bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Photoinduced Electron Transfer from Zinc‐Porphyrin to Methyl Viologen by Supramolecular Formation between Monoclonal Antibody and Zinc‐Porphyrin
Authors: Harada Akira , Yamaguchi Hiroyasu , Okamoto Kazutake , Fukushima Hiroyuki , Shiotsuki Keizou , Kamachi Mikiharu
Published: January 2008

Abstract Photoinduced electron transfer from tetrakis(4‐carboxy‐phenyl porphyrin)‐zinc complex (Zn‐TCPP) to an acceptor molecule (methyl viologen; MV2+) has been found to be controlled by the complex formation of monoclonal antibody 03‐1 for the porphyrin (TCPP) and Zn‐TCPP. Although there are no ground‐state interactions between Zn‐TCPP and MV2+ for a 2:1 complex of antibody 03‐1 and Zn‐TCPP, the fluorescence of Zn‐TCPP is quenched by the addition of MV2+. The Stern‐Volmer plots and emission lifetime studies show that there is a long‐range electron transfer through the antibody 03‐1.
Singlet Oxygen Adducts of Cholesterol: Photogeneration and Reductive Turnover in Membrane Systems
Authors: Korytowski Witold , Girotti Albert W.
Published: January 2008

Identification of signature products provides a powerful means for establishing whether singlet molecular oxygen (1O2) is a reactive intermediate in a photodynamic process. This approach is particularly attractive for biological systems in which direct physical measurement is difficult because of the short lifetime of 1O2. Among the many possible reporter molecules in a target system, cholesterol (Ch) has the advantage of affording a limited number of readily distinguishable oxidation products, among which are the hydroperoxides 3β‐hydroxy‐5α‐cholest‐6‐ene‐5‐hydroperoxide (5α‐OOH), 3p‐hydroxy‐cholest‐4‐ene‐6a‐hydroperoxide (6α‐OOH) and 3β‐hy‐droxycholest‐4‐ene‐6β‐hydroperoxide (6β‐OOH) that derive specifically from 1O2 addition. The purpose of this study was to compare these species in terms of (1) rates of accumulation in photodynamically treated liposomal membranes; (2) susceptibility to iron‐mediated 1 e‐reduction that triggers chain peroxidative damage; (3) susceptibility to selenoperoxidase (phospholipid hydroperoxide glutathione peroxidase [PHGPX])‐mediated 2 e reduction that protects against such damage and (4) relative toxicity to mammalian cells. Our results indicate that 5α‐OOH is photogenerated at a much greater initial rate than 6α‐OOH or 6β‐OOH. Although liposomal 5α‐OOH, 6α‐OOH, and 6β‐OOH exhibit similar first‐order decay kinetics during iron/ascorbate treatment, the former decays much more slowly during GSH/PHGPX treatment, and is more toxic to L1210 cells. These and related findings suggest that 5α‐OOH is potentially the most damaging ChOOH to arise in photodynamically treated cells.
Mutation Spectrum Induced by Singlet Oxygen in Escherichia coli Deficient in Exonuclease III
Authors: Agnez‐Lima Lucymara F. , Mascio Paolo Di , Napolitano Rita L. , Fuchs Robert P. , Menck Carlos F. M.
Published: January 2008

The repair of singlet oxygen (1O2)‐induced DNA lesions requires several enzymes of the nucleotide and base excision repair pathways, including exonuclease III and endonucle‐ase IV that are known apurinic/apyrunidinic‐endonucleases in Escherichia coli. In order to better understand the relevance of exonuclease III on the repair of these lesions, we investigated the mutagenic events that result from the replication of a 1O2‐damaged plasmid in an exonuclease‐deflcient host (xth). The mutation spectrum in the tRNA supF gene target indicated that the absence of exonuclease III does not change the types of mutations induced by 1O2 (mostly of G:C ← T:A and G:C ← C:G transver‐sions). However, the spectrum shows that the mutations are scattered in the supF gene, which is significatively different from the one obtained in wild‐type bacteria. Thus, exonuclease III may act on the repair of 1O2‐induced lesions altering the DNA repair sequence specificity.
Bisimidazoacridones: Effect of Molecular Environment on Conformation and Photophysical Properties
Authors: Tarasov Sergey G. , Casas‐Finet Jose R. , Cholody Wieslaw M. , Michejda Christopher J.
Published: January 2008

Bisimidazoacridones (BIA) are highly selective antineoplastic and antiviral agents. Ultraviolet‐visible spectroscopy and steady‐state and time‐resolved fluorescence spectroscopy studies were carried out to probe the behavior of BIA in aqueous and nonaqueous (organic solvents, colloid micelles) solutions. Three ranges of fluorescence lifetimes were revealed: ˜0.2‐0.5 ns (presumably reflecting the chromophore–chromophore interaction), ˜1–5 ns (interpreted as linker‐perturbed chromophore decay) and ˜6–12 ns (nonperturbed chromophore decay). The pre‐exponential and steady‐state contributions of these components to the decay signal as well as the data on steady‐state fluorescence intensities, wavelength maxima and bandwidths showed that the BIA conformations in solution were sensitive to the environment and influenced strongly by their propensity to minimize hydrophobic interactions. In water, the molecules tend to adopt condensed conformations that bring the two imi‐dazoacridone moieties into close proximity (resulting in intramolecular fluorescence energy transfer), while in nonaqueous systems the conformations become more relaxed. The transfer from a polar to more lipophilic environment of macromolecules is suggested to be the main driving force for binding of BIA to biomacromolecules, such as nucleic acids.
Analysis of Fluorescence Lifetime of Protochlorophyllide and Chlorophyllide in Isolated Etioplast Membranes Measured from Multifrequency Cross‐correlation Phase Fluorometry
Authors: MySliwa‐Kurdziel Beata , Franck Fabrice , Strzatka Kazimierz
Published: January 2008

The fluorescence decays of protochlorophyllide (Pchlide) and of chlorophyllide (Chlide) in wheat etioplast membranes were analyzed using a multiexponential fluorescence decay model. Using different excitation wavelengths from 430 to 470 nm, we found that a triple‐exponential model at 14°C and a double‐exponential model at — 170°C were adequate to describe the Pchlide fluorescence decay. We discuss the origin of the three fluorescence lifetime components at 14°C on the basis of the dependence of their fractional intensities on the excitation wavelength and by correlating the fractional intensities with integrated fluorescence intensities of different Pchlide forms in steady‐state fluorescence spectra. The fluorescence decay of the main Pchlide form, photoactive Pchlide‐F657, is shown to have a complex character with a fast component of 0.25 ns and a slower component of about 2 ns. Two lifetime components of 2 ns and 5.5–6.0 ns are ascribed to the second photoactive form, Pchlide‐F645, and to nonphotoactive Pchlide forms, respectively. In etioplast membranes preilluminated by a short saturating light pulse, we found a single 5.0 ns component for Chlide‐F688 (the Chlide‐NADPH: protochlorophyllide oxidoreductase [PORJ‐NADP+complex) and an additional 1.6 ns component when the formation of Chlide‐F696 (the Chlide‐POR‐NADPH complex) was promoted by exogenous NADPH. From the fluorescence lifetime results we evaluated the quantum yield of the primary photoreaction by Chlide‐F696 as being 70%.
Photoprotective Effect of Black Tea Extracts Against UVB‐induced Phototoxicity in Skin
Authors: Zhao Jifu , Jin Xinho , Yaping E , Zheng Zai S. , Zhang Yu J. , Athar Mohammad , DeLeo Vincent A. , Mukhtar Hasan , Bickers David R. , Wang Zhi Y.
Published: January 2008

In previous studies, we showed that green tea and black tea extracts and their major polyphenolic constituents protect against UVB light‐induced carcinogenesis in murine skin. All of these studies required chronic administration of tea extracts or specific constituents either topically or orally. However, it is not known whether acute or subchronic administration of black tea extracts or constituents can ameliorate UVB‐induced early effects in skin. In the present study, cultured keratinocytes and mouse and human skin were employed to assess the effect of both oral and topical administration of standardized black tea extract (SBTE) and its two major polyphenolic subtractions namely BTF1 and BTF2 against UVB‐induced photodamage. In SKH‐1 hairless mice, topical application of SBTE (0.2 mg/cm2) prior to UVB exposure (180 mJ/cm2) resulted in 40% reduced incidence and 64% reduced severity of erythema and 50% reduction in skinfold thickness by day 6 when compared to nontreated UVB‐exposed animals. The SBTE was also effective in protecting against UVB‐induced erythema in human volunteers. Administration of SBTE 5 min after UVB irradiation was similarly effective in reducing UVB‐induced inflammation in both murine and human skin. The major polyphenolic subfractions, BTF1 and BTF2, were also effective in protecting in mouse skin. The SBTE subfractions inhibited UVB‐induced tyrosine phosphorylation of epidermal growth factor receptor (EGFR). The UVB irradiation of human epidermoid carcinoma cells resulted in 3.3‐fold induction of tyrosine phosphorylation of EGFR. Pretreatment with BTF1 and BTF2 reduced tyrosine phosphorylation of EGFR by 53% and 31%, respectively. The UVB‐mediated enhanced expression of the early response genes, c‐fos and c‐jun in human epidermal keratinocytes was reduced in a dose‐dependent manner by SBTE. Topical application of SBTE was also effective in reducing accumulation of c‐fos and p53 proteins by 82% and 78%, respectively, in UVB‐exposed mouse skin. These data provide evidence that constituents of black tea can abrogate UVB‐induced erythema and associated early events in murine and human skin.
5‐Aminolevulinic Acid Photosensitization of Dysplastic Barrett's Esophagus: A Pharmacokinetic Study
Authors: Ackroyd Roger , Brown Nicola , Vernon David , Roberts David , Stephenson Timothy , Marcus Stuart , Stoddard Christopher , Reed Malcolm
Published: January 2008

Photodynamic therapy (PDT) using 5‐aminolevulinic acid (ALA)‐induced protoporphyrin IX (PpIX) may have a role in the treatment of dysplastic Barrett's esophagus. Before ALA‐induced PDT can be used clinically, optimum treatment parameters must be established. In this study of 35 patients, the issues of drug dosage, time interval between drug and light delivery and side effects of oral ALA administration are addressed. Spectrofluoro‐metric analysis of tissue samples demonstrates that oral ALA administration induces porphyrin accumulation in esophageal tissues, with maximum levels at 4–6 h. High‐performance liquid chromatography confirms the identity of this porphyrin as PpIX, and fluorescence microscopy analysis demonstrates that it preferentially accumulates in the esophageal mucosa, rather than in the underlying stroma. Side effects of ALA administration included malaise, headache, photosensitivity, alopecia, transient derangement of liver function, nausea and vomiting. Fewer side effects and less hepatic toxicity was seen with 30 mg/kg than 50 mg/kg ALA. In conclusion, oral ALA administration induces preferential PpIX accumulation in the esophageal mucosa, with peak PpIX fluorescence noted at 4 h and minimal systemic toxicity at a dose of 30 mg/kg.
Solvent Dependence of the Fluorescence Lifetimes of Xanthene Dyes
Authors: Magde Douglas , Rojas Gail E. , Seybold Paul G.
Published: January 2008

Fluorescence lifetimes of Ave representative xanthene dye species‐the rhodamine B zwitterion (RB=), the rhoda‐mine B cation (RB+), the rhodamine 6G cation (R6G+), the rhodamine 101 zwitterion (R101) and the fluorescein dianion (F2‐)‐were measured in H2O, D2O and in a series of alcohol solvents ranging from methanol to octanol. The lifetimes of both RB= and RB+ increased markedly as the solvent was varied from water to octanol. In contrast, the lifetimes of R6G+ and R101± decreased slightly over the alcohol series and that of F2‐ increased only slightly in the same series. For all the dyes studied the fluorescence lifetimes observed in D2O were slightly longer than those in H2O. Possible causes for the variations observed are discussed.
Pharmacokinetics, Tissue Distribution and Photodynamic Therapy Efficacy of Liposomal‐Delivered Hypocrellin A, a Potential Photosensitizer for Tumor Therapy
Authors: Wang Zhi‐Jin , He Yu‐Ying , Huang Chao‐Guo , Huang Jin‐Sheng , Huang Ying‐Cai , An Jing‐Yi , Gu Ying , Jiang Li‐Jin
Published: January 2008

Hypocrellin A, from Hypocrella bambusae, is a novel photosensitizer of high singlet oxygen quantum yield for photodynamic therapy (PDT). Tissue distributions were studied in tumor‐bearing mice as a function of time following administration. The tumor model was S‐180 sarcoma transplanted into one hind leg of male Kunming mice; hypocrellin A (HA) was delivered to the mice by intravenous injection of 5 mg/kg of body weight as a suspension either as a unilamellar liposome or in dimethyl sulfoxide (DMSO)‐solubilized saline. The HA was isolated from several tissues and organs, as well as tumors and peritumoral muscles and skin. Quantitation was performed by a high‐performance liquid chromatographic technique with detection that utilizes the native fluorescence of HA. Independent of the delivery system, the dye was retained in tumors at higher concentrations than in normal tissues, except for kidney, liver, lung and spleen. The dye retention in tumors was high and was vehicle dependent. For the liposomal system, the maximal accumulation in tumor and maximal ratios of dye in tumor versus peritumoral muscle and skin occurred 12 h post‐injection; for the DMSO saline system, the maximal ratio occurred earlier, 6 h postadministration. Liposomal delivery improved the selective accumulation of the dye in tumor with higher maximal levels in tumor and higher ratios of tumor‐to‐muscle and tumor‐to‐skin. Levels of dye were very low or not detectable in the brain. The PDT efficacy of HA in the liposome and DMSO saline systems was determined by evaluating the tumor volume regression percent. The PDT efficacy of HA in liposomes was highest when light treatment was performed at 12 h postinjection, consistent with the highest retention of HA in tumors. Similarly, the maximal PDT efficacy in DMSO saline was attained at 6 h postinjection, the highest HA retention point in tumor. Moreover, the peak PDT efficacy of HA in liposomes was much higher than that of HA in DMSO saline and even hematoporphyrin mono‐methylether.
A Critical Role for Dermal Mast Cells in Cis‐Urocanic Acid‐induced Systemic Suppression of Contact Hypersensitivity Responses in Mice
Authors: Hart Prue H. , Grimbaldeston Michele A. , Swift Georgina J. , Hosszu Emma K. , Finlay‐Jones John J.
Published: January 2008

Many studies have implicated cu‐urocanic acid (cu‐UCA) in UVB‐induced immunomodulation. The strongest evidence came from studies in mice whereby a cis‐UCA antibody blocked UVB‐induced suppression of de‐layed‐type hypersensitivity responses. Furthermore, in several studies, the cis‐UCA antibody at least partially reversed UVB suppression of contact hypersensitivity responses. Previous reports suggested that cis‐UCA was immunomodulatory through its effects on keratinocytes, Langerhans cells, fibroblasts, T lymphocytes, natural killer cells and monocytes/macrophages. As dermal mast cells were recently demonstrated to be critical to UVB‐induced systemic suppression of certain delayed‐type and contact hypersensitivity responses, we investigated whether they were involved in the processes by which cu‐UCA was immunomodulatory. Not only was there a correlation between dermal mast cell prevalence and the degree of susceptibility of different strains of mice to the immunomodulatory effects of cis‐UCA, there was also a functional link. Mast cell‐depleted Wf/Wf mice were rendered susceptible to immunomodulation by cis‐UCA injected subcutaneously only after their dorsal skin had been reconstituted with bone marrow‐derived mast cell precursors. These studies suggest that mast cells are critical to the processes by which cis‐UCA suppresses systemic contact hypersensitivity responses to the hapten, trinitrochlorobenzene, in mice.
Bromohypericins Are Potent Photoactive Antiviral Agents
Authors: Hudson Jim B. , Delaey Els , de Witte Peter A.
Published: January 2008

Several hypericin derivatives, previously shown to have interesting light‐mediated biological activities, were evaluated for antiviral activities against herpes simplex virus and influenza virus. Three brominated hypericins, the di‐bromo‐ and tetrabromo‐derivatives and the natural compound gymnochrome B were all very active against both viruses, particularly herpes simplex virus, although light was required in all cases for maximum activity. The di‐bromohypericin was the most potent, under standard assay conditions, gymnochrome B was approximately as active as hypericin itself and tetrabromohypericin significantly less so. Surprisingly, hexamethylhypericin, which is known to have potent anti‐protein kinase (PK) C activity, as well as anticell proliferation properties, showed no antiviral activity at all. The compounds were also evaluated in different serum concentrations. All the active compounds were inhibited by increasing concentrations of serum, but to different degrees, such that their relative antiviral potencies changed to some extent Thus, in summary, there was no correlation between antiviral and anti‐PK or anticellular activities, and consequently it is not possible at present to define those structural features of hypericin‐type molecules that are required for their various biological activities.
Photodynamic Effectiveness and Vasoconstriction in Hairless Mouse Skin after Topical 5‐Aminolevulinic Acid and Single‐ or Two‐fold Illumination
Authors: de Veen Nynke , Hebeda Konnie M. , de Bruijn Henriëtte S. , Star Willem M.
Published: January 2008

Several options were investigated to increase the efficacy of photodynamic therapy (PDT) using protoporphyrin IX (PpIX) induced by topically applied 5‐aminolevulinic acid (ALA). Hairless mice with normal skin or UVB‐light‐induced skin changes were used as a model. In the first part of the study animals were illuminated immediately (t = 4) or 6 h (t = 10, PpIX fluorescence maximum) after the end of a 4 h ALA application. A total incident light fluence of 100 J/cm2 (514.5 nm) was delivered at a fluence rate of 100 or 50 mW/cm2. The PDT‐induced damage to normal skin was more severe after treatment at t = 10 than at t = 4. Illumination at 50 mW/ cm2 caused significantly more visible damage than the same light fluence given at 100 mW/cm2. For UVB‐illu‐minated skin, different intervals or fluence rates made no significant difference in the severity of damage, although some qualitative differences occurred. In situ fluence rate measurements during PDT indicated vasoconstriction almost immediately after the start of the illumination. A fluorescein exclusion assay after PDT demonstrated vasoconstriction that was more pronounced in UVB‐treated skin than in normal skin. The second part of the study examined the effect of two illuminations. The first illumination bleaches the PpIX fluorescence. At the start of the second illumination, new PpIX had been formed. Light of 514.5 nm was delivered at 100 mW/cm2 to a total incident light fluence of 200 J/cm2 at t = 4 (single illumination) or 100 J/cm2 at t = 4 plus 100 J/cm2 at t = 10. There was no visual difference in skin damage between 100 and 200 J/cm2 single illumination. Two‐fold illumination (100 + 100 J/cm2) caused significantly more skin damage, indicating a potentially successful option for increasing the efficacy of topical ALA‐PDT.
Phosphorylation of Sp1 in Response to DNA Damage by Ataxia Telangiectasia-Mutated Kinase
Authors: Olofsson Beatrix A. , Kelly Crystal M. , Kim Jiyoon , Hornsby Stephen M. , Azizkhan-Clifford Jane
Published: January 2008

Sp1, a transcription factor that regulates expression of a wide array of essential genes, contains two SQ/TQ cluster domains, which are characteristic of ATM kinase substrates. ATM substrates are transducers and effectors of the DNA damage response, which involves sensing damage, checkpoint activation, DNA repair, and/or apoptosis. A role for Sp1 in the DNA damage response is supported by our findings: Activation of ATM induces Sp1 phosphorylation with kinetics similar to H2AX; inhibition of ATM activity blocks Sp1 phosphorylation; depletion of Sp1 sensitizes cells to DNA damage and increases the frequency of double strand breaks. We have identified serine 101 as a critical site phosphorylated by ATM; Sp1 with serine 101 mutated to alanine (S101A) is not significantly phosphorylated in response to damage and cannot restore increased sensitivity to DNA damage of cells depleted of Sp1. Together, these data show that Sp1 is a novel ATM substrate that plays a role in the cellular response to DNA damage. (Mol Cancer Res 2007;5(12):1319–30)
The Topology of the Protein Network Influences the Dynamics of Gene Order: From Systems Biology to a Systemic Understanding of Evolution
Authors: Knibbe Carole , Fayard Jean-Michel , Beslon Guillaume
Published: January 2008

Systems biology invites us to consider the dynamic interactions between the components of a living cell. Here, by evolving artificial organisms whose genomes encode protein networks, we show that a coupling emerges at the evolutionary time scale between the protein network and the structure of the genome. Gene order is more stable when the protein network is more densely connected, which most likely results from a long-term selection for mutational robustness. Understanding evolving organisms thus requires a systemic approach, taking into account the functional interactions between gene products, but also the global relationships between the genome and the proteome at the evolutionary time scale.
Innovation, NCLB, and the Fear Factor
Authors: Schoen LaTefy , Fusarelli Lance D.
Published: January 2008

This article explores the impact of the No Child Left Behind Act (NCLB) on the behavior of teachers and school leaders, specifically the centralizing, standardizing tendencies of the legislation, and juxtaposes their reactions to the types of teaching and leadership required to lead 21st-century schools. The authors argue that the isomorphic behavioral responses to NCLB conflict with the pedagogical and leadership behaviors of the 21st-century schools movement. The authors conclude that unless modifications are made to the legislation, teachers and school leaders are unlikely to exhibit or promote the types of pedagogical skills, knowledge, or leadership envisioned by advocates of 21st-century schools.
The Culture of Fear and the Politics of Education
Authors: Ginsberg Rick , Lyche Leif Frederick
Published: January 2008

American public education has historically been considered a great success. Since the release of the landmark 1983 federal report, A Nation at Risk, concerns about many aspects of American education have been highly publicized. Although the actual extent of the degree of problems facing public education is debated, this article argues that the state of education has become part of a “culture of fear” gripping many aspects of society. The research examines polling data and newspaper stories on selected educational topics for four newspapers since 1980 and shows that both the number of stories on these topics and negative tone of the stories have increased, while polling data suggest that public perceptions about education have remained stable. At the same time, however, issues of quality have emerged as concerns. The implications of these findings suggest a need for further study of the current nature of the politics of education.
School Safety
Authors: Lindle Jane Clark
Published: January 2008

The image of schooling tends to be benign, lulling parents and guardians into an assumption of safety for at least 6 hours each weekday. The complement to safety as an imagined state of schooling contains incidents of school violence and tragedy that feed communities' and parents' primeval fears about the well being of their children. The consequences of imagined safety, along with panic resulting from incidents of school violence or other lapses in school safety, yield school policies and rules that, perversely, may exacerbate community fears. Under the 2001 federal law known as No Child Left Behind (NCLB), the consequences of a public accounting for school safety may have generated more opportunities for public fear and panic as opposed to increasing conditions for school safety and security. The article concludes with strategies, rather than the blunt legislative approach to policies, for mediating public fears by ensuring genuine school safety.
Fearful Reformers
Authors: Cibulka James G. , Myers Nathan
Published: January 2008

This research article analyzes the ways that the Christian right uses fear as an instrument in the politics of education. The main source of data for this analysis draws from source-protected interviews with directors in state-level Christian right organizations. A semistructured, elite interviewing approach was used. The authors reframe the debate in the scholarly literature over whether fear is used disingenuously or whether it has a rational basis in the belief systems of the Christian right. Instead, the authors address how the Christian right's political power became institutionalized in recent decades through interest groups, policy entrepreneurs, advocacy coalitions, and national political party alliances. Finally, the article evaluates the role that fear continues to play as both a belief and a tactic as the Christian right has moved into the political mainstream.
Fear and Privatization
Authors: Cooper Bruce S. , Randall E. Vance
Published: January 2008

Supporters of public education fear attempts to privatize schools, while the private sector has always struggled against the monopolistic power of the public schools that educates almost 90% of all K-12 students. This trepidation has recently been intensified by the creation of a “third sector” that includes charter schools, voucher programs, and the increased diversity of private education. This article looks at the dynamics of fear as shaped by increased competition among public, private, and privatized schools. In fact, both public schools and their private school counterparts, fear privatization of education because it draws students and resources away from traditional schools. And recently, the opening of new “religious charter schools” has crossed the lines between church and state, and between private and public education. Thus, the politics of education have become somewhat more confused and unnerving as the distinctions between public and private education are virtually disappearing.
Content Follows Form: Preservation via Systems Design
Authors: Chapman Stephen
Published: January 2008

The human-perceived content of any digital object is an artifact of systems, not an amalgamation of fixed physical attributes. Many of these objects are designed to have multiple renderings to optimize content for specific tasks, such as searching, sorting, analyzing, or reading. Using digital technology either to reproduce historic materials or to preserve original digital objects requires a definition of information integrity that accommodates function as well as appearance. The choice of encoding is critical to enable specified functionality, but the choice of repository is likely to be
Raising Lazarus: Revitalizing an In-House Microfilming Operation
Authors: Helmer Normandy
Published: January 2008

The Oregon Newspaper Project (ONP) was established in 1952 as a joint venture between the Oregon Newspaper Publishers Association and the University of Oregon Library. Filming began the following year and has continued uninterrupted for 49 years. More than 15,000 reels of film have been produced, capturing one of the most complete archives of state newspaper publication in the nation.
Retinocollicular Synapse Maturation and Plasticity Are Regulated by Correlated Retinal Waves
Authors: Shah Ruchir D. , Crair Michael C.
Published: January 2008

During development, spontaneous retinal waves are thought to provide an instructive signal for retinotopic map formation in the superior colliculus. In mice lacking the β2 subunit of nicotinic ACh receptors (β2−/−), correlated retinal waves are absent during the first postnatal week, but return during the second postnatal week. In control retinocollicular synapses,in vitroanalysis reveals that AMPA/NMDA ratios and AMPA quantal amplitudes increase during the first postnatal week while the prevalence of silent synapses decreases. In age-matched β2−/−mice, however, these parameters remain unchanged through the first postnatal week in the absence of retinal waves, but quickly mature to control levels by the end of the second week, suggesting that the delayed onset of correlated waves is able to drive synapse maturation. To examine whether such a mechanistic relationship exists, we applied a “burst-based” plasticity protocol that mimics coincident activity during retinal waves. We find that this pattern of activation is indeed capable of inducing synaptic strengthening [long-term potentiation (LTP)] on average across genotypes early in the first postnatal week [postnatal day 3 (P3) to P4] and, interestingly, that the capacity for LTP at the end of the first week (P6–P7) is significantly greater in immature β2−/−synapses than in mature control synapses. Together, our results suggest that retinal waves drive retinocollicular synapse maturation through a learning rule that is physiologically relevant to natural wave statistics and that these synaptic changes may serve an instructive role during retinotopic map refinement.
Establishment of a Scaffold for Orientation Maps in Primary Visual Cortex of Higher Mammals
Authors: Grabska-Barwińska Agnieszka , von der Malsburg Christoph
Published: January 2008

In higher mammals, environmentally driven patterns of neural activity do not play a role in the establishment of orientation specificity and maps. It has been proposed that specific long-range interactions provide the scaffold for developing orientation maps. Our model aims at explaining how such a scaffold could develop in the first place. Broad spontaneous activity waves and locally evoked spatially periodic response pattern are used. The model is discussed in relation to biological evidence, and experiments to test the model are proposed. We show that reliable orientation specificity cannot be a result of haphazard cortical wiring, as has been proposed.
INFANT-VENTILATOR INTERACTION CAN AFFECT CEREBRAL BLOOD FLOW IN PRETERM INFANTS: COMPARISON BETWEEN 2 MODES
Authors: El-Moneim Ehab Saoud Abd , Hans-Otto Fuerste , Markus Krueger , Elmagd Ali Abou , Brandis Matthias , Schulte-Moenting Jürgen , Hentschel Roland
Published: January 2008

INTRODUCTION: Disturbance of cerebral blood flow (CBF) has been associated with neonatal brain injury. Because CBF is greatly influenced by mechanical ventilation, it is important to consider the effect of ventilation mode on CBF. We have shown that pressure-support ventilation combined with volume-guarantee mode (PSV-VG) would lower ventilation pressures and improve infant-ventilator synchrony when compared with synchronized intermittent mandatory ventilation (SIMV).

OBJECTIVE: Our aim was to compare the effect of PSV-VG and SIMV on CBF.

METHODS: To study an on/off effect, 33 preterm infants (mean gestational age: 26.6 ± 2.2 weeks) were switched from SIMV to PSV-VG and back again to SIMV. By using Doppler techniques, anterior cerebral artery pulsatility index (PIaca), superior vena cava flow (SVCF), and aortic minute distance (MDao) were measured in each phase. Infants were grouped according to patency of ductus arteriosus.

RESULTS: When the duct was closed, the PIaca decreased significantly (P = .002), which indicates higher CBF, SVCF increased by 20.1% ± 7.4% (P = .01), and MDao increased by 14.6% ± 4.1% (P = .007) during PSV-VG. In the group with patent ductus arteriosus, although MDao decreased by 10.5% ± 4.4% (P = .04) during PSV-VG, the PIaca and SVCF remained constant. We also observed noticeable changes in the pattern of SVCF Doppler waveform as infant-ventilator interaction changed with switching the ventilation mode. Such pattern changes are described here for the first time.

CONCLUSIONS: The interaction between the ventilation mode, the shunt across the duct, and probably CBF autoregulation determines the effect of mechanical ventilation on CBF. Studying the SVCF Doppler waveform pattern may be a useful tool for assessing ventilator-patient interaction.
AMNIOTIC FLUID TRANSFORMING GROWTH FACTOR β AND THE DEVELOPMENT OF NEONATAL CHRONIC LUNG DISEASE
Authors: Ichiba Hiroyuki , Saito Mika , Yamano Tsunekazu
Published: January 2008

INTRODUCTION: Chorioamnionitis can initiate fetal lung injury and result in neonatal chronic lung disease (CLD). Although neonates with CLD have higher amniotic fluid concentrations of proinflammatory cytokines, overexpression of transforming growth factor β (TGF-β) also seems to be important in the pathogenesis of neonatal CLD.

OBJECTIVE: Our goal was to investigate how TGF-β is related to fetal lung injury induced by chorioamnionitis.

METHODS: Forty-four amniotic fluid samples were obtained at delivery from preterm infants (median gestational age: 28 weeks; median birth weight: 908 g). TGF-β and interleukin 6 (IL-6) concentrations in amniotic fluid were measured with enzyme-linked immunosorbent assays.

RESULTS: TGF-β concentration in amniotic fluid correlated with IL-6 concentration (P < .0001). Both TGF-β and IL-6 concentrations in amniotic fluid increased with increasing histologic severity of chorioamnionitis (each P < .0001). Coexisting presence of neonatal CLD and histologic chorioamnionitis was associated with significantly higher amniotic fluid TGF-β and IL-6 concentrations than presence of neonatal CLD without histologic chorioamnionitis or absence of both (mean TGF-β level: 454.3 vs 119.2 vs 151.8 pg/mL [P < .0001]; mean IL-6 level: 5.14 vs 0.99 vs 1.64 ng/mL [P = .0005]). Both TGF-β and IL-6 concentrations in amniotic fluid correlated with duration of neonates' need for oxygen administration (each P < .0001).

CONCLUSIONS: Amniotic fluid TGF-β may be important in chorioamnionitis-induced fetal lung injury that results in neonatal CLD.
INFANT OUTCOME AFTER ANTENATAL STEROIDS IN PRETERM PREGNANCIES WITH ABSENT UMBILICAL END-DIASTOLIC FLOW
Authors: Murila Florence , Feng Susan , Robertson Michael , Yu Victor , Wallace Euan
Published: January 2008

INTRODUCTION: Absence of the end-diastolic flow (EDF) is associated with adverse neonatal outcome. Administration of β-methasone to women with a pregnancy complicated by absent EDF is associated with the transient return of EDF in up to 70% of cases.

OBJECTIVE: We aimed to compare the hospital outcome of preterm infants for whom the absent EDF returned after antenatal administration of β-methasone with those for whom the absent EDF did not return.

METHODS: At Monash Medical Center, 80 pregnant women with absent EDF were given 2 intramuscular 11.4-mg doses of β-methasone 24 hours apart. In the majority of pregnancies, EDF returned after β-methasone treatment. The preterm infants born to these 80 pregnant women had their hospital outcome ascertained retrospectively. Statistical analysis was performed by using the χ2 and Mann-Whitney rank-sum tests.

RESULTS: The 51 infants for whom the EDF returned were compared with the 29 for whom the EDF did not return. There were no significant differences in their gestational age, birth weight, or resuscitation and ventilation needs. The former group was less acidotic at birth (mean pH: 7.4 vs 7.3 [P < .05]; and mean base excess: −3 vs −5 mmol/L [P < .05]). There was no significant difference in the incidence of respiratory disease, intraventricular hemorrhage, necrotizing enterocolitis, and mortality rates.

CONCLUSIONS: Preterm infants born after return of an absent EDF after the administration of antenatal β-methasone were less acidotic at birth, but their hospital morbidity and mortality rates were not significantly improved compared with those for whom the absent EDF did not return.
PERIPHERAL BLOOD COUNT FOR DENGUE SEVERITY PREDICTION: A PROSPECTIVE STUDY IN THAI CHILDREN
Authors: Eu-Ahsunthornwattana Nanthakorn , Eu-ahsunthornwattana Jakris , Thisyakorn Usa
Published: January 2008

INTRODUCTION: Dengue viral infection has a wide range of severity levels and requires different levels of medical attention. Early severity prediction using clinical features is difficult. Certain lymphocytic subtypes can be used to predict severity; we postulate that peripheral blood counts can also predict severity, which would be more useful in smaller rural hospitals.

OBJECTIVE: We aimed to compare the peripheral blood counts between patients with mild dengue infection and those with severe dengue infection and identify simple yet sensitive early severity predictors.

METHODS: We enrolled 91 patients with serologically confirmed dengue infection who were admitted to King Chulalongkorn Memorial Hospital. Their leukocytic counts on admission were compared. Potential predictors were identified by using receiver-operating-characteristic analysis.

RESULTS: Compared with patients with mild infection, those with severe infection (dengue hemorrhagic fever grade II or worse) had a higher leukocyte count (3580 vs 3050 cells per μL; P = .04), and fewer had leukopenia on admission (70% vs 89%; P = .03). They also had a lower percentage of “typical” lymphocytes (24% vs 40%; P = .02). Two predictors were identified; either one classified ∼19% of all admitted patients as being at low risk. Typical lymphocyte counts of <40% excluded patients with mild disease with 89% sensitivity and 24% specificity (negative predictive value: 77%; positive predictive value: 45%). A combination of parameters [(white blood cells per μL) + 470 × (% typical lymphocytes) + 5 × (atypical lymphocytes per μL) ≥−14 950] improved the sensitivity and specificity to 92% and 26% (negative predictive value: 82%; positive predictive value: 46%).

CONCLUSIONS: The absence of leukopenia and a low percentage of typical lymphocytes predict severe dengue illness. Simple hematologic parameters may be used to reduce unnecessary admissions of patients with suspected dengue infection in the absence of more sophisticated predictors.
RE-TREATMENT AND RISK FACTORS OF REFRACTORY KAWASAKI DISEASE
Authors: Du Zhong-Dong , Zhao Di , Du Junbao
Published: January 2008

OBJECTIVE: The objective of this study was to evaluate the incidence and risk factors of children with refractory Kawasaki disease (KD).

METHODS: All children with KD were analyzed in Beijing from 2000 through 2004. Risk factors were analyzed by logistic regression. Refractory KD was defined as persistent fever of ≥38.5°C 36 hours after initial intravenous immunoglobulin (IVIg) treatment.

RESULTS: A total of 1052 patients (aged 1 month to 13.8 years) with IVIg treatment were included; of them, 135 did not respond to IVIg treatment, with an incidence of 12.8%. Refractory KD occurred more frequently in children who received 1 g/kg per day IVIg for 2 days (20.9%) than in those who received a single dose of 2 g/kg (9.9%) or 400 to 600 mg/kg per day for 4 days (8.7%). Logistic regression revealed that erythrocyte sedimentation rate, alanine aminotransferase, white blood cell count, serum albumin, time from onset to IVIg treatment, and IVIg dosage were independent risk factors for refractory KD. Children with refractory KD were re-treated: 8 received 2 g/kg IVIg, with 5 (62.5%) responding; 114 received 1 g/kg IVIg, with 35 (30.7%) responding; and 11 received 400 to 600 mg/kg IVIg, with (9.1%) responding. In addition, 2 received corticosteroids, with 2 responding.

CONCLUSIONS: The incidence of refractory KD in Beijing is 12.8%. A 2-g/kg dose of IVIg is probably the best re-treatment option for refractory KD.
ROLE OF THROMBOMODULIN IN DETECTION OF ENDOTHELIAL CELL DESTRUCTION AFTER INFECTION WITH FALCIPARUM AND TERTIAN MALARIA
Authors: Mantik Max , Rampengan Tonny , Kilis Mariane , Tuda Josef
Published: January 2008

INTRODUCTION: Thrombomodulin is an endothelial cell receptor for thrombin. In tropical and tertian malaria, thrombomodulin is secreted after endothelial cell destruction after infections with Plasmodium falciparum or Plasmodium vivax.

OBJECTIVE: Our goal was to investigate whether thrombomodulin levels can be used to detect the endothelial cell destruction after tropical or tertian malaria and whether thrombomodulin is related to the severity of tropical malaria.

METHODS: This was a cross-sectional observational analytical study conducted in 5 hospitals in north Sulawesi, Indonesia, from June to September 2006, in patients aged 2 to 13 years with tropical or tertian malaria. Thrombomodulin levels were determined with an enzyme-linked immunosorbent assay using a thrombomodulin kit (Fujirebio Diagnostics, Inc, Malvern, PA). Data were analyzed by independent t test and Spearman rank correlation coefficient.

RESULTS: For 30 patients with tropical malaria (thrombomodulin level: 0.060–0.180 FU/mL) and 2 patients with tertian malaria (thrombomodulin level: 0.068–0.075 FU/mL), there was a significant difference in t-test results between tropical and tertian malaria (P = .044). For 11 patients with severe malaria (thrombomodulin level: 0.086–0.162 FU/mL), there was also a very significant difference in t-test results for complicated and uncomplicated tropical malaria (P = .009). The Spearman rank test showed significant positive correlation between thrombomodulin and parasitemia levels (rs = 0.686; P = .001).

CONCLUSIONS: Thrombomodulin levels can be used to detect endothelial cell destruction in malaria; the thrombomodulin level in tropical malaria was found to be higher than that of tertian malaria. Thrombomodulin levels were very significantly different in complicated and uncomplicated tropical malaria and also correlated significantly with the degree of parasitemia.
USING NONSTEROIDAL ANTIINFLAMMATORY DRUGS IN VOLUME-DEPLETED CHILDREN CAN PRECIPITATE ACUTE RENAL FAILURE
Authors: John Cheri Mathews , Saroha Vivek , Jones Caroline
Published: January 2008

INTRODUCTION: Nonsteroidal antiinflammatory drugs (NSAIDs) are ever increasing in popularity in hospital medicine and general practice and are readily available over-the-counter.

OBJECTIVE: Our goal was to illustrate the need to be aware of the effect of NSAIDs on dehydrated patients.

PATHOGENESIS: The risk of renal toxicity is increased in situations in which there is a stimulation of the renin-angiotensin system such as volume depletion. In these conditions, circulating vasoconstrictors are released, maintaining vascular resistance and blood pressure at the potential expense of regional organ blood flow. To maintain renal blood flow, counter-regulatory renal prostaglandins are released that counteract vasoconstrictors and normalize renal blood flow. NSAIDs blunt this counter-regulatory response and intensify the renal vasoconstriction, which leads to acute renal failure. In Table 1 we report 4 children with mild dehydration who developed acute renal failure after the use of therapeutic doses of NSAIDs in a children's hospital.

CONCLUSIONS: We recommend that NSAIDs should be avoided in children with actual or potential intravascular volume depletion. Although we have not proven cause and effect, additional research is needed to define the true risk of the potential renal complications of using NSAIDs in patients who are at risk of dehydration.

NOTE: The cases of the 4 children described in this report have been published elsewhere (John CM, Shukla R, Jones CA. Using NSAID in volume depleted children can precipitate acute renal failure. Arch Dis Child. 2007;92:524–526).

TABLE 1.Acute Renal Failure in 4 Children After Use of NSAIDsPatient No.1234Age, y1371413GenderMaleMaleMaleFemaleUnderlying pathologyCraniopharyngioma diabetes insipidusJuvenile idiopathic arthritis; fasted for surgeryJuvenile idiopathic arthritis with vomitingRelapse of Crohn diseaseNSAIDDiclofenac sodiumIndomethacin diclofenac sodiumDiclofenac sodiumDiclofenac sodiumHighest urea level, mmol urea/L10.712.910.722Highest creatinine level, μmol/L226146376629Normalization, d533Permanent impairment
EFFECT OF BCG VACCINATION ON SPLENIC DENDRITIC CELL DEVELOPMENT IN NEONATAL BALB/C MICE
Authors: Enmei Liu , Chunhua Liu , Yun He , Wei Liu , Xin Li , Liping Jiang , Xiqiang Yang
Published: January 2008

INTRODUCTION: As an immunoregulator, Mycobacterium BCG has the potential to be applied in allergic disease such as asthma prevention in clinic. Previous studies showed that neonatal BCG vaccination promoted mouse splenic T helper 1 development.

OBJECTIVE: The objective of this study was to investigate further the impact of BCG vaccination on dendritic cell (DC) development in neonatal mice.

METHODS: Neonatal and adult BALB/C mice were divided into 2 groups: the control group and the BCG-treated group in which BALB/C mice were inoculated with 1 × 105 colony-forming units of BCG intraperitoneally. After 4 weeks, splenic cells were isolated and co-stimulatory molecules and major histocompatibility complex molecules were analyzed by flow cytometry on CD11c-positive cells.

RESULTS: CD11c+CD8α+ and CD11c+CD8α− DCs were found in spleen cells of BALB/C mice. In comparison with the control group, the percentage of CD8α− DCs was significantly decreased (45.00 ± 14.14 vs 67.00 ± 8.27) and that of CD8α+ DCs was strikingly increased (55.00 ± 14.14 vs 33.00 ± 8.27) in BCG-treated neonatal mice. In contrast, the percentage of CD8α− DCs markedly increased from 57% to 70% and that of CD8α+ DCs noticeably decreased from 43% to 30% in adult mice that were vaccinated. BCG vaccination upregulated the expression of co-stimulatory molecules on DC in adult and neonatal mice.

CONCLUSIONS: Our results indicate that development of T cells was induced by BCG vaccination through an effect on DC differentiation and maturation in BALB/C mice, possibly not only by DC phenotype but also by cytokines.
EXPRESSION CHANGE OF AQUAPORIN 1 IN HYPEROXIC LUNG INJURY
Authors: Xu Feng , Hao Jie , Tan Liping
Published: January 2008

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a disease that is caused by prolonged high-concentration oxygen therapy, and its typical pathologic character is edema of pulmonary alveolus. Aquaporins play an important role in the fluid transition.

OBJECTIVE: The objective of this study was to examine the expression change of aquaporin 1 (AQP1) in hyperoxia-induced lung injury and the mechanism of action in lung edema.

METHODS: Thirty-two juvenile Wistar rats were randomly divided into breathing room air (n = 8) and hyperoxia exposure (O2 > 95%; n = 8 at 3, 7, and 14 days, respectively). The distribution of AQP1 in the lung tissues and its mRNA expressions were detected by immunohistochemistry and reverse-transcription polymerase chain reaction.

RESULTS: Light microscopic findings in the hyperoxia group included edema, hemorrhage, and extensive inflammatory cells. The lung wet/dry ratio, the protein content in bronchoalveolar lavage fluid, and the lung leak index in the hyperoxia group were significantly higher than those in room air group. The expression of AQP1 mRNA in the lungs was significantly decreased at 3 days of hyperoxia exposure, minimized at 7 days, and increased from 14 days. Immunohistochemistry for AQP1 was seen primarily in microvascular endothelia cells around bronchus and alveolus and interstitial cells; the positive regions were similar between the room air group and the hyperoxia group, AQP1 protein expression in the lungs was significantly decreased at 3 days of hyperoxia exposure, minimized at 7 days, but increased at 14 days. The dynamic changes of AQP1 protein level coincided with the changes of AQP1 mRNA expression.

CONCLUSIONS: Hyperoxic lung injury may induce regulative imbalance of aquaporin expression. It may be 1 of the reasons for lung edema caused by hyperoxic lung injury.