bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclooxygenase-2 Inhibitor NS-398 Protects Neuronal Cultures From Lipopolysaccharide-Induced Neurotoxicity
Authors: Araki Eiichi , Forster Colleen , Dubinsky Janet M. , Ross M. Elizabeth , Iadecola Costantino 
Published: October 2007

Background and Purpose—The prostanoid-synthesizing enzyme cyclooxygenase (COX)-2 is markedly upregulated after cerebral ischemia and may participate in the mechanisms by which postischemic inflammation contributes to the late stages of ischemic brain injury. In the present study, we sought to provide additional evidence for a role of COX-2 in the mechanisms of neurotoxicity associated with inflammation.Methods—Nine-day-old neuronal-glial cultures, prepared from the cerebral cortex of newborn C57BL/6J mice, were exposed to lipopolysaccharide (LPS), a potent proinflammatory agent. The contribution of COX-2 was investigated by using the COX-2 inhibitor NS-398.Results—LPS produced a dose-dependent (0.001 to 10 μg/mL) and selective neuronal death that was well developed 72 hours after treatment. The effect was associated with a marked increase in the concentration of the COX reaction product prostaglandin E2(PGE2) and of the cytokine tumor necrosis factor-α (TNF-α). NS-398 (10 μmol/L) blocked the PGE2increase, attenuated the TNF-α increase, and prevented the neuronal death produced by LPS. TNF-α-blocking antibodies attenuated LPS-induced neuronal death, but the protection was less pronounced than that afforded by NS-398. LPS failed to elevate PGE2or to produce cell death in neuron-enriched cultures, suggesting that glial cells are required for these effects.Conclusions—COX-2, in part through TNF-α-related mechanisms, contributes to LPS-induced neuronal death. The data support the hypothesis that COX-2, in addition to its role in glutamate excitotoxicity, participates in the cytotoxicity associated with inflammation.
Redo Carotid Endarterectomy Versus Primary Carotid Endarterectomy
Authors: AbuRahma Ali F. , Jennings Tucker G. , Wulu John T. , Tarakji Lisa , Robinson Patrick A. 
Published: October 2007

Background and Purpose—Several authorities have recently advocated carotid stenting for recurrent carotid stenosis because of the perception that redo surgery has a higher complication rate than primary carotid endarterectomy (CEA). This study compares the early and late results of reoperations versus primary CEA.Methods—All reoperations for recurrent carotid stenosis performed during a recent 7-year period by a single vascular surgeon were compared with primary CEA. Because all redo CEAs were done with polytetrafluoroethylene (PTFE) or vein patch closure, we only analyzed those primary CEAs that used the same patch closures. A Kaplan-Meier life-table analysis was used to estimate stroke-free survival rates and freedom from ≥50% recurrent stenosis.Results—Of 547 primary CEAs, 265 had PTFE or saphenous vein patch closure, and 124 reoperations had PTFE or vein patch closure during the same period. Both groups had similar demographic characteristics. The indications for reoperation and primary CEA were symptomatic stenosis in 78% and 58% of cases and asymptomatic ≥80% stenosis in 22% and 42% of cases, respectively (P<0.001). The 30-day perioperative stroke and transient ischemic attack rates for reoperation and primary CEA were 4.8% versus 0.8% (P=0.015) and 4% versus 1.1%, respectively, with no perioperative deaths in either group. Cranial nerve injury was noted in 17% of reoperation patients versus 5.3% of primary CEA patients; however, most of these injuries were transient (P<0.001). Mean hospital stay was 1.8 days for reoperation versus 1.6 days for primary CEA. Cumulative rates of stroke-free survival and freedom from ≥50% recurrent stenosis for reoperation and primary CEA at 1, 3, and 5 years were 96%, 91%, and 82% and 98%, 96%, and 95% versus 94%, 92%, and 91% and 98%, 96%, and 96%, respectively (no significant differences).Conclusions—Reoperation carries higher perioperative stroke and cranial nerve injury rates than primary CEA. However, reoperations are durable and have stroke-free survival rates that are similar to primary CEA. These considerations should be kept in mind when carotid stenting is recommended instead of reoperation.
New insight into the role of the β3 subunit of the GABAA-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout
Authors: Ferguson Carolyn , Hardy Steven L , Werner David F , Hileman Stanley M , DeLorey Timothy M , Homanics Gregg E 
Published: October 2007

AbstractBackgroundThe β3 subunit of the γ-aminobutyric acid type A receptor (GABAA-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.ResultsGene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.ConclusionConditional inactivation of the β3 gene revealed novel insight into the function of this GABAA-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.
Rapid diagnosis of experimental meningitis by bacterial heat production in cerebrospinal fluid
Authors: Trampuz Andrej , Steinhuber Andrea , Wittwer Matthias , Leib Stephen L 
Published: October 2007

Abstract

Background
Calorimetry is a nonspecific technique which allows direct measurement of heat generated by biological processes in the living cell. We evaluated the potential of calorimetry for rapid detection of bacterial growth in cerebrospinal fluid (CSF) in a rat model of bacterial meningitis.

Methods
Infant rats were infected on postnatal day 11 by direct intracisternal injection with either Streptococcus pneumoniae, Neisseria meningitidis or Listeria monocytogenes. Control animals were injected with sterile saline or heat-inactivated S. pneumoniae. CSF was obtained at 18 hours after infection for quantitative cultures and heat flow measurement. For calorimetry, 10 μl and 1 μl CSF were inoculated in calorimetry ampoules containing 3 ml trypticase soy broth (TSB).

Results
The mean bacterial titer (± SD) in CSF was 1.5 ± 0.6 × 108 for S. pneumoniae, 1.3 ± 0.3 × 106 for N. meningitidis and 3.5 ± 2.2 × 104 for L. monocytogenes. Calorimetric detection time was defined as the time until heat flow signal exceeded 10 μW. Heat signal was detected in 10-μl CSF samples from all infected animals with a mean (± SD) detection time of 1.5 ± 0.2 hours for S. pneumoniae, 3.9 ± 0.7 hours for N. meningitidis and 9.1 ± 0.5 hours for L. monocytogenes. CSF samples from non-infected animals generated no increasing heat flow (<10 μW). The total heat was the highest in S. pneumoniae ranging from 6.7 to 7.5 Joules, followed by L. monocytogenes (5.6 to 6.1 Joules) and N. meningitidis (3.5 to 4.4 Joules). The lowest detectable bacterial titer by calorimetry was 2 cfu for S. pneumoniae, 4 cfu for N. meningitidis and 7 cfu for L. monocytogenes.

Conclusion
By means of calorimetry, detection times of <4 hours for S. pneumoniae and N. meningitidis and <10 hours for Listeria monocytogenes using as little as 10 μl CSF were achieved. Calorimetry is a new diagnostic method allowing rapid and accurate diagnosis of bacterial meningitis from a small volume of CSF.
Is the tobacco control movement misrepresenting the acute cardiovascular health effects of secondhand smoke exposure? An analysis of the scientific evidence and commentary on the implications for tobacco control and public health practice
Authors: Siegel Michael 
Published: October 2007

AbstractWhile chronic exposure to secondhand smoke has been well recognized as a cause of heart disease in nonsmokers, there has been recent speculation about the potential acute cardiovascular effects of transient exposure to secondhand smoke among nonsmokers; in particular, the possibility that such exposure could increase the risk of acute myocardial infarction even in an otherwise healthy nonsmoker. This paper reviews the claims being made by a number of anti-smoking and public health groups regarding the acute cardiovascular effects of secondhand smoke exposure among otherwise healthy adults, analyzes the validity of these claims based on a review of the scientific evidence, and discusses the implications of the findings for tobacco control and public health practice. Based on the analysis, it appears that a large number of anti-smoking organizations are making inaccurate claims that a single, acute, transient exposure to secondhand smoke can cause severe and even fatal cardiovascular events in healthy nonsmokers. The dissemination of inaccurate information by anti-smoking groups to the public in support of smoking bans is unfortunate because it may harm the tobacco control movement by undermining its credibility, reputation, and effectiveness. Disseminating inaccurate information also represents a violation of basic ethical principles that are a core value of public health practice that cannot and should not be sacrificed, even for a noble end such as protecting nonsmokers from secondhand smoke exposure. How the tobacco control movement responds to this crisis of credibility will go a long way towards determining the future effectiveness of the movement and its ability to continue to save lives and protect the public's health.
Electrospun nitrocellulose and nylon: Design and fabrication of novel high performance platforms for protein blotting applications
Authors: Manis Ashley E , Bowman James R , Bowlin Gary L , Simpson David G 
Published: October 2007

Abstract

Background
Electrospinning is a non-mechanical processing strategy that can be used to process a variety of native and synthetic polymers into highly porous materials composed of nano-scale to micron-scale diameter fibers. By nature, electrospun materials exhibit an extensive surface area and highly interconnected pore spaces. In this study we adopted a biological engineering approach to ask how the specific unique advantages of the electrospinning process might be exploited to produce a new class of research/diagnostic tools.

Methods
The electrospinning properties of nitrocellulose, charged nylon and blends of these materials are characterized.

Results
Nitrocellulose electrospun from a starting concentration of < 110 mg/ml acetone deposited as 4–8 μm diameter beads; at 110 mg/ml-to-140 mg/ml starting concentrations, this polymer deposited as 100–4000 nm diameter fibers. Nylon formed fibers when electrospun from 60–140 mg/ml HFIP, fibers ranged from 120 nm-6000 nm in diameter. Electrospun nitrocellulose exhibited superior protein retention and increased sensitivity in slot blot experiments with respect to the parent nitrocellulose material. Western immunoblot experiments using fibronectin as a model protein demonstrated that electrospun nylon exhibits increased protein binding and increased dynamic range in the chemiluminescence detection of antigens than sheets of the parent starting material. Composites of electrospun nitrocellulose and electrospun nylon exhibit high protein binding activity and provide increased sensitivity for the immuno-detection of antigens.

Conclusion
The flexibility afforded by electrospinning process makes it possible to tailor blotting membranes to specific applications. Electrospinning has a variety of potential applications in the clinical diagnostic field of use.
Development of a Cryptosporidium oocyst assay using an automated fiber optic-based biosensor
Authors: Kramer Marianne F , Vesey Graham , Look Natasha L , Herbert Ben R , Simpson-Stroot Joyce M , Lim Daniel V 
Published: October 2007

Abstract
An intestinal protozoan parasite, Cryptosporidium parvum, is a major cause of waterborne gastrointestinal disease worldwide. Detection of Cryptosporidium oocysts in potable water is a high priority for the water treatment industry to reduce potential outbreaks among the consumer populace. Anti-Cryptosporidium oocyst polyclonal and monoclonal antibodies were tested as capture and detection reagents for use in a fiber optic biosensor assay for the detection of Cryptosporidium oocysts. Antibodies were validated using enzyme-linked immunosorbent assays, flow cytometry, Western blotting and fluorescent microscopy. Oocysts could be detected at a concentration of 105 oocysts/ml when the polyclonal antibodies were used as the capture and detection reagents. When oocysts were boiled prior to detection, a ten-fold increase in sensitivity was achieved using the polyclonal antibody. Western blotting and immunofluorescence revealed that both the monoclonal and polyclonal antibodies recognize a large (>300 kDa) molecular weight mucin-like antigen present on the surface of the oocyst wall. The polyclonal antibody also reacted with a small (105 kDa) molecular weight antigen that was present in boiled samples of oocysts. Preliminary steps to design an in-line biosensor assay system have shown that oocysts would have to be concentrated from water samples and heat treated to allow detection by a biosensor assay.
The ribosomal protein genes and Minute loci of Drosophila melanogaster
Authors: Marygold Steven J , Roote John , Reuter Gunter , Lambertsson Andrew , Ashburner Michael , Millburn Gillian H , Harrison Paul M , Yu Zhan , Kenmochi Naoya , Kaufman Thomas C , Leevers Sally J , Cook Kevin R 
Published: October 2007

Abstract
Background
Mutations in genes encoding ribosomal proteins (RPs) have been shown to cause an array of cellular and developmental defects in a variety of organisms. In Drosophila melanogaster, disruption of RP genes can result in the 'Minute' syndrome of dominant, haploinsufficient phenotypes, which include prolonged development, short and thin bristles, and poor fertility and viability. While more than 50 Minute loci have been defined genetically, only 15 have so far been characterized molecularly and shown to correspond to RP genes.

Results
We combined bioinformatic and genetic approaches to conduct a systematic analysis of the relationship between RP genes and Minute loci. First, we identified 88 genes encoding 79 different cytoplasmic RPs (CRPs) and 75 genes encoding distinct mitochondrial RPs (MRPs). Interestingly, nine CRP genes are present as duplicates and, while all appear to be functional, one member of each gene pair has relatively limited expression. Next, we defined 65 discrete Minute loci by genetic criteria. Of these, 64 correspond to, or very likely correspond to, CRP genes; the single non-CRP-encoding Minute gene encodes a translation initiation factor subunit. Significantly, MRP genes and more than 20 CRP genes do not correspond to Minute loci.

Conclusion
This work answers a longstanding question about the molecular nature of Minute loci and suggests that Minute phenotypes arise from suboptimal protein synthesis resulting from reduced levels of cytoribosomes. Furthermore, by identifying the majority of haplolethal and haplosterile loci at the molecular level, our data will directly benefit efforts to attain complete deletion coverage of the D. melanogaster genome.
Prospective Determination of Prevalence of Lynch Syndrome in Young Women With Endometrial Cancer
Authors: Lu Karen H. , Schorge John O. , Rodabaugh Kerry J. , Daniels Molly S. , Sun Charlotte C. , Soliman Pamela T. , White Kristin G. , Luthra Rajyalakshmi , Gershenson David M. , Broaddus Russell R. 
Published: October 2007

Purpose Age younger than 50 years at the time of colon cancer diagnosis is often used as a screening criterion for Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). The purpose of this study was to determine the prevalence of MLH1, MSH2, and MSH6 mutations in an unselected cohort of women diagnosed with endometrial cancer at age younger than 50 years. Methods A prospective, multicenter study was performed at three institutions. After written consent was obtained, germline mutation testing by full sequencing and large deletion analysis of the MLH1, MSH2, and MSH6 genes was performed. Tumor studies included immunohistochemistry of MLH1, MSH2, and MSH6; microsatellite instability analysis; and hypermethylation of the MLH1 promoter. Results Of the 100 women, nine (9%; 95% CI, 4.2 to 16.4) carried a deleterious germline mutation: seven women with mutations in MSH2, one woman with a mutation in MLH1, and one woman with a mutation in MSH6. Two additional women had molecular studies consistent with the diagnosis of Lynch syndrome. The mean body mass index (BMI) for the entire cohort was 34.4, which is significantly higher than 29.2, the mean BMI for the mutation carriers. Predictors of finding a germline mutation included having a first-degree relative with a Lynch syndrome–associated cancer, endometrial tumor with loss of MSH2 expression, tumors with high microsatellite instability, and lower BMI. Conclusion In this prospective study of endometrial cancer patients younger than age 50 years, 9% were found to carry germline Lynch syndrome–associated mutations. In addition to young age of onset, family history, BMI, and molecular tumor studies can improve the likelihood of identifying a Lynch syndrome–associated germline mutation in MLH1, MSH2, and MSH6.
American Society of Clinical Oncology Endorsement of the Cancer Care Ontario Practice Guideline on Nonhormonal Therapy for Men With Metastatic Hormone-Refractory (castration-resistant) Prostate Cancer
Authors: Basch Ethan M. , Somerfield Mark R. , Beer Tomasz M. , Carducci Michael A. , Higano Celestia S. , Hussain Maha H.A. , Scher Howard I. 
Published: October 2007

Purpose In 2006, the American Society of Clinical Oncology (ASCO) Board of Directors (BOD) approved a policy and a set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. Methods The Cancer Care Ontario (CCO) Guideline on Non-Hormonal Therapy for Men With Metastatic Hormone-Refractory Prostate Cancer (HRPC) was reviewed for developmental rigor by methodologists. An ad hoc prostate cancer guideline review panel consisting of prostate cancer experts reviewed the content. Results The ASCO ad hoc prostate cancer guideline review panel concurred that the recommendations are clear, thorough, based on the most relevant scientific evidence in this content area, and present options that will be acceptable to patients. The CCO guideline was subsequently endorsed by the ASCO BOD. The guideline recommends the use of docetaxel, prednisone/hydrocortisone, and/or mitoxantrone in specific settings. Docetaxel-based chemotherapy is the only treatment that has demonstrated an overall survival benefit in men with HRPC. The use of estramustine in combination with other cytotoxic agents is not recommended. Continued gonadal androgen suppression and discontinuance of antiandrogens is recommended for men receiving chemotherapy. Conclusion The review panel agreed with the recommendations as stated in the CCO guideline, with the following qualifications: two of the ASCO content reviewers noted the importance of considering other, nonhormonal therapies in this context that are beyond the scope of this guideline. The review panel notes that CCO has published separate guidelines on radiopharmaceuticals and bisphosphonates in men with castration-resistant (ie, hormone-refractory) metastatic prostate cancer.
Methylprednisolone, cortisol and the cell-mediated immune response in children after ventricular septal defect repair
Authors: Grosek Stefan , Ihan Alojz , Wraber Branka , Gabrijelcic Tone , Kosin Miro , Osredkar Josko , Gmeiner Günter , Grabnar Iztok , Primozic Janez 
Published: October 2007

AbstractClin Chem Lab Med 2007;45:1366–72.
Cytokines and growth factors in mostly atherosclerotic patients on hemodialysis determined by biochip array technology
Authors: Sertic Jadranka , Slavicek Jasna , Bozina Nada , Malenica Branko , Kes Petar , Reiner Zeljko 
Published: October 2007

AbstractClin Chem Lab Med 2007;45:1347–52.
Biochemical properties of endogenous presenilin 1 and presenilin 2 in cultured human B-lymphocytes
Authors: Bojarski Lukasz , Lewandowicz Andrzej , Blazejczyk Magdalena , Sobczak Adam , Kuznicki Jacek , Wojda Urszula 
Published: October 2007

AbstractClin Chem Lab Med 2007;45:1273–6.
Genetic Susceptibility to Cancer
Authors: Spain Sarah , Tomlinson Ian P. M. 
Published: October 2007

AbstractMany cancers and benign tumours probably result, at least in part, from inherited factors. In addition, the presenting features of cancers, response to treatment, and outcome may depend on genetic influences. For most patients, these genetic factors are likely to take the form of alleles with small effects on risk or tumour behaviour, and most of the genes involved have not yet been characterized. The Mendelian (single gene) predisposition disorders that are associated with a high lifetime risk of cancer and/or benign tumours have been better characterized. Although there is considerable heterogeneity in these conditions in terms of the genes involved, tumour site, multiplicity of tumours, molecular pathways involved, and underlying mechanisms of tumourigenesis, most Mendelian tumour susceptibility genes are dominantly inherited tumour suppressors that normally restrain cell proliferation in some way, or recessively inherited alleles involved in DNA repair or the maintenance of genome integrity. Many of the genes involved in the Mendelian syndromes are mutated or otherwise altered somatically in sporadic cancers. Genetic testing for the Mendelian conditions is now largely routine, but should large numbers of low‐risk alleles be identified, the potential financial burden of population‐level genetic testing will be great. It will, therefore, be important to make sure that this testing is used selectively for cancers for which prevention is possible and is most effectively targeted at those with increased genetic risk.
HumanDNATumour Viruses
Authors: Talukdar Sabrina , Herrington C. Simon 
Published: October 2007

AbstractThe four human deoxyribonucleic acid (DNA) tumour viruses recognised by the World Health Organisation to be carcinogenic cause tumours by virtue of their reliance on host cell machinery for replication. The viruses modify host cells in such a way that they are susceptible to the synergistic effects of other carcinogens, resulting in cumulative mutations that push the infected cell along the multi‐step pathway to neoplasia. Tumour formation is a rare complication of these common viral infections and is determined by a combination of host, viral, and environmental factors. Viruses have crystallised current concepts in cancer biology and their involvement in human tumours has led to the development of vaccination strategies that aim to reduce the worldwide cancer burden attributed to these viruses.