bluuebunny/crossref_metadata_2025_split huggingface dataset:
UVB Induces IL‐12 Transcription in Human Keratinocytes in vivo and in vitro
Authors: Enk Claes D. , Mahanty Siddhartha , Blauvelt Andrew , Katz Stephen I. 
Published: January 2008

ABSTRACTHuman epidermal cells produce a wide range of cytokines, including those characteristic of Th2‐like responses such as interleukin (IL)‐4 and IL‐10. As well, keratinocytes have recently been shown to produce Th1‐like cytokines such as IL‐12. Exposure to UVB has profound effects on the skin and systemic immune system, which is in part mediated by secretion of tumor necrosis factor (TNF)‐α by epidermal cells. Because IL‐12 induces production of TNF‐α by certain cells of the immune system, we sought to determine whether UVB is an inducer of IL‐12 gene expression in epidermal cells. Human epidermal cells were exposed to UVB radiation in vivo, isolated by suction blister technique and trypsinization and transcription of the IL‐12 p35 and p40 chains was examined by RT‐PCR. We found the p35 chain of IL‐12 to be constitutively expressed and the p40 chain inducible by UVB irradiation. Because epidermis consists of a heterogenous cell population with distinct cytokine repertoires, we sought to determine the cellular source of the IL‐12 message after UVB exposure. After depleting UVB‐exposed epidermal cells for DR+ cells, no reduction in the IL‐12 activity was detected, suggesting that keratinocytes are a source of IL‐12 transcripts in UVB‐exposed human epidermis. This was supported by the up‐regulation of IL‐12 p40 transcripts in UV‐irradiated cultured keratinocytes that were devoid of DR+ cells. Up‐regulation of IL‐12 p40 gene expression by UVB as demonstrated here, taken together with the finding that keratinocytes also up‐regulate IL‐10 transcription, suggests that there is a complex interplay between Th1‐and Th2‐like epidermisderived cytokines following exposure to UVB.
Photodynamic Imaging of a Rat Pancreatic Cancer with Pheophorbide a
Authors: Keller P. , Sowinska M. , Tassetti V. , Heisel F. , Hajri A. , Evrard S. , Miehe J. A. , Marescaux J. , Aprahamian M. 
Published: January 2008

ABSTRACTLaser‐induced fluorescence of pheophorbide a (Ph‐a) was used for in vitro photodynamic imaging (PDI) of a rat pancreatic acinar tumor. A 400 nm excitation induced a 470 nm autofluorescence and a 678 nm dye fluorescence in tumors and their surrounding pancreas 24 h after a 9 mg kg−1 body weight Ph‐a intravenous administration. With lower intensities in these blood‐rich tumors than in pancreas, Ph‐a fluorescence signals are unable to provide tumor images. A dimensionless function (the ratio of Ph‐a fluorescence by autofluorescence, called Rt for the tumor and Rp for the pancreas) was used for fluorescence contrast calculation (C = Rt/Rp) between six tumors and their paired pancreas. Among five available laser excitation wavelengths, only the 355 nm excitation gave a distinctive contrast (C = 1.5). The PDI of six intrapancreatic tumors and their intraperitoneal metastasis and of two control normal pancreas was thus performed ex vivo using a 355 nm excitation source delivered by a tripled Nd: YAG laser and a charged‐coupled device camera. Fluorescence images were recorded at 680 nm (dye), 640 nm (background) and 470 nm (autofluorescence) through three corresponding 10 nm width bandpass filters. Computed division for each pixel of Ph‐a fluorescence values by autofluorescence generated false color image. In this way, contrasted tumor images were obtained. But in five out of six animals false‐positive images were present due to an autofluorescence decrease in some normal pancreatic areas. A 470 nm autofluorescence imaging on the same tumors gave in all cases false‐positive image and false‐negative in half of the cases. These observations suggest that autofluorescence alone is unable to achieve accurate PDI of pancreatic carcinoma and that using Ph‐a as a PDI dye needs strong improvements.
Ultraviolet Spectral Energy Differences Affect the Ability of Sunscreen Lotions to Prevent Ultraviolet‐Radiation‐Induced Immunosuppression*
Authors: Robertst Lee K. , Beasley Donathan G. , Learn Douglas B. , Giddens Lori D. , Beard John , StanfieW Joseph W. 
Published: January 2008

ABSTRACTAcute exposure to UV radiation causes immunosuppression of contact hypersensitivity (CH) responses. Past studies conducted with unfiltered sunlamps emitting nonsolar spectrum UV power (wavelengths below 295 nm) or using excessive UV doses have suggested sunscreens may not prevent UV‐induced immunosuppression in mice. This study was thus designed to evaluate critically the effects of different UV energy spectra on the immune protection capacity of sunscreen lotions. Minimum immune suppression doses (MISD), i.e. the lowest UV dose to cause~50% suppression of the CH response to dinitrofluorobenzene in C3H mice, were established for three artificial UV sources. The MISD for each UV source was 0.25 kJ/m2 for unfiltered FS20 sunlamps (FS), 0.90 kJ/m2 for Kodacel‐filtered FS20 sunlamps (KFS), which do not emit UV power at wavelengths <290 nm, and 1.35 kJ/m2 for a 1000 W filtered xenon arc lamp solar simulator. Using MISD as baseline, sunscreens with labeled sun protection factors (SPF) of 4, 8, 15 and 30 were tested with each UV source to establish their relative immune protection factors. The immune protection factor of each sunscreen exceeded its labeled SPF in tests conducted with the solar simulator, which has a UV power spectrum (295–400 nm) similar to that of sunlight. Conversely, sunscreen immune protection factors were significantly less than the labeled SPF in tests conducted with FS and KFS. Comparison of the immunosuppression effectiveness spectra showed that relatively small amounts of nonsolar spectrum UV energy, i.e. UVC (200–290 nm) and/or shorter wavelength UVB (between 290 and 295 nm), produced by FS and KFS contributes significantly to the induction of immunosuppression. For example, 36.3% and 3.5% of the total immunosuppressive UV energy from FS and KFS, respectively, lies below 295 nm. Sunscreen absorption spectra showed that transmission of immunosuppressive UV energy below 295 nm for FS was at least eight‐fold higher than that for KFS. Compared to the solar simulator UV spectrum the transmission of nonsolar immunosuppressive UV energy through sunscreens was >15‐fold higher for FS and ≥1.5‐fold higher for KFS. These data demonstrate that relevant evaluations of sunscreen immune protection can only be obtained when tests are conducted with UV sources that produce UV power spectra similar to that of sunlight and UV doses are employed that are based on established MISD.
Distribution and Excretion of Radiolabeled Temoporfin in a Murine Tumor Model
Authors: Whelpton Robin , Michael‐Titus Adina T. , Jamdar Ravi P. , Abdillahi Kaltun , Grahn Michael F. 
Published: January 2008

ABSTRACTThe biodistribution and excretion of temoporfin (tetra[m‐hydroxyphenyl]chlorin, m‐THPC), a recently developed photosensitizer, was investigated in BALB/c mice. [14C]temoporfin was administered intravenously (0.73 μmol/kg) to tumor‐free mice or to mice implanted with the Colo 26 colorectal carcinoma. Blood, tissue and fecal samples were collected for 35 days and 10 days postdose from tumor‐free mice and tumor‐bearing mice, respectively. Blood concentrations fell rapidly such that at later time points they were indistinguishable from background counts. Tumor concentrations rose to a peak of 0.34 μg temoporfin equivalents/mL at 2 days and then declined in parallel (log plot) with the blood concentrations. Tumor : tissue ratios at 2 days for skin, adipose tissue and skeletal muscle underlying the tumor were 1.5, 2.3 and 3.8, respectively. By 4 days the corresponding values were 1.6, 3.4 and 4.0. Nearly 40% of the administered radioactivity was excreted in the feces in the first 24 h and more than 80% had been excreted by 20 days. Less than 0.2 % of the dose was recovered from the urine. An elimination half‐life of 10–12 days was calculated from the excretion data.
On the Roles of Urocanic Acid in Photoimmunosuppression: Attempted Photorepair of Urocanic Acid‐DNA Cyclobutane Adducts with DNA Photolyase
Authors: Terrian Deborah L. , Kuhll C. Nicole , Tessman Irwin , Morrison Harry 
Published: January 2008

ABSTRACTIt has been reported that UV‐induced immunosuppres‐sion can be reversed by photoreactivation or exposure to T4 endonuclease V, two treatments that can repair cyclobutane pyrimidine dimers. These observations, together with the known role of urocanic acid (UA) in UV‐induced immune suppression, prompted us to study the ability of DNA photolyase to repair UA‐DNA cyclobutane photoadducts in single‐stranded calf thymus DNA. We did not detect any release of UA, with a sensitivity implying that photolyase is at least 2900 times less active toward UA‐DNA adducts than toward cis‐syn thyminethymine dimers. This indicates that any reversal of photoimmunosuppression by photoreactivation cannot significantly involve cleavage of UA‐DNA cyclobutane adducts.
Species-Specific Antibody Responses to the Recombinant 53-Kilodalton Excretory and Secretory Proteins in Mice Infected withTrichinellaspp
Authors: Nagano Isao , Wu Zhiliang , Takahashi Yuzo 
Published: January 2008

ABSTRACTThe 53-kDa proteins in larval excretory and secretory (E-S) products were expressed from fiveTrichinellaspecies (T. spiralis,T. britovi,T. nativa,T. pseudospiralis, andT. papuae), using theEscherichia coliexpression system, and the antibody responses to the 53-kDa recombinant proteins in mice infected withTrichinellaspp. were analyzed by Western blotting. The 53-kDa protein is conserved among the fiveTrichinellaspecies, with >60% similarity in amino acid sequences. The 53-kDa recombinant proteins ofT. spiralisandT. pseudospiralisreacted to sera from mice infected withT. spiralisandT. pseudospiralisat 8 days postinfection (p.i.), respectively. An antibody against the 53-kDa recombinant protein ofT. spiralisrecognized the 53-kDa protein in the crude extracts from adult worms and 30-day p.i. muscle larvae and E-S products from muscle larvae ofT. spiralisbut did not recognize any proteins fromT. pseudospiralis. The sera from the mice infected withT. spiralisstrongly reacted with the 53-kDa recombinant protein ofT. spiralisbut did not react with the 53-kDa recombinant proteins ofT. britovi,T. nativa,T. pseudospiralis, andT. papuae. Similarly, the sera from mice infected withT. britovi,T. nativa,T. pseudospiralis, orT. papuaestrongly reacted with the 53-kDa recombinant proteins ofT. britovi,T. nativa,T. pseudospiralis, orT. papuae, respectively. These results showed that the 53-kDa recombinant proteins provide early and species-specific antibody responses in mice infected withTrichinellaspp.
Detection of RNA of Mumps Virus during an Outbreak in a Population with a High Level of Measles, Mumps, and Rubella Vaccine Coverage
Authors: Bitsko Rebecca H. , Cortese Margaret M. , Dayan Gustavo H. , Rota Paul A. , Lowe Luis , Iversen Susan C. , Bellini William J. 
Published: January 2008

ABSTRACT
The duration of mumps virus RNA detection was studied during a mumps outbreak in a highly vaccinated university population. Seven of the eight reverse transcription-PCR-positive specimens were collected during the first 3 days of parotitis, suggesting that viral shedding is minimal after the first 3 days of symptoms.
Neutrophils Play an Essential Role in Cooperation with Antibody in both Protection against and Recovery from Pulmonary Infection with Influenza Virus in Mice
Authors: Fujisawa Haruo 
Published: January 2008

ABSTRACTThe role of polymorphonuclear leukocytes (PMN) in protection in the early phase and recovery in the late phase of influenza A virus infection was investigated by the depletion of PMN in, and passive transfer of anti-influenza virus antiserum to, mice with pulmonary infections. The depletion of PMN in normal mice by treatment with monoclonal antibody RB6-8C5 both increased the mortality rate and pulmonary virus titers from the early to the late phase after infection and delayed virus elimination in the late phase. The passive transfer of the antiserum to normal mice before or after infection abolished pulmonary virus propagation in the early phase, during 3 days, or rapidly decreased high virus titers in the plateau phase, on days 3 to 5, as well as accelerated virus elimination in the late phase, on day 7, after infection, respectively. The passive transfer of the antiserum to PMN-depleted mice could neither prevent the more rapid virus propagation in the early phase, diminish the higher virus titers in the plateau phase, nor accelerate the markedly delayed virus elimination in the late phase after infection in comparison to those for controls. The antibody responses to the virus began to increase on day 7 after infection in normal and PMN-depleted mice. The prevention of virus replication, cytotoxic activity in virus-infected cell cultures, and phagocytosis of the virus in vitro by PMN were all augmented in the presence of the antiserum. These results indicate that PMN play an essential role in virus elimination in both protection against and recovery from infection, in cooperation with the antibody response.
Lentiviral Vectors Encoding Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Receptor Genes Efficiently Convert Peripheral Blood CD8 T Lymphocytes into Cytotoxic T Lymphocytes with Potent In Vitro and In Vivo HIV-1-Specific Inhibitory Activity
Authors: Joseph Aviva , Zheng Jian Hua , Follenzi Antonia , DiLorenzo Teresa , Sango Kaori , Hyman Jaime , Chen Ken , Piechocka-Trocha Alicja , Brander Christian , Hooijberg Erik , Vignali Dario A. , Walker Bruce D. , Goldstein Harris 
Published: January 2008

ABSTRACTThe human immunodeficiency virus type 1 (HIV-1)-specific CD8 cytotoxic T-lymphocyte (CTL) response plays a critical role in controlling HIV-1 replication. Augmenting this response should enhance control of HIV-1 replication and stabilize or improve the clinical course of the disease. Although cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection in immunocompromised patients can be treated by adoptive transfer of ex vivo-expanded CMV- or EBV-specific CTLs, adoptive transfer of ex vivo-expanded, autologous HIV-1-specific CTLs had minimal effects on HIV-1 replication, likely a consequence of the inherently compromised qualitative function of HIV-1-specific CTLs derived from HIV-1-infected individuals. We hypothesized that this limitation could be circumvented by using as an alternative source of HIV-1-specific CTLs, autologous peripheral CD8+T lymphocytes whose antigen specificity is redirected by transduction with lentiviral vectors encoding HIV-1-specific T-cell receptor (TCR) α and β chains, an approach used successfully in cancer therapy. To efficiently convert peripheral CD8 lymphocytes into HIV-1-specific CTLs that potently suppress in vivo HIV-1 replication, we constructed lentiviral vectors encoding the HIV-1-specific TCR α and TCR β chains cloned from a CTL clone specific for an HIV Gag epitope, SL9, as a single transcript linked with a self-cleaving peptide. We demonstrated that transduction with this lentiviral vector efficiently converted primary human CD8 lymphocytes into HIV-1-specific CTLs with potent in vitro and in vivo HIV-1-specific activity. Using lentiviral vectors encoding an HIV-1-specific TCR to transform peripheral CD8 lymphocytes into HIV-1-specific CTLs with defined specificities represents a new immunotherapeutic approach to augment the HIV-1-specific immunity of infected patients.
Kaposi's Sarcoma-Associated Herpesvirus ORF57 Functions as a Viral Splicing Factor and Promotes Expression of Intron-Containing Viral Lytic Genes in Spliceosome-Mediated RNA Splicing
Authors: Majerciak Vladimir , Yamanegi Koji , Allemand Eric , Kruhlak Michael , Krainer Adrian R. , Zheng Zhi-Ming 
Published: January 2008

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 facilitates the expression of both intronless viral ORF59 genes and intron-containing viral K8 and K8.1 genes (V. Majerciak, N. Pripuzova, J. P. McCoy, S. J. Gao, and Z. M. Zheng, J. Virol. 81:1062-1071, 2007). In this study, we showed that disruption of ORF57 in a KSHV genome led to increased accumulation of ORF50 and K8 pre-mRNAs and reduced expression of ORF50 and K-bZIP proteins but had no effect on latency-associated nuclear antigen (LANA). Cotransfection of ORF57 and K8β cDNA, which retains a suboptimal intron of K8 pre-mRNA due to alternative splicing, promoted RNA splicing of K8β and production of K8α (K-bZIP). Although Epstein-Barr virus EB2, a closely related homolog of ORF57, had a similar activity in the cotransfection assays, herpes simplex virus type 1 ICP27 was inactive. This enhancement of RNA splicing by ORF57 correlates with the intact N-terminal nuclear localization signal motifs of ORF57 and takes place in the absence of other viral proteins. In activated KSHV-infected B cells, KSHV ORF57 partially colocalizes with splicing factors in nuclear speckles and assembles into spliceosomal complexes in association with low-abundance viral ORF50 and K8 pre-mRNAs and essential splicing components. The association of ORF57 with snRNAs occurs by ORF57-Sm protein interaction. We also found that ORF57 binds K8β pre-mRNAs in vitro in the presence of nuclear extracts. Collectively our data indicate that KSHV ORF57 functions as a novel splicing factor in the spliceosome-mediated splicing of viral RNA transcripts.
Cysteines Flanking the Internal Fusion Peptide Are Required for the Avian Sarcoma/Leukosis Virus Glycoprotein To Mediate the Lipid Mixing Stage of Fusion with High Efficiency
Authors: Delos Sue E. , Brecher Matthew B. , Chen Zaoying , Melder Deborah C. , Federspiel Mark J. , White Judith M. 
Published: January 2008

ABSTRACT
We previously showed that the cysteines flanking the internal fusion peptide of the avian sarcoma/leukosis virus subtype A (ASLV-A) Env (EnvA) are important for infectivity and cell-cell fusion. Here we define the stage of fusion at which the cysteines are required. The flanking cysteines are dispensable for receptor-triggered membrane association but are required for the lipid mixing step of fusion, which, interestingly, displays a high pH onset and a biphasic profile. Second-site mutations that partially restore infection partially restore lipid mixing. These findings indicate that the cysteines flanking the internal fusion peptide of EnvA (and perhaps by analogy Ebola virus glycoprotein) are important for the foldback stage of the conformational changes that lead to membrane merger.
Sialic Acid Is a Cellular Receptor for Coxsackievirus A24 Variant, an Emerging Virus with Pandemic Potential
Authors: Nilsson Emma C. , Jamshidi Fariba , Johansson Susanne M. C. , Oberste M. Steven , Arnberg Niklas 
Published: January 2008

ABSTRACTBinding to target cell receptors is a critical step in the virus life cycle. Coxsackievirus A24 variant (CVA24v) has pandemic potential and is a major cause of acute hemorrhagic conjunctivitis, but its cellular receptor has hitherto been unknown. Here we show that CVA24v fails to bind to and infect CHO cells defective in sialic acid expression. Binding of CVA24v to and infection of corneal epithelial cells are efficiently inhibited by treating cells with a sialic acid-cleaving enzyme or sialic acid-binding lectins and by treatment of the virus with soluble, multivalent sialic acid. Protease treatment of cells efficiently inhibited virus binding, suggesting that the receptor is a sialylated glycoprotein. Like enterovirus type 70 and influenza A virus, CVA24v can cause pandemics. Remarkably, all three viruses use the same receptor. Since several unrelated viruses with tropism for the eye use this receptor, sialic acid-based antiviral drugs that prevent virus entry may be useful for topical treatment of such infections.
The role of lactate in the exercise-induced human growth hormone response: evidence from McArdle disease
Authors: Godfrey R J , Whyte G P , Buckley J , Quinlivan R 
Published: January 2008

Purpose:Increased blood lactate concentration has been suggested as a primary stimulus for the exercise-induced growth hormone response (EIGR). Patients with McArdle disease are unable to produce lactate in response to exercise and thus offer a unique model to assess the role of lactate in the EIGR. Accordingly, McArdle’s patients were exercised to test the hypothesis that lactate is a major stimulus of the EIGR.Methods:11 patients with McArdle disease (3 male, 8 female; age: 35.5 (SD 13.9) years, height: 166 (8) cm, body mass: 75.2 (13.1) kg) were recruited for the study. The patients walked initially at 0.42 m/s, increasing by 0.14 m/s per 3 min stage. Exercise was terminated when participants completed 3 minutes at 1.80 m/s or when a Borg CR10 pain scale rating of “4” was reached. Stages were separated by 60 s for capillary blood sampling for analysis of hGH and blood lactate concentration.Results:McArdle’s patients’ blood lactate levels remained at resting levels (0.3–1.2 mmol/l) as exercise intensity increased. Nine out of 11 participants failed to demonstrate an EIGR obtaining hGH values below the clinical definition of a response (>3 μg/l).Conclusion:The absence of an EIGR in nine out of 11 participants suggests that lactate could play a major role in the EIGR in humans.
Antiangiogenic compounds interfere with chemotherapy of brain tumors due to vessel normalization
Authors: Claes An , Wesseling Pieter , Jeuken Judith , Maass Cathy , Heerschap Arend , Leenders William P.J. 
Published: January 2008

Abstract
Glioblastomas are highly aggressive primary brain tumors. Curative treatment by surgery and radiotherapy is generally impossible due to the presence of diffusely infiltrating tumor cells. Furthermore, the blood-brain barrier (BBB) in infiltrative tumor areas is largely intact, and this hampers chemotherapy as well. The occurrence of angiogenesis in these tumors makes these tumors attractive candidates for antiangiogenic therapies. Because antiangiogenic compounds have been shown to synergize with chemotherapeutic compounds in other tumor types, based on vessel normalization, there is a tendency toward such combination therapies for primary brain tumors also. However, vessel normalization in brain may result in restoration of the BBB with consequences for the efficacy of chemotherapeutic agents. In this study, we investigated this hypothesis. BALB/c nude mice with intracerebral xenografts of the human glioblastoma lines E98 or U87 were subjected to therapy with different dosages of vandetanib (an angiogenesis inhibitor), temozolomide (a DNA alkylating agent), or a combination (n &gt; 8 in each group). Vandetanib selectively inhibited angiogenic growth aspects of glioma and restored the BBB. It did not notably affect diffuse infiltrative growth and survival. Furthermore, vandetanib antagonized the effects of temozolomide presumably by restoration of the BBB and obstruction of chemodistribution to tumor cells. The tumor microenvironment is an extremely important determinant for the response to antiangiogenic therapy. Particularly in brain, antiangiogenic compounds may have adverse effects when combined with chemotherapy. Thus, use of such compounds in neuro-oncology should be reconsidered. [Mol Cancer Ther 2008;7(1):71–8]