bluuebunny/crossref_metadata_2025_split huggingface dataset:
Judges in Politics: USA
Authors: Vale Vivian 
Published: July 2007

‘HISTORIC’, ‘MOMENTOUS’ AND ‘REVOLUTIONARY’ ARE ONLY A FEW OF the epithets freely bestowed upon the case of Baker v. Carr. By that justly celebrated judgment of 26 March 1962 the US Supreme Court implied for the first time that the weight of an American's vote might no longer depend on whereabouts in the country he lived. It did so by ruling that a scheme of apportionment which permitted inequalities of population between electoral districts represented in a state's legislature could be challenged in federal (not merely state) courts, which had competence to protect the right in question. The tide of ensuing litigation attained a new level on I7 February 1964, when the Court in Wesberry v. Sanders held that a like symmetry must prevail among US Congressional districts also. High-water mark was reached on 15 June of that year with Reynolds v. Sims, where the constitution was held to requirethat the seats of both houses of a bicameral state legislature must be apportioned on a population basis. Simply stated, an individual's right to vote for state legislators is unconstitutionally impaired when its weight is in a substantial fashion diluted when compared with votes of citizens living in other parts of the State.
Involvement of Mitochondria–Caspase Pathway in Hemoporfin‐mediated Cell Death
Authors: Wei Yongqing , Kong Beihua , Song Kun , Qu Xun , Jin Qiong , Yang Qifeng 
Published: July 2007

AbstractHemoporfin is a novel second‐generation porphyrin‐related photosensitizer for ovarian cancer photodynamic treatment (PDT). The purpose of this study was to investigate the molecular mechanisms of Hemoporfin‐mediated photocytotoxicity. Human epithelial ovarian cancer cell line 3AO was incubated with different concentrations of Hemoporfin, and phototoxic effects of Hemoporfin on cells were determined using a Cell Viability Analyzer. Apoptosis or necrosis was determined by flow cytometry analysis using the Annexin V‐FITC apoptosis kit. Cellular caspase activation was determined using the fluorescent assay kit for caspase‐3 and caspase‐9. Rhodamine123 was used as a mitochondrial probe and Lucifer Yellow as a lysosomal probe to investigate the intracellular localization of Hemoporfin in 3AO cancer cells. We demonstrated that both high‐dose (30 μg mL−1) and low‐dose (3 μg mL−1) Hemoporfin significantly reduced the viability of ovarian cancer cell 3AO with light illumination, and the photocytotoxicity was dose‐dependent (P < 0.01). Using a mitochondrial fluorescence probe, we demonstrated a distinct mitochondrial aggregation in 3AO cells with a low concentration of Hemoporfin. Loss of mitochondrial membrane potential was detected as early as 1 h after Hemoporfin‐mediated PDT. PDT with low‐dose Hemoporfin predominantly induced apoptosis but not necrosis, and both caspase‐3 and caspase‐9 were activated. Based on our results, mitochondria play an important role in the Hemoporfin‐induced apoptosis, and mitochondria membrane potential loss initiated apoptosis via the activation of caspases. Understanding the mechanisms involved in PDT‐mediated apoptosis may improve its therapeutic efficacy and facilitate its transition into the clinic.
“Competitive Quenching”: A Mechanism by Which Perihydroxylated Perylenequinone Photosensitizers Can Prevent Adverse Phototoxic Damage Caused by Verteporfin During Photodynamic Therapy
Authors: Lavie Gad , Barliya Tilda , Mandel Mathilda , Blank Michael , Ron Yonina , Orenstein Arie , Livnat Tami , Friedman Noga , Weiner Lev , Sheves Mordechai , Weinberger Dov 
Published: July 2007

AbstractIncorporation of photodynamic therapy into clinical practice for induction of vascular photo‐occlusion highlights the need to prevent adverse phototoxicity to sensitive juxtaposed tissues, particularly in the retina. We developed a system termed “competitive quenching” to prevent adverse phototoxic damage. It involves differential compartmentalization of a photoactivator to the intravascular compartment for photoexcitation and delivery of phototoxicity to targeted vessels. A different photodynamic agent is partitioned to the extravascular retinal space to quench reactive oxygen species generated by photosensitization, thereby protecting the adjacent retinal tissues from adverse phototoxicity. The absorption spectra of quenchers must span wavelengths that are shorter and excluded from the spectral range of photoexcitation light to prevent photoactivation of the quencher. Perihydroxylated perylenequinones were found to be suitable to function as “competitive quenchers” with the prototype hypericin identified as a potent quencher. Here we examined the mechanisms operative in competitive quenching and suggest that hypericin forms a complex with verteporfin, thereby quenching singlet oxygen formation. Furthermore, we show that hypericin, with six phenolic hydroxyls, protects retinal and endothelial hybridoma cells from phototoxicity more effectively than the dimethyl tetrahydroxy helianthrone structural analog with only four such phenolic hydroxyls. The findings suggest that hydroxyl numbers contribute to the efficacy of competitive quenching.
Immunogenicity of Influenza Virus Vaccine Is Increased by Anti-Gal-Mediated Targeting to Antigen-Presenting Cells
Authors: Abdel-Motal Ussama M. , Guay Heath M. , Wigglesworth Kim , Welsh Raymond M. , Galili Uri 
Published: July 2007

ABSTRACTThis study describes a method for increasing the immunogenicity of influenza virus vaccines by exploiting the natural anti-Gal antibody to effectively target vaccines to antigen-presenting cells (APC). This method is based on enzymatic engineering of carbohydrate chains on virus envelope hemagglutinin to carry the α-Gal epitope (Galα1-3Galβ1-4GlcNAc-R). This epitope interacts with anti-Gal, the most abundant antibody in humans (1% of immunoglobulins). Influenza virus vaccine expressing α-Gal epitopes is opsonized in situ by anti-Gal immunoglobulin G. The Fc portion of opsonizing anti-Gal interacts with Fcγ receptors on APC and induces effective uptake of the vaccine virus by APC. APC internalizes the opsonized virus to transport it to draining lymph nodes for stimulation of influenza virus-specific T cells, thereby eliciting a protective immune response. The efficacy of such an influenza vaccine was demonstrated in α1,3galactosyltransferase (α1,3GT) knockout mice, which produce anti-Gal, using the influenza virus strain A/Puerto Rico/8/34-H1N1 (PR8). Synthesis of α-Gal epitopes on carbohydrate chains of PR8 virus (PR8αgal) was catalyzed by recombinant α1,3GT, the glycosylation enzyme that synthesizes α-Gal epitopes in cells of nonprimate mammals. Mice immunized with PR8αgaldisplayed much higher numbers of PR8-specific CD8+and CD4+T cells (determined by intracellular cytokine staining and enzyme-linked immunospot assay) and produced anti-PR8 antibodies with much higher titers than mice immunized with PR8 lacking α-Gal epitopes. Mice immunized with PR8αgalalso displayed a much higher level of protection than PR8 immunized mice after being challenged with lethal doses of live PR8 virus. We suggest that a similar method for increasing immunogenicity may be applicable to avian influenza vaccines.
Bile Acids Promote the Expression of Hepatitis C Virus in Replicon-Harboring Cells
Authors: Chang Kyeong-Ok , George David W. 
Published: July 2007

ABSTRACT

Hepatitis C virus (HCV) is a cause of chronic liver disease, with more than 170 million persistently infected individuals worldwide. Although the combination therapy of alpha interferon (IFN-α) and ribavirin is effective for chronic HCV infection, around half of all patients infected with HCV genotype 1 fail to show sustained virologic responses and remain chronically infected. Previously, we demonstrated that bile acids were essential for growth of porcine enteric calicivirus in cell culture in association with down-regulation of IFN responses. Because hepatocytes are exposed to high concentrations of bile acids in the liver, we hypothesized that bile acids have similar effects on HCV replication. We incubated HCV replicon-harboring cells (genotype 1b, Con1) in the presence of various bile acids and monitored the expression of HCV RNA and protein (NS5B). The addition of an individual bile acid (deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, or glycochenodeoxycholic acid) in the medium increased the levels of HCV RNA and proteins up to fivefold at 48 h of incubation. An antagonist of bile acid receptor farnesoid X receptor (FXR),
Z
-guggulsterone, reduced the bile acid-mediated increase of HCV RNA. When IFN (α or γ) and each bile acid were incubated together, we observed that bile acid significantly reduced the anti-HCV effect of IFN. These results indicated that bile acids are factors in the failure of IFN treatment for certain patients infected with HCV genotype 1. Our finding may also contribute to the establishment of better regimens for treatment of chronic HCV infections by including agents altering the bile acid-mediated FXR pathway.
The effect of protective headgear on head injuries and concussions in adolescent football (soccer) players
Authors: Delaney J S , Al-Kashmiri A , Drummond R , Correa J A 
Published: July 2007

Objective:To examine the effects of protective headgear in adolescent football (soccer) players.Design:Cross-sectional study.Setting:Oakville Soccer Club, Oakville, Canada.Participants:Football players aged 12–17 years.Intervention:A questionnaire examining the 2006 football season using self-reported symptoms.Main outcome measures:The number of concussions experienced during the current football season, the duration of symptoms, injuries to the head and face and any associated risk factors for these injuries.Results:In the population studied, 47.8% had experienced symptoms of a concussion during the current football year. 26.9% of athletes who wore headgear (HG) and 52.8% of those who did not wear headgear (No-HG) had concussions. Approximately 4 out of 5 athletes in each group did not realize they had suffered a concussion. More than one concussion was experienced by 50.0% of the concussed HG athletes and 69.3% of the concussed No-HG group. 23.9% of all concussed players experienced symptoms for at least 1 day or longer. Variables that increased the risk of suffering a concussion during the 2006 football year included being female and not wearing headgear. Being female and not wearing football headgear increased the risk of suffering an abrasion, laceration or contusion on areas of the head covered by football headgear.Conclusion:Adolescent football players experience a significant number of concussions. Being female may increase the risk of suffering a concussion and injuries on the head and face, while the use of football headgear may decrease the risk of sustaining these injuries.
Endothelin-1 blockade prevents COX2induction and TXA2production in the fructose hypertensive ratThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Jiang Jihong , Tran Linda , Vasudevan Harish , Xia Zhengyuan , Yuen Violet G. , McNeill John H. 
Published: July 2007

Feeding rats with a high fructose diet results in insulin resistance and hypertension. Fructose-hypertensive rats (FHR) have increased vascular levels of endothelin-1 (ET-1) and thromboxane (TXA2). We have previously shown that chronic treatment with either the dual endothelin receptor blocker, bosentan, or the thromboxane synthase inhibitor, dazmegrel, prevented fructose-induced increases in blood pressure, suggesting that both ET-1 and TXA2play important roles in the development of hyperinsulinemia/insulin resistance-associated hypertension. In this study, we investigated the potential interrelationship between ET-1 and TXA2in the development of fructose-induced hypertension in vivo. Male Wistar rats were fed on a high fructose diet for 9 weeks. Either bosentan or dazmegrel treatment (daily by oral gavage) was initiated 3 weeks after the start of fructose feeding for a total duration of 6 weeks. At the end of drug treatment, blood and aorta were collected from each animal. Plasma thromboxane B2(TXB2), a stable TXA2metabolite, increased significantly in FHR and was reduced to control level by both chronic bosentan and dazmegrel treatment. Protein expression of cyclooxygenase 2 (COX2) was elevated significantly in FHR aortas and treatment with bosentan and dazmegrel corrected these changes. These results indicate that the actions of ET-1 in the aorta of FHR may be mediated through COX2-derived TXA2. Bosentan may prevent the development of hypertension in fructose-fed rats through inhibition of COX2induction and subsequently the reduction in plasma TXA2.
O-Glycosylation Regulates LNCaP Prostate Cancer Cell Susceptibility to Apoptosis Induced by Galectin-1
Authors: Valenzuela Hector F. , Pace Karen E. , Cabrera Paula V. , White Rachel , Porvari Katja , Kaija Helena , Vihko Pirkko , Baum Linda G. 
Published: July 2007

AbstractResistance to apoptosis is a critical feature of neoplastic cells. Galectin-1 is an endogenous carbohydrate-binding protein that induces death of leukemia and lymphoma cells, breast cancer cells, and the LNCaP prostate cancer cell line, but not other prostate cancer cell lines. To understand the mechanism of galectin-1 sensitivity of LNCaP cells compared with other prostate cancer cells, we characterized glycan ligands that are important for conferring galectin-1 sensitivity in these cells, and analyzed expression of glycosyltransferase genes in galectin-1–sensitive, prostate-specific antigen–positive (PSA+) LNCaP cells compared with a galectin-1–resistant PSA− LNCaP subclone. We identified one glycosyltransferase, core 2 N-acetylglucosaminyltransferase, which is down-regulated in galectin-1–resistant PSA− LNCaP cells compared with galectin-1–sensitive PSA+ LNCaP cells. Intriguingly, this is the same glycosyltransferase required for galectin-1 susceptibility of T lymphoma cells, indicating that similar O-glycan ligands on different polypeptide backbones may be common death trigger receptors recognized by galectin-1 on different types of cancer cells. Blocking O-glycan elongation by expressing α2,3-sialyltransferase 1 rendered LNCaP cells resistant to galectin-1, showing that specific O-glycans are critical for galectin-1 susceptibility. Loss of galectin-1 susceptibility and synthesis of endogenous galectin-1 has been proposed to promote tumor evasion of immune attack; we found that galectin-1–expressing prostate cancer cells killed bound T cells, whereas LNCaP cells that do not express galectin-1 did not kill T cells. Resistance to galectin-1–induced apoptosis may directly contribute to the survival of prostate cancer cells as well as promote immune evasion by the tumor. [Cancer Res 2007;67(13):6155–62]
BRCA1 Activates a G2-M Cell Cycle Checkpoint following 6-Thioguanine–Induced DNA Mismatch Damage
Authors: Yamane Kazuhiko , Schupp Jane E. , Kinsella Timothy J. 
Published: July 2007

Abstract
Human DNA mismatch repair (MMR) is involved in the response to certain chemotherapy drugs, including 6-thioguanine (6-TG). Consistently, MMR-deficient human tumor cells show resistance to 6-TG damage as manifested by a reduced G2-M arrest and decreased apoptosis. In this study, we investigate the role of the BRCA1 protein in modulating a 6-TG–induced MMR damage response, using an isogenic human breast cancer cell line model, including a BRCA1 mutated cell line (HCC1937) and its transfectant with a wild-type BRCA1 cDNA. The MMR proteins MSH2, MSH6, MLH1, and PMS2 are similarly detected in both cell lines. BRCA1-mutant cells are more resistant to 6-TG than BRCA1-positive cells in a clonogenic survival assay and show reduced apoptosis. Additionally, the mutated BRCA1 results in an almost complete loss of a G2-M cell cycle checkpoint response induced by 6-TG. Transfection of single specific small interfering RNAs (siRNA) against MSH2, MLH1, ATR, and Chk1 in BRCA1-positive cells markedly reduces the BRCA1-dependent G2-M checkpoint response. Interestingly, ATR and Chk1 siRNA transfection in BRCA1-positive cells shows similar levels of 6-TG cytotoxicity as the control transfectant, whereas MSH2 and MLH1 siRNA transfectants show 6-TG resistance as expected. DNA MMR processing, as measured by the number of 6-TG–induced DNA strand breaks using an alkaline comet assay (±z-VAD-fmk cotreatment) and by levels of iododeoxyuridine-DNA incorporation, is independent of BRCA1, suggesting the involvement of BRCA1 in the G2-M checkpoint response to 6-TG but not in the subsequent excision processing of 6-TG mispairs by MMR. [Cancer Res 2007;67(13):6286–92]
Amphipathic Peptide-Based Fusion Peptides and Immunoconjugates for the Targeted Ablation of Prostate Cancer Cells
Authors: Rege Kaushal , Patel Suraj J. , Megeed Zaki , Yarmush Martin L. 
Published: July 2007

Abstract
We describe the design, generation, and in vitro evaluation of targeted amphipathic fusion peptides and immunoconjugates for the ablation of prostate cancer cells. The overexpression of the prostate-specific membrane antigen (PSMA) was exploited as means to specifically deliver cytotoxic peptides to prostate cancer cells. Cationic amphipathic lytic peptides were chosen as cytotoxic agents due to their ability to depolarize mitochondrial membranes and induce apoptosis. Specific delivery of the lytic peptide was facilitated by PSMA-targeting peptides and antibodies. Our results indicate that although the use of PSMA-targeted peptides only modestly enhanced the cytotoxic activity of the lytic peptide, peptide-antibody conjugates were two orders of magnitude more potent than untargeted peptide. In addition to quantifying the cytotoxic activities of the individual constructs, we also investigated the mechanisms of cell death induced by the fusion peptides and immunoconjugates. Although fusion peptides induced oncotic/necrotic death in cells, treatment with immunoconjugates resulted in apoptotic death. In summary, immunoconjugates based on lytic peptides are a promising class of therapeutics for prostate cancer therapy and warrant further investigation. [Cancer Res 2007;67(13):6368–75]
EGFR Activation Results in Enhanced Cyclooxygenase-2 Expression through p38 Mitogen-Activated Protein Kinase–Dependent Activation of the Sp1/Sp3 Transcription Factors in Human Gliomas
Authors: Xu Kaiming , Shu Hui-Kuo G. 
Published: July 2007

Abstract
Expression of cyclooxygenase-2 (COX-2) has been linked to many cancers and may contribute to malignant phenotypes, including enhanced proliferation, angiogenesis, and resistance to cytotoxic therapies. Malignant gliomas are highly aggressive brain tumors that display many of these characteristics. One prominent molecular abnormality discovered in these astrocytic brain tumors is alteration of epidermal growth factor (EGF) receptor (EGFR) through gene amplification and/or mutation resulting in excessive signaling from this receptor. We found that EGF-mediated stimulation of EGFR tyrosine kinase in human glioma cell lines induces expression of both COX-2 mRNA and protein. The p38 mitogen-activated protein kinase (p38-MAPK) pathway was a strong downstream factor in this activation with inhibition of this pathway leading to strong suppression of COX-2 induction. The p38-MAPK pathway can activate the Sp1/Sp3 transcription factors and this seems necessary for EGFR-dependent transactivation of the COX-2 promoter. Analysis of COX-2 promoter/luciferase constructs revealed that transcriptional activation of the COX-2 promoter by EGFR requires the Sp1 binding site located at −245/−240. Furthermore, Sp1/Sp3 binding to this site in the promoter is enhanced by EGFR activation both in vitro and in vivo. Enhanced DNA binding by Sp1/Sp3 requires p38-MAPK activity and correlates with increased phosphorylation of the Sp1 transcription factor. Thus, EGFR activation in malignant gliomas can transcriptionally activate COX-2 expression in a process that requires p38-MAPK and Sp1/Sp3. Finally, treatment of glioma cell lines with prostaglandin E2, the predominant product of COX-2 activity, results in increased vascular endothelial growth factor expression, thus potentially linking elevations in COX-2 expression with tumor angiogenesis in malignant gliomas. [Cancer Res 2007;67(13):6121–9]
Are Peroxisome Proliferator-Activated Receptors Involved in Skeletal Muscle Wasting during Experimental Cancer Cachexia? Role of β2-Adrenergic Agonists
Authors: Fuster Gemma , Busquets Sílvia , Ametller Elisabet , Olivan Mireia , Almendro Vanessa , Fontes de Oliveira Cibely Cristine , Figueras Maite , López-Soriano Francisco J. , Argilés Josep M. 
Published: July 2007

Abstract
Implantation of the Yoshida AH-130 ascites hepatoma to rats resulted in a decrease in muscle weight 7 days after the inoculation of the tumor. These changes were associated with increases in the mRNA content for both peroxisome proliferator-activated receptor (PPAR) γ and PPARδ in skeletal muscle. The increase in gene expression for these transcription factors was related to increases in the expression of several genes involved in fatty acid transport, activation, and oxidation. Tumor burden also resulted in increases in PPARγ coactivator-1α gene expression and pyruvate dehydrogenase kinase 4. All these changes in lipid metabolism genes suggest that a metabolic shift occurs in skeletal muscle of tumor-bearing rats toward a more oxidative phenotype. Formoterol treatment to tumor-bearing rats resulted in an amelioration of all the changes observed as a result of tumor burden. Administration of this β2-adrenergic agonist also resulted in a decrease in mRNA content of muscle PPARα, PPARδ, and PPARγ, as well as in mRNA levels of many of the genes involved in both lipid and mitochondrial metabolism. All these results suggest an involvement of the different PPARs as transcription factors related with muscle wasting and also indicate that a possible mode of action of the anticachectic compound formoterol may involve a normalization of the levels of these transcription factors. [Cancer Res 2007;67(13):6512–9]
Quantitative Assessment of the p53-Mdm2 Feedback Loop Using Protein Lysate Microarrays
Authors: Ramalingam Sundhar , Honkanen Peter , Young Lynn , Shimura Tsutomu , Austin John , Steeg Patricia S. , Nishizuka Satoshi 
Published: July 2007

Abstract
Mathematical simulations of the p53-Mdm2 feedback loop suggest that both proteins will exhibit impulsive expression characteristics in response to high cellular stress levels. However, little quantitative experimental evaluation has been done, particularly of the phosphorylated forms. To evaluate the mathematical models experimentally, we used lysate microarrays from an isogenic pair of γ-ray–irradiated cell lysates from HCT116 (p53+/+ and p53−/−). Both p53 and Mdm2 proteins showed expected pulses in the wild type, whereas no pulses were seen in the knockout. Based on experimental observations, we determined model parameters and generated an in silico “knockout,” reflecting the experimental data, including phosphorylated proteins. [Cancer Res 2007;67(13):6247–52]