical calculations
Authors: Tormena Cláudio F. , Rittner Roberto , Abraham Raymond J. , Basso Ernani A. , Fiorin Barbara C.
Published: December 2003

The solvent dependence of the 1H, 13C and 15N NMR spectra of (E)‐fluoroacetoxime [(E)‐FAO] and of (E)‐fluoroacetoxime O‐methyl ether [(E)‐FAOME], was examined and the HF, CF and NF couplings are reported. Density functional theory (DFT) at the B3LYP/6–311++g(2df,2p) level with ZPE (zero point energy) correction was used to obtain the rotamer geometries. In both (E)‐FAO and (E)‐FAOME the DFT method gave two energy minima corresponding to the cis (F—C—CN, 0°) and gauche (F—C—CN, 124.1°) rotamers. In contrast, in (Z)‐FAO the DFT method gave only one energy minimum corrsponding to the trans rotamer. The 4JHF and 1JCF couplings in (E)‐FAO were analyzed by solvation theory assuming the cis and gauche forms to give $E_{cis}-E_{gauche} = 3.3 \, {\rm kcal\, mol}^{-1}$ in the vapor phase, decreasing to 1.54 kcal mol−1 in CCl4 and −1.19 kcal mol−1 in DMSO (1 kcal=4.184 kJ. In (E)‐FAOME the observed couplings, when analysed similarly by solvation theory, gave $E_{cis}-E_{gauche} = 2.2 \,{\rm kcal\, mol}^{-1}$ in the vapor phase, 0.91 kcal mol−1 in CCl4 and −1.18 kcal mol−1 in DMSO. The 3JNF coupling was independent of the molecular conformation, as it did not change with the solvent polarity. Copyright © 2003 John Wiley & Sons, Ltd.
High‐performance concrete buildings for the new millennium
Authors: Kwan A K H , Au F T K , Lee P K K
Published: December 2003

Traditionally, the structural design of concrete buildings has been focused primarily on the provision of a certain minimum level of safety that is acceptable to the general public. After many years of research and development in structural analysis and design methods, there are no longer any major difficulties in ensuring the safety of building structures under normal usage. Nowadays, occupants, owners, developers and society at large are demanding more, including better serviceability, functionality, durability, structural health assurance, repairability, environmental friendliness and sustainability. All these call for a higher performance of building structures in a more general sense. This paper discusses this issue and advocates changing our design philosophy and strategy to meet the challenge of designing high‐performance concrete buildings for the new millennium.
NASA technology assessment using real options valuation
Authors: Shishko Robert , Ebbeler Donald H. , Fox George
Published: December 2003

We examine the use of real options valuation in the context of prioritizing advanced technologies for NASA funding. Further, we offer a set of computational procedures that quantifies the option value of each technology. Other researchers have applied a real options framework to private sector investments. In the case of NASA investments in advanced technologies, the underlying products, which must be used to justify the investments, are space‐related scientific results and discoveries from completed missions to be shared worldwide. As in the private sector, uncertainty plays a significant role in the motivation to use real options in NASA. Uncertainty in NASA technology investments can be classified as development risk and programmatic risk (whether missions using the technology will actually fly). The latter might be called the technology “market risk.” We carried out the approach on a number of planetary exploration technologies. We illustrate the detailed calculations using one of them—lightweight propellant tank technology. © 2003 Wiley Periodicals, Inc. Syst Eng 7: 1–12, 2004
Hydrologic variation during the last 170,000 years in the southern hemisphere tropics of South America
Authors: Fritz Sherilyn C. , Baker Paul A. , Lowenstein Tim K. , Seltzer Geoffrey O. , Rigsby Catherine A. , Dwyer Gary S. , Tapia Pedro M. , Arnold Kimberly K. , Ku Teh-Lung , Luo Shangde
Published: December 2003

Despite the hypothesized importance of the tropics in the global climate system, few tropical paleoclimatic records extend to periods earlier than the last glacial maximum (LGM), about 20,000 years before present. We present a well-dated 170,000-year time series of hydrologic variation from the southern hemisphere tropics of South America that extends from modern times through most of the penultimate glacial period. Alternating mud and salt units in a core from Salar de Uyuni, Bolivia reflect alternations between wet and dry periods. The most striking feature of the sequence is that the duration of paleolakes increased in the late Quaternary. This change may reflect increased precipitation, geomorphic or tectonic processes that affected basin hydrology, or some combination of both. The dominance of salt between 170,000 and 140,000 yr ago indicates that much of the penultimate glacial period was dry, in contrast to wet conditions in the LGM. Our analyses also suggest that the relative influence of insolation forcing on regional moisture budgets may have been stronger during the past 50,000 years than in earlier times.
Latest Pleistocene paleoecology of Jefferson's ground sloth (Megalonyx jeffersonii) and elk-moose (Cervalces scotti) in northern Illinois
Authors: Schubert Blaine W. , Graham Russell Wm. , McDonald H. Gregory , Grimm Eric C. , Stafford Thomas W.
Published: December 2003

New records of Jefferson's ground sloth (Megalonyx jeffersonii) and elk-moose (Cervalces scotti) from Lang Farm provide the first precise temporal correlation of these taxa with the specific environments inhabited by them near the time of their extinction. Six AMS14C measurements establish an age of 11,405 ± 5014C yr B.P. for Lang FarmCervalcesand an age of 11,430 ± 60 or 11,485 ± 4014C yr B.P. for theMegalonyx. These measurements represent the youngest14C dates for these two genera based on direct dating. Comparison of the dates with pollen data from northern Illinois indicates that these species inhabited a nonanalog environment that was transitional from mid-latitude tundra to mixed conifer and deciduous woodland. Although spruce (Piceasp.) was dominant, it was less abundant than prior to 12,50014C yr B.P. The presence of black ash (Fraxinus nigra) and fir (Abiessp.) indicates a wet climate and heavy winter precipitation. This may have been the preferred habitat forCervalcesbecause of its narrow geographic range. However, this habitat type was only one of many occupied byMegalonyxas indicated by its broad geographic distribution.
Chalcone dimethylallyltransferase from Morus nigra cell cultures. Substrate specificity studies
Authors: Vitali Alberto , Giardina Bruno , Delle Monache Giuliano , Rocca Filippo , Silvestrini Andrea , Tafi Andrea , Botta Bruno
Published: December 2003

A new prenyltransferase (PT) enzyme derived from the microsomal fractions of cell cultures of Morus nigra was shown to be able to prenylate exclusively chalcones with a 2′,4′‐dihydroxy substitution and the isoflavone genistein. Computational studies were performed to shed some light on the relationship between the structure of the substrate and the enzymatic activity. PT requires divalent cations, particularly Mg2+, to be effective. The apparent K
m values for γ,γ‐dimethylallyldiphosphate and 2′,4′‐dihydroxychalcone were 63 and 142 μM, respectively. The maximum activity of the enzyme was expressed during the first 10 days of cell growth.
Evidence for hetero‐association of transmembrane helices of integrins
Authors: Gottschalk Kay-Eberhard , Kessler Horst
Published: December 2003

Integrins are important transmembrane cell‐surface receptors, which mediate interactions of the cell with other cells or the extracellular matrix. Integrins are heterodimers composed of an α‐ and a β‐subunit. They can switch between different activation states depending on intra‐ or extracellular signals. Inside/out and outside/in signaling is mediated via integrins across the membrane. A biologically important and yet still unanswered question is the role of the transmembrane domains in the signaling event. Here it is shown by simulated annealing/molecular dynamics calculations that recently published structural data of the cytoplasmic domains of integrin αIIbβ3 are supporting a structure with interacting transmembrane helices. This corroborates a model of transmembrane domains that are actively involved in the transmembrane signaling event.
NIRF is a ubiquitin ligase that is capable of ubiquitinating PCNP, a PEST‐containing nuclear protein
Authors: Mori Tsutomu , Li Yuanyuan , Hata Hiroaki , Kochi Hideo
Published: December 2003

We previously reported the association of a novel Np95/ICBP90‐like RING finger protein (NIRF) with a novel PEST‐containing nuclear protein (PCNP). NIRF is a nuclear protein with a ubiquitin‐like domain, a PHD finger, a YDG/SRA domain, Rb‐binding motifs and a RING finger. In this study, we showed that NIRF has auto‐ubiquitination activity, the hallmark of a ubiquitin ligase. PCNP was readily ubiquitinated in 293 and COS‐7 cells, and NIRF ubiquitinated PCNP in vitro as well as in vivo. Considering that NIRF is implicated in cell cycle regulation, these findings suggest that NIRF and PCNP are a ubiquitin ligase and its substrate, respectively, and may constitute a novel signaling pathway with some relation to cell proliferation.
Corticotropin‐releasing factor receptor type 1 is involved in the stress‐induced exacerbation of chronic contact dermatitis in rats
Authors: Kaneko Katsumi , Kawana Seiji , Arai Keiko , Shibasaki Tamotsu
Published: December 2003

Abstract: Cutaneous diseases such as psoriasis and atopic dermatitis are worsened by psychic stress. We attempted to clarify the involvement of the corticotropin‐releasing factor (CRF) receptor (CRFR) in stress‐induced exacerbation of chronic contact dermatitis in rats. Male Wistar rats, in which chronic contact dermatitis had been induced by 2,4,6‐trinitro‐1‐chlorobenzene (TNCB), were exposed to a 1‐h period of electric foot‐shock following intraperitoneal administration of CRA1000, a selective CRFR type 1 (CRFR1) antagonist, or vehicle everyday for 9 days. Histological examination of the skin showed that the epidermis significantly thickened and the number of mast cells in the dermis significantly increased by repeated exposure to stress, and that these changes were blocked by CRA1000. These results suggest that CRFR1 is involved in the stress‐induced exacerbation of chronic contact dermatitis.
Severe central nervous system thrombotic events in hemoglobin Sabine patient
Authors: Pavlovic Sonja , Kuzmanovic Milos , Urosevic Jelena , Poznanic Jelena , Zoranovic Tamara , Djordjevic Valentina , Rasovic Nada , Bunjevacki Gordana , Cvorkov‐Drazic Milica , Colovic Milica
Published: December 2003

Hemoglobin (Hb) Sabine is a rare, unstable Hb variant resulting from the point mutation in codon 91 (CTG → CCG) of β‐globin gene. We report a case of Hb Sabine patient with mild hemolytic anemia, unusually high Hb F level and severe central nervous system thrombotic disturbances. We have tried to elucidate possible genetic background of this unusual Hb Sabine phenotype. Extremely high level of Hb F and rather mild anemia in our patient could be partially explained by the presence of Gγ Xmn I polymorphism. This case of Hb Sabine, unlike all other reported to date, shows extremely severe thromboembolic complications. It is our opinion that the hypercoagulable state described in thalassemia is not the only factor responsible for this specific clinical state. The presence of MTHFR C677T mutation in heterozygous state found in our patient and unstable Hb Sabine molecules could contribute to development of thromboembolic phenomena. However, it remains unclear whether other factors participate in pathogenesis of the disease. In this paper we emphasize different genetic background of father and son both affected with Hb Sabine, but with markedly different severity of the disease.
Ida‐FLAG plus imatinib mesylate‐induced molecular remission in a patient with chemoresistant Ph1(+) acute myeloid leukemia
Authors: Viniou Nora‐Athina , Vassilakopoulos Theodoros P. , Giakoumi Xanthi , Mantzouranis Marina , Pangalis Gerassimos A.
Published: December 2003

Imatinib mesylate is a potent, selective inhibitor of the tyrosine kinase activity of bcr‐abl,which is now established as the state‐of‐the‐art treatment for chronic, accelerated or even blastic phase of Philadelphia‐positive [Ph1(+)] chronic myelogenous leukemia. It is also active in Ph1(+) acute lymphoblastic leukemia, but its role in Ph1(+) acute myeloid leukemia (AML) is less well investigated. We report here a patient with chemoresistant Ph1(+) AML, who responded promptly to one cycle of Ida‐FLAG second‐line chemotherapy by achieving complete morphologic, immunophenotypic, and cytogenetic remission but not a molecular one. The addition of imatinib mesylate led to a molecular remission, which is sustained for 10 months so far.
Monitoring grass swards using imaging spectroscopy
Authors: Schut A. G. T. , Ketelaars J. J. M. H.
Published: December 2003

The potential of an imaging spectroscopy system with high spatial (0·16–1·45 mm2) and spectral resolution (5–13 nm) was explored for monitoring light interception and biomass of grass swards. Thirty‐six Lolium perenne L. mini‐swards were studied for a total of eleven consecutive growth periods. Hyperspectral images and light interception (LI) were recorded twice weekly. On two dates ground cover was scored visually (GCv). At harvest, leaf area index (LAI), fresh‐matter yield and dry‐matter yield (DMY) were determined. Classification of images yielded several estimates of the image ground cover (GCi) and the index of reflection intensity (IRI). The GCi was highly correlated with GCv ( = 0·94), LAI ( = 0·88) and LI ( = 0·95, for dense swards under cloudy skies). However, the relationship between GCi and LI depended on sky conditions and sward structure. Under cloudy skies, LI was linearly related to GCi, whereas under clear skies, this relation was logistic. Regression analysis of GCi and yields showed correlations with of between 0·75 and 0·82. The mean error of DMY estimates was 340 kg. In conclusion, estimates of GCi and IRI can be used to predict DMY, even for high yield levels (up to 3500 kg DM ha−1), allowing accurate, non‐destructive monitoring of biomass and light interception of grass swards.
Natural course of gestational diabetes mellitus: long term follow up of women in the SPAWN study
Authors: Linné Yvonne , Barkeling Britta , Rössner Stephan
Published: December 2003

Objectives
Long term follow up women with gestational diabetes mellitus (GDM).

Design
Case–control study.

Setting
Academic obesity unit.

Population
Women earlier identified as having gestational diabetes mellitus.

Method
Twenty‐eight women diagnosed with GDM in 1984–1985, and a control group (n= 52) who gave birth at the same time performed a 2‐h oral glucose tolerance test 15 years later. Basic anthropometry and questions about various aspects of eating and exercise habits were furthermore obtained.

Results
Ten women (35%) in the GDM group were diagnosed with type 2 diabetes mellitus and none in the control group (P < 0.001). Mean BMI in the diabetic group was 27.4 kg/m2 and in the non‐diabetic GDM group 24.6 kg/m2 (P < 0.05). The mean weight gain since the first child was 8.4 kg in all GDM versus 8.1 kg in controls (ns). The women who developed type 2 diabetes mellitus, however, gained 15.1 kg since the birth of their first child (P < 0.05).

Conclusions
Women who are diagnosed with GDM have a considerably higher risk of developing type 2 diabetes mellitus later in life. Despite a close medical monitoring during pregnancy, the further follow up within the health care system and information about long term consequences of GDM for later type 2 diabetes mellitus development seems to be generally lacking. More active strategies for future weight control and lifestyle advice after delivery might therefore be indicated for women with GDM.
Economic consequences of preterm birth and low birthweight
Authors: Petrou Stavros
Published: December 2003

The high rates of mortality and morbidity arising from preterm birth and low birthweight impose an immense burden on the health, education and social services and on families. This was evaluated in several economic studies published in the 1970s and early 1980s, but an ability to intervene effectively to increase survival has transformed neonatal care over the past two decades. In addition, the relative prices of resource inputs are vastly different. This paper surveys the scientific literature on the economic consequences of preterm birth and low birthweight, including: (1) studies, which estimate the economic costs of the conditions and (2) economic evaluations of primary and secondary prevention and treatment strategies. This paper summarises the scope and scientific quality of the published evidence, identifies gaps in our knowledge and considers the future research agenda in this area.
Fetuses with Down's Syndrome detected by prenatal screening are more likely to abort spontaneously than fetuses with Down's Syndrome not detected by prenatal screening
Authors: Leporrier Nathalie , Herrou Michel , Morello Rémy , Leymarie Pierre
Published: December 2003

Objective
Pregnancy with Down's Syndrome is often terminated by miscarriage. We have investigated whether prenatal screening would lead preferentially to the identification of fetuses with Down's Syndrome prone to abort spontaneously.

Design
A comparison between the observed and the expected decrease in the prevalence of Down's Syndrome at term following extensive prenatal screening.

Setting
A study from 1990 to 1998 in a limited and well controlled area of western France (Basse Normandie), with a birth rate close to 20,000 a year.

Population
Women under 38 years of age among whom prenatal screening for Down's Syndrome using biochemical tests and ultrasound findings became progressively extensive in this era.

Methods
Our study was based on the registration of Down's Syndrome cases detected prenatally from screening, and live births with Down's Syndrome. Fetal loss rate in the population of prenatally detectable Down's Syndrome was evaluated by comparing the increase in detection of cases of Down's Syndrome following prenatal screening with the expected decrease in the number of cases of Down's Syndrome at birth. The results obtained were compared with published data on the rates of fetal losses postulated to occur among fetuses with Down's Syndrome.

Main outcome measures
Comparison of the potential fetal loss rate in a population in whom Down's Syndrome was detected prenatally with the expected fetal loss rate of unselected ones.

Results
Prenatal screening resulted in a significant (42%) decrease (P < 0.001) in the prevalence at term of the disorder. Among the 53 fetuses with Down's Syndrome detected prenatally during the last three years of the study, about 50% would have aborted spontaneously if the pregnancy had been allowed to continue. This figure was significantly higher (P < 0.002) than expected on the basis of results from the literature, indicating that current estimates of miscarriage rates among fetuses with Down's Syndrome do not apply to the selected group of cases detectable from prenatal screening.

Conclusions
Our results suggest that fetuses with Down's Syndrome detectable prenatally from screening are more likely to abort spontaneously than fetuses with Down's Syndrome which are not detected.
Forearm blood flow in pre‐eclampsia
Authors: Bowyer Lucy , Brown Mark A. , Jones Mike
Published: December 2003

Objective
1. To characterise the forearm vascular reactivity of women with pre‐eclampsia in the third trimester of pregnancy and compare it with that in normal or gestational hypertensive pregnancies. 2. To document female sex steroid (oestradiol, progesterone, oestriol and βhCG) levels in the three groups of women.

Design
Forearm blood flow was measured by venous occlusion plethysmography during intra‐arterial infusion of saline and vasoactive substances: angiotensin II, sodium nitroprusside, acetylcholine and NG‐monomethyl‐l‐arginine (l‐NMMA).

Setting
Research laboratory at St George Hospital, Kogarah, Sydney, Australia.

Sample
Fifteen non‐pregnant women in the follicular phase of the menstrual cycle, 15 third trimester normal pregnant women, 13 women in the third trimester with gestational hypertension and 15 women with pre‐eclampsia.

Main outcome measures
Changes in forearm blood flow in response to vasoactive substances.

Results
Normal pregnant women had higher baseline forearm blood flow than non‐pregnant women, decreased vasodilator responses to sodium nitroprusside and reduced vasoconstrictor responses to angiotensin II. No difference in response to angiotensin II, sodium nitroprusside or l‐NMMA was found among normal pregnant, pre‐eclampsia or gestational hypertension women, but vasodilatory responses of pre‐eclamptic women to acetylcholine were reduced compared with normal pregnant women. Higher serum progesterone levels were found in women with pre‐eclampsia and gestational hypertension than in normal pregnancy.

Conclusion
The hyperdynamic circulation of normal pregnancy is characterised by refractoriness to angiotensin II but this is not altered in pre‐eclampsia. Pre‐eclamptic women demonstrate a reduced vasodilator response to acetylcholine which, in the absence of any alteration in response to l‐NMMA, implies that factors other than nitric oxide deficiency mediate the vasoconstriction of pre‐eclampsia.
Outcomes of pregnancies in women with type 1 diabetes in Scotland: a national population‐based study
Authors: Penney Gillian C. , Mair Grant , Pearson Donald W.M. ,   On behalf of the Scottish Diabetes in Pregnancy Group listed on page 318
Published: December 2003

Objective
To determine the outcomes of pregnancies in women with pre‐existing, type 1 diabetes.

Design
Prospective, population‐based cohort.

Setting
Scotland.

Population
All 273 women with type 1 diabetes with a pregnancy ending (in miscarriage, abortion or delivery) during the 12 months (from April 1, 1998 to March 31, 1999).

Methods
Pregnancies identified prospectively by clinicians in each hospital; outcome data collected from case records and from Scottish national data sets.

Main outcome measures
Perinatal and infant mortality, congenital anomaly and birthweight.

Results
Of the 273 pregnancies, 40 (14.7%) ended in miscarriage, 20 (7.3%) in abortion and 213 (78%) in delivery. Three deliveries were twin births, thus 216 babies were born. Stillbirth rate (4/216): 18.5 (95% CI 5.1–46.8) per 1000 total births; perinatal mortality rate (6/216): 27.8 (95% CI 10.2–59.4) per 1000 births. There were 13 verified congenital anomalies (in six abortions and seven live births), anomaly rate: 60 (95% CI 32–101) per 1000 total births. Among 208 singleton, live born infants, the mean birthweight was 3427 g. Standardised birthweight scores, relative to a reference population, showed a unimodal distribution, shifted to the right (mean, 1.57 SD).

Conclusions
In an unselected population, adverse outcomes remain more common among the infants of mothers with type 1 diabetes than in the general population. The targets of the St Vincent Declaration of 1989 have not been met. Improvements may be gained by increases in provision of prepregnancy care and in the proportion of pregnancies that are planned. However, further research is needed to clarify the root causes of adverse outcomes in the pregnancies of women with diabetes.
Cling film as a barrier against CJD in Goldmann‐type applanation tonometry
Authors: Davies Leon N. , Bartlett Hannah E. , Dunne Mark C. M.
Published: December 2003

Purpose:  To determine the feasibility of taking intra‐ocular pressure (IOP) readings with Goldmann‐type applanation tonometer probe covered with cling film to avoid transmission of Creutzfeldt–Jakob disease (CJD).

Methods:  Data were collected on two occasions from the right eyes of 30 healthy subjects using a Perkins applanation tonometer. On each occasion, a single tonometry measurement was made with and without cling film covering.

Results:  Cling film covering brought about a statistically significant IOP bias (−0.8 mmHg on first occasion and −1.17 mmHg on second occasion). The 95% limits of agreement, between readings made with and without cling film covering, were ±3.4 mmHg on first occasion; ±2.5 mmHg on second occasion. A statistically significant reduction of inter‐sessional repeatability was observed for readings taken with cling film (±5.2 mmHg) compared to those made without (±3.9 mmHg).

Conclusions:  Even if the above findings are found to be acceptable, given the known intra‐subject variations of this type of tonometry (±4 mmHg), ethical and legal considerations relating to the barrier properties of cling film are likely to prevent its routine use by optometrists.
How big does a coloured overlay have to be?
Authors: Waldie Michelle , Wilkins Arnold
Published: December 2003

Coloured overlays and coloured lenses can both increase reading speed, but when they do their colour is not necessarily the same, suggesting that the beneficial effects of a coloured filter might depend upon the area of the visual field that it colours. We investigated the effects of overlays on reading speed and varied the size of the overlay and the colour of the surround. Children who had been assessed with coloured overlays were required to read a passage of randomly ordered common words. The words were printed in black ink as a block of text positioned centrally on an A4 page of white paper in landscape orientation. The speed of reading was compared under four conditions: (1) without an overlay; (2) with an overlay of the chosen colour covering the entire page; (3) with the overlay cut so that it just covered the text but left the margin white; (4) with the overlay of the chosen colour covering the text but with the margin coloured a complementary colour, using a second overlay. The children who were using an overlay read more quickly with the overlay; those who were no longer using the overlay did not. Although the block of text covered less than half the page, the colour and nature of the margin did not affect reading speed significantly. These findings suggest that in order to be effective at improving reading speed an overlay needs to cover the text, but not necessarily the remainder of the page, which means that smaller overlays may sometimes be sufficient.
Loss of nuclear p53 protein in preneoplastic rat hepatocytes is accompanied by Mdm2 and Bcl-2 overexpression and by defective response to DNA damage in vivo
Authors: Van Gijssel Hilde E. , Ohlson Lena C. , Torndal Ulla-Britta , Mulder Gerard J. , Eriksson Lennart C. , Porsch-Hällström Inger , Meerman John H.
Published: December 2003

Previous studies have indicated that isolated preneoplastic rat hepatocytes in vitro fail to induce nuclear p53 protein and fail to block replication in response to genotoxic compounds. This suggests that defects in the protection of genomic integrity are part of their premalignant character. In the present study, we have investigated if similar defects occur in vivo. Preneoplastic glutathione-S-transferase (GST) 7-7-positive foci were induced in male Wistar rats by diethylnitrosamine (DEN) initiation and promotion with 2-acetylaminofluorene (2-AAF)/partial hepatectomy (PH). The response to genotoxic damage was studied by X-irradiation. p53 protein was moderately expressed in nuclei in surrounding hepatocytes. This nuclear p53 staining had decreased 2 weeks after 2-AAF treatment. In foci, the protein was detected in the cytoplasm whereas the nuclei were negative. Levels of p21waf1/cip1 protein were high in nuclei and cytoplasm of surrounding hepatocytes, whereas the expression in foci was low. A low level of Mdm2 in nuclei was observed in surrounding liver, while both Mdm2 and Bcl-2 protein were strongly expressed in the cytoplasm in foci. X-ray exposure further induced nuclear expression of p53, p21waf1/cip1, and Mdm2 in surrounding hepatocytes, but focal nuclei were still negative. DNA replication was strongly reduced by X-irradiation in surrounding hepatocytes, but only partially reduced in the foci. These results indicate that the p53 pathway of response to genomic stress is impaired in preneoplastic cells in vivo. This may support their clonal expansion and their further malignant transformation because protection against genetic damage is diminished.
Long-term therapy of chronic hepatitis B with lamivudine
Authors: Lau Daryl T.-Y. , Khokhar Farooq M. , Doo Edward , Ghany Marc G. , Herion David , Park Yoon , Kleiner David E. , Schmid Peter , Condreay Lynn D. , Gauthier Josée , Kuhns Mary C. , Liang Jake T. , Hoofnagle Jay H.
Published: December 2003

Lamivudine therapy induces improvements in chronic hepatitis B in a high proportion of patients, but prolonged therapy is limited by the development of viral resistance. We analyzed clinical responses and virologic resistance in 27 patients treated continuously with lamivudine for 2 to 4 years. Serum transaminases, hepatitis B virus (HBV) DNA by both branched DNA (bDNA) signal amplification and quantitative polymerase chain reaction were monitored at 4- to 8-week intervals. Virologic resistance to lamivudine was confirmed by the presence of mutations in the YMDD motif of the polymerase gene by restriction fragment-length polymorphism analysis. Serum HBV-DNA levels decreased rapidly in all treated patients, falling by 4 to 5 logs within 1 year. Transaminase levels also decreased and were normal in 70% of patients at 1 year, at which point liver histology had improved in 81% of patients. Viral resistance began to emerge after 8 months of therapy, eventually developing in 14 patients, including 76% of hepatitis B e antigen (HBeAg)-positive patients but only 10% of HBeAg-negative patients. Lamivudine withdrawal led to reappearance of wild-type HBV species, but retreatment led to more rapid reappearance of the mutant virus. Clinical, serum biochemical, and histologic improvements were maintained in the 13 patients who did not develop resistance. Thus, long-term therapy with lamivudine resulted in maintained improvements in virologic, biochemical, and histologic features of disease in most patients with HBeAg-negative chronic hepatitis B and in the subgroup of HBeAg-positive patients with high serum transaminase levels. A high rate of resistance limited efficacy, particularly in patients who remained HBeAg positive on therapy.
Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: A 16-year population-based study
Authors: McMahon Brian J. , Bulkow Lisa , Harpster Annette , Snowball Mary , Lanier Anne , Sacco Frank , Dunaway Eitel , Williams James
Published: December 2003

The benefits of screening hepatitis B surface antigen (HBsAg)-positive carriers for hepatocellular carcinoma (HCC) in terms of long-term survival have not been established. We conducted a prospective 16-year, population-based cohort study to determine the impact of screening for HCC in 1,487 HBsAg-positive Alaska native carriers with alpha-fetoprotein (AFP) determinations every 6 months. Men and nonpregnant women with an elevated AFP level were evaluated for the presence of HCC by ultrasound (US) examination. The long-term survival rate for patients whose HCC was detected by the screening program was compared with a historical control group of Alaska native patients with HCC from the same population who were clinically diagnosed with HCC between 1969 and October 1982, through a National Cancer Institute-sponsored Cancer Registry. Between October 1982 and December 1998, 26,752 AFP determinations in HBsAg carriers were performed. One or more AFP elevations were found in 61 men and 39 nonpregnant women. HCC was diagnosed in 32 patients (24 men and 8 women). HCC tumors less than 6 cm were found in 23 patients; 22 patients had resections, and 1 patient refused a resection. Compared with 12 patients with hepatitis B virus (HBV)-related HCC diagnosed from 1969 to October 1982, before this program, the 5- and 10-year survival rate for the 32 patients with HCC were 42% (P = .008) and 30% (P = .07), respectively. Five- and 10-year tumor-free survival rates for carriers who had a normal AFP level on initial screening and subsequently developed HCC were 29% (P = .004) and 24% (P = .024), respectively. Screening of HBsAg carriers with semiannual AFP was effective in detecting most HCC tumors at a resectable stage and significantly prolonged survival rates when compared with historical controls in this population.
Hamiltonian structure of the fluid electron temperature gradient driven mode
Authors: Gürcan Ö. D. , Diamond P. H.
Published: December 2003

Electron temperature gradient (ETG) driven turbulence can be simply described via reduced fluid equations. In this study, we describe the Hamiltonian structure of the simple curvature-driven ETG model, which is similar to the thermal Rossby wave model studied in atmospheric turbulence. Together with the Hamiltonian that is conserved, another constant of the motion has been identified.