tbuckley/cabot-search huggingface dataset:
Sensitization of cervix cancer cells to Adriamycin by Pentoxifylline induces an increase in apoptosis and decrease senescence
Authors: Alejandro Bravo-Cuellar, Pablo C Ortiz-Lazareno, Jose M Lerma-Diaz, Jorge R Dominguez-Rodriguez, Luis F Jave-Suarez, Adriana Aguilar-Lemarroy, Susana del Toro-Arreola, Ruth de Celis-Carrillo, Jose E Sahagun-Flores, Javier E Garcia de Alba-Garcia, Georgina Hernandez-Flores
Journal: Molecular Cancer (2010)

Chemotherapeutic drugs like Adriamycin (ADR) induces apoptosis or senescence in cancer cells but these cells often develop resistance and generate responses of short duration or complete failure. The methylxantine drug Pentoxifylline (PTX) used routinely in the clinics setting for circulatory diseases has been recently described to have antitumor properties. We evaluated whether pretreatment with PTX modifies apoptosis and senescence induced by ADR in cervix cancer cells.HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non-tumorigenic immortalized HaCaT cells (control) were treated with PTX, ADR or PTX + ADR. The cellular toxicity of PTX and survival fraction were determinated by WST-1 and clonogenic assay respectively. Apoptosis, caspase activation and ADR efflux rate were measured by flow cytometry, senescence by microscopy. IkappaBalpha and DNA fragmentation were determinated by ELISA. Proapoptotic, antiapoptotic and senescence genes, as well as HPV-E6/E7 mRNA expression, were detected by time real RT-PCR. p53 protein levels were assayed by Western blot.PTX is toxic (WST-1), affects survival (clonogenic assay) and induces apoptosis in cervix cancer cells. Additionally, the combination of this drug with ADR diminished the survival fraction and significantly increased apoptosis of HeLa and SiHa cervix cancer cells. Treatments were less effective in HaCaT cells. We found caspase participation in the induction of apoptosis by PTX, ADR or its combination. Surprisingly, in spite of the antitumor activity displayed by PTX, our results indicate that methylxantine, per se does not induce senescence; however it inhibits senescence induced by ADR and at the same time increases apoptosis. PTX elevates IkappaBalpha levels. Such sensitization is achieved through the up-regulation of proapoptotic factors such as caspase and bcl family gene expression. PTX and PTX + ADR also decrease E6 and E7 expression in SiHa cells, but not in HeLa cells. p53 was detected only in SiHa cells treated with ADR.PTX is a good inducer of apoptosis but does not induce senescence. Furthermore, PTX reduced the ADR-induced senescence and increased apoptosis in cervix cancer cells.
Pulmonary and liver injury after exposure to sublethal doses of microcystin-LR
Authors: Walter Zin, Giovanna Carvalho, Vinicius Oliveira, Natalia Casquilho, Raquel Soares, Sandra Azevedo, Karla Pires, Samuel Valença
Journal: European Respiratory Journal (2011)

Rationale:  Biological pollution caused by cyanotoxins leads to respiratory function impairment.   Aim:  Study pulmonary mechanics, lung and liver histology in mice submitted to sublethal doses of microcystin-LR (MCLR) and evaluate whether the results depended on the doses.   Methods:  Male Swiss mice were divided into 2 groups: CTRL (n=6) received distilled water intraperitoneally (ip, 100 mL) and TOX (n=30): injected with sublethal doses of MCLR (5, 10, 15, 20 and 25 μg/kg ip in 100 mL of distilled water). 24 h later pulmonary mechanics [static elastance (Est), viscoelastic component of elastance (ΔE), resistive (ΔP1), viscoelastic (ΔP2), and total (ΔPtot) pressures] were determined, and lungs and livers were prepared for histopathology. ANOVA was used to test differences among the groups.   Results: Δ P2, ΔE and ΔPtot were significantly higher than CTRL in all MCLR doses, but did not differ among them. Only TOX25 showed significantly higher Est and ΔP1 than CTRL. Alveolar collapse was higher in TOX10 (18.95%), TOX15 (17.56%), TOX20 (19.11%) and TOX25 (21.63%) than in CTRL (11.57%). The lung inflammatory cell content (cells/μm 2 ) gradually increased: TOX10=2.90×10 -3 , TOX15=4.96×10 -3 , TOX20=5.46×10 -3  and TOX25= 5.03×10 -3  in relation to CTRL=1.41×10 -3 . All TOX mice showed a complete loss of liver architecture with hyalinization, steatosis, dilated sinusoidal spaces and a high degree of binucleated hepatocytes. Necrosis began in TOX15, whereas only TOX 25 showed inflammation.   Conclusion:  MCLR impaired pulmonary mechanics, lung and liver histology. These findings depended on the degree of exposure.  Supported by: FAPERJ, CNPq, MCT
Association between Chronic Atrophic Gastritis and Serum Antibodies to 15 <i>Helicobacter pylori</i> Proteins Measured by Multiplex Serology
Authors: Lei Gao, Melanie N. Weck, Angelika Michel, Michael Pawlita, Hermann Brenner
Journal: Cancer Research (2009)

Infection with Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG), a precursor lesion of intestinal gastric cancer. The pathogenicity of the bacterium is thought to play an important role in determining the extent and severity of clinical outcome. We aimed to assess the associations between CAG and the serostatus of antibodies to 15 H. pylori proteins. The analyses were based on 534 cases with serologically defined CAG and 1,068 age-matched and sex-matched controls participating in a population-based study conducted in Saarland, Germany among 9,953 men and women ages 50 to 74 years. A newly developed H. pylori multiplex serology method was used to detect antibodies specific to 15 H. pylori antigens. Significant associations were observed between seropositivity for all 15 specific antibodies and the presence of CAG. Exclusion of severe cases, who might have lost the infection in the course of CAG progression, substantially increased the observed associations. In H. pylori-seropositive subjects, cytotoxin-associated gene A (CagA), vacuolating toxin (VacA), helicobacter cysteine-rich protein C (HcpC), and the chaperonin GroEL were identified as independent virulence factors for CAG with adjusted odds ratios (95% confidence interval) of 3.52 (2.01-6.10), 3.19 (1.44-7.05), 4.03 (1.53-10.65), and 2.65 (1.06-6.62), respectively; the simultaneous presence of all four independent virulence factors was associated with an 18-fold risk of CAG. In conclusion, HcpC and GroEL were identified as new independent virulence factors, and in combination with the established virulence factors, CagA and VacA, were strongly associated with CAG.
Trends in <i>Haemophilus influenzae</i> type b infections in adults in England and Wales: surveillance study
Authors: Jodie McVernon, Caroline L Trotter, Mary P E Slack, Mary E Ramsay
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To describe invasive <i>Haemophilus influenzae</i> type b (Hib) infections in individuals aged 15 years or older in England and Wales between 1991 and 2003. <b>Design</b> Prospective, laboratory based surveillance of invasive Hib infections and cross sectional seroprevalence study. <b>Setting</b> England and Wales. <b>Participants</b> Cases were confirmed by isolation of <i>H influenzae</i> from a normally sterile site, or from a non-sterile site in cases with a diagnosis of epiglottitis. Excess serum samples collected from English 30-39 year olds as part of a national serosurvey were identified for the years 1990, 1994, 1997, 2000, and 2002. <b>Main outcome measures</b> The number of invasive Hib infections from 1991 to 2003. Population immunity to <i>H influenzae</i> type b in English adults was also measured. <b>Results</b> After routine infant immunisation was introduced in October 1992, adult Hib infections decreased initially but then rose from a low in 1998 to reach prevaccine levels in 2003. An associated fall in median Hib antibody concentrations occurred, from 1.29 µg/ml (95% confidence interval 0.90 to 1.64) in 1991 to 0.70 µg/ml (0.57 to 0.89) in 1994 (P = 0.006), with no significant change observed thereafter. <b>Conclusions</b> Although immunisation of infants resulted in an initial decline in Hib infections in adults, a resurgence in reported cases occurred in 2002-3. This rise was associated with an increase in cases in children and evidence of reduced immunity in older unimmunised cohorts. Childhood immunisation programmes may have unanticipated effects on the epidemiology of disease in older age groups, and surveillance strategies must be targeted at entire populations.
CD40 Ligand Is Not Essential for Induction of Type 1 Cytokine Responses or Protective Immunity after Primary or Secondary Infection With <i>Histoplasma capsulatum </i>
Authors: Ping Zhou, Robert A. Seder
Journal: The Journal of Experimental Medicine (1998)

The induction of type 1 immune responses (interleukin [IL]-12, interferon [IFN]-γ) has been shown to be important in mediating protection against many intracellular infections including Histoplasma capsulatum. Costimulatory molecules such as CD40 ligand (CD40L) have been shown to be a central regulator of type 1 responses in vivo. To study the role of CD40L in mediating protection against infection with H. capsulatum, CD40L-deficient (CD40L−/−) and CD40L+/+ mice were infected with H. capsulatum and assessed for various parameters. After a lethal challenge of H. capsulatum, CD40L−/− mice were not substantially different from CD40L+/+ mice in terms of mortality, fungal burden, or production of IFN-γ, IL-12, nitric oxide, or tumor necrosis factor α. Moreover, CD40L−/− mice treated with anti–IFN-γ or anti–IL-12 at the time of infection had accelerated mortality, providing further evidence that IL-12 and IFN-γ are produced in vivo in the absence of CD40L. In addition, CD40L−/− mice infected with a sublethal dose of H. capsulatum survived infection, whereas all mice infected with the same dose and treated with anti–IFN-γ had accelerated mortality, demonstrating that IFN-γ but not CD40L was essential for primary immunity to H. capsulatum infection. Interestingly, depletion of either CD4+ or CD8+ T cells resulted in accelerated mortality in CD40L−/− mice, suggesting a critical role for these cells in response to infection. Finally, CD40L−/− mice initially infected with a sublethal dose of H. capsulatum were protected from secondary infection with a lethal dose of H. capsulatum, demonstrating that CD40L is not required for the maintenance of memory immunity.
Treatment of ventilatory failure in the Prader-Willi syndrome
Authors: IE Smith, MA King, PW Siklos, JM Shneerson
Journal: European Respiratory Journal (1998)

Hypercapnic respiratory failure is a common cause of death in the Prader-Willi syndrome. Its relationship to sleep-disordered breathing has not been established and there are no reports of its successful treatment. We have retrospectively reviewed the records of four patients with the syndrome, who developed ventilatory failure. Daytime arterial blood gas tensions and overnight oximetry traces before and during treatment were compared. Each patient had severe sleep-disordered breathing in association with daytime ventilatory failure. The median overnight mean arterial oxygen saturation (Sa,O2) was 82% and the median minimum was only 41.5%. Initial treatment was with nasal intermittent positive pressure ventilation, and in each case the daytime arterial blood gas tensions were normalized. The patients were maintained on nasal continuous positive airway pressure at night after discharge. Compliance has been good, and at last follow-up (after a median of 4.8 yrs) the daytime arterial gas tensions remained normal, while the median overnight mean arterial oxygen saturation was 95.5% and the median minimum was 84.5%. This study of patients with the Prader-Willi syndrome shows that daytime ventilatory failure is associated with sleep-disordered breathing. It can be reversed with nocturnal noninvasive ventilation and maintenance treatment with continuous positive airway pressure is well tolerated, with no deterioration in respiratory parameters.
Paraneoplastic neurological syndrome and polyglandular autoimmune syndrome type 2 in a case of small cell lung cancer
Authors: S Watanabe, J Tanaka, T Ohta, H Yoshizawa, F Gejyo
Journal: Thorax (2008)

We report a female patient with small cell lung cancer (SCLC) and clinical findings consistent with polyglandular autoimmune syndrome type 2 (PGA2) and paraneoplastic neurological syndrome (PNS). To the best of our knowledge, this is the first reported case of SCLC associated with PGA2 and PNS. All of the autoantibodies detected before anticancer treatment decreased below the upper normal limits after serial treatment, and the patient’s clinical symptoms also improved. Cross reactivity of autoantibodies may have contributed to the complicated clinical picture of this patient.
The Alcohol Hangover
Authors: Jeffrey G. Wiese, Michael G. Shlipak, Warren S. Browner
Journal: Annals of Internal Medicine (2000)

Purpose: To review the cause, pathophysiologic characteristics, cost, and treatment of alcohol-induced hangover. Data Sources: A MEDLINE search of English-language reports (1966 to 1999) and a manual search of bibliographies of relevant papers. Study Selection: Related experimental, clinical, and basic research studies. Data Extraction: Data in relevant articles were reviewed, and relevant clinical information was extracted. Data Synthesis: The alcohol hangover is characterized by headache, tremulousness, nausea, diarrhea, and fatigue combined with decreased occupational, cognitive, or visual–spatial skill performance. In the United States, related absenteeism and poor job performance cost $148 billion annually (average annual cost per working adult, $2000). Although hangover is associated with alcoholism, most of its cost is incurred by the light-to-moderate drinker. Patients with hangover may pose substantial risk to themselves and others despite having a normal blood alcohol level. Hangover may also be an independent risk factor for cardiac death. Symptoms of hangover seem to be caused by dehydration, hormonal alterations, dysregulated cytokine pathways, and toxic effects of alcohol. Physiologic characteristics include increased cardiac work with normal peripheral resistance, diffuse slowing on electroencephalography, and increased levels of antidiuretic hormone. Effective interventions include rehydration, prostaglandin inhibitors, and vitamin B6. Screening for hangover severity and frequency may help early detection of alcohol dependency and substantially improve quality of life. Recommended interventions include discussion of potential therapies and reminders of the possibility for cognitive and visual–spatial impairment. No evidence suggests that alleviation of hangover symptoms leads to further alcohol consumption, and the discomfort caused by such symptoms may do so. Therefore, treatment seems warranted. Conclusions: Hangover, a common disorder, has substantial morbidity and societal cost. Appropriate management may relieve symptoms in many patients.
T−B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3ζ subunit of the T-cell antigen receptor complex
Authors: Joseph L. Roberts, Jens Peter H. Lauritsen, Myriah Cooney, Roberta E. Parrott, Elisa O. Sajaroff, Chan M. Win, Michael D. Keller, Jeffery H. Carpenter, Juan Carabana, Michael S. Krangel, Marcella Sarzotti, Xiao-Ping Zhong, David L. Wiest, Rebecca H. Buckley
Journal: Blood (2006)
Met acts through Abl to regulate p53 transcriptional outcomes and cell survival in the developing liver
Authors: Alessandro Furlan, Fabienne Lamballe, Venturina Stagni, Azeemudeen Hussain, Sylvie Richelme, Andrea Prodosmo, Anice Moumen, Christine Brun, Ivan del Barco Barrantes, J. Simon C. Arthur, Anthony J. Koleske, Angel R. Nebreda, Daniela Barilà, Flavio Maina
Journal: Journal of Hepatology (2012)
IMPACT ATTENUATION OF PROTECTIVE BOXING AND TAEKWONDO HEADGEAR
Authors: D O'Sullivan, G Fife, W Pieter
Journal: British Journal of Sports Medicine (2014)

Background To date, only one study reported the impact attenuation of protective taekwondo headgear. Although Olympic boxing has discontinued the use of headgear, similarities in designs are thought to provide a framework for improvements of taekwondo headgear. Objective To determine differences in impact attenuation of taekwondo and boxing headgear. Design Between groups. Setting Impact biomechanics laboratory. Participants World Taekwondo Federation (WTF) and Amateur International Boxing Association (AIBA) approved protective headgear. Risk factor assessment A standardized (ASTM F-2397) martial arts headgear striker was used to impart impacts to a 50th Percentile Male Hybrid III Dummy head and neck complex. All impacts were imparted with a terminal striking velocity of 5.0 m/s (min - max=4.75 −5.15m/s). 2 AIBA-approved headgear (Adidas and Green Hills) and 2 WTF-approved headgear were selected for testing. Each headgear model was fitted to the Hybrid III and impacted a total of 5 times to the left side (temporal) of the headgear along an ASTM-specified impact region. As per ASTM standards low velocity impacts must yield head RLAs below 50g. Main outcome measurements Resultant linear acceleration (RLA). Results 1-way ANOVA showed significant differences between the headgear brands (eta 2 =0.928). The most protection was provided by the taekwondo Adidas headgear (60.5±4.3g) followed by the boxing Adidas (75.4±9.9g), boxing Greenhill (109.4±10.11g), and taekwondo Nike headgear (129.5±8.2g). The greatest difference in RLA was observed between the two taekwondo models (d=−9.54, 95% CI=−13.91 – −5.18), whereas the smallest clinically meaningful difference was observed between the two Adidas models (d=−1.94, 95% CI=−3.20 – −0.29). Conclusions Each of the headgear brands performed differently under the testing conditions. All models need to be redesigned to mitigate low velocity impacts. Future testing must include impacts at high impact velocities.
Children in Motor Vehicles
Authors: Jerome J. Karwacki
Journal: JAMA (1979)

In a series of 89 children less than 15 years old who were killed as motor vehicle occupants, children under 1 year of age were greatly overrepresented. Only three children were using child restraint systems or seat belts. Eight were traveling on their parents' laps. Head injuries predominated and were most common in the youngest children. Children under age 1 were the most likely to have reached the hospital alive. The high death rate for very young children was not explained by the circumstances of the crashes or by the age distribution of children involved in all crashes. (<i>JAMA</i>242:2848-2851, 1979)
Oxaliplatin reintroduction in patients previously treated with leucovorin, fluorouracil and oxaliplatin for metastatic colorectal cancer
Authors: F. Maindrault-Gœbel, C. Tournigand, T. André, E. Carola, M. Mabro, P. Artru, C. Louvet, A. de Gramont
Journal: Annals of Oncology (2004)
Response to: Effect of inhibition of Na+/Ca+ exchanger at the time of myocardial reperfusion on hypercontracture and cell death
Authors: S Anderson
Journal: Cardiovascular Research (2002)

ischemia in response to the increase in [Na] which results i issue.from increased uptake via such pathways as Na / H ex-The functional and biochemical characterization of the change [10].That is, increases in [Na] are more important
Customized Oligonucleotide Microarray Gene Expression–Based Classification of Neuroblastoma Patients Outperforms Current Clinical Risk Stratification
Authors: André Oberthuer, Frank Berthold, Patrick Warnat, Barbara Hero, Yvonne Kahlert, Rüdiger Spitz, Karen Ernestus, Rainer König, Stefan Haas, Roland Eils, Manfred Schwab, Benedikt Brors, Frank Westermann, Matthias Fischer
Journal: Journal of Clinical Oncology (2006)

To develop a gene expression-based classifier for neuroblastoma patients that reliably predicts courses of the disease.Two hundred fifty-one neuroblastoma specimens were analyzed using a customized oligonucleotide microarray comprising 10,163 probes for transcripts with differential expression in clinical subgroups of the disease. Subsequently, the prediction analysis for microarrays (PAM) was applied to a first set of patients with maximally divergent clinical courses (n = 77). The classification accuracy was estimated by a complete 10-times-repeated 10-fold cross validation, and a 144-gene predictor was constructed from this set. This classifier's predictive power was evaluated in an independent second set (n = 174) by comparing results of the gene expression-based classification with those of risk stratification systems of current trials from Germany, Japan, and the United States.The first set of patients was accurately predicted by PAM (cross-validated accuracy, 99%). Within the second set, the PAM classifier significantly separated cohorts with distinct courses (3-year event-free survival [EFS] 0.86 +/- 0.03 [favorable; n = 115] v 0.52 +/- 0.07 [unfavorable; n = 59] and 3-year overall survival 0.99 +/- 0.01 v 0.84 +/- 0.05; both P < .0001) and separated risk groups of current neuroblastoma trials into subgroups with divergent outcome (NB2004: low-risk 3-year EFS 0.86 +/- 0.04 v 0.25 +/- 0.15, P < .0001; intermediate-risk 1.00 v 0.57 +/- 0.19, P = .018; high-risk 0.81 +/- 0.10 v 0.56 +/- 0.08, P = .06). In a multivariate Cox regression model, the PAM predictor classified patients of the second set more accurately than risk stratification of current trials from Germany, Japan, and the United States (P < .001; hazard ratio, 4.756 [95% CI, 2.544 to 8.893]).Integration of gene expression-based class prediction of neuroblastoma patients may improve risk estimation of current neuroblastoma trials.
Antitumor Efficacy Testing in Rodents
Authors: Melinda G. Hollingshead
Journal: JNCI Journal of the National Cancer Institute (2008)

The preclinical research and human clinical trials necessary for developing anticancer therapeutics are costly. One contributor to these costs is preclinical rodent efficacy studies, which, in addition to the costs associated with conducting them, often guide the selection of agents for clinical development. If inappropriate or inaccurate recommendations are made on the basis of these preclinical studies, then additional costs are incurred. In this commentary, I discuss the issues associated with preclinical rodent efficacy studies. These include the identification of proper preclinical efficacy models, the selection of appropriate experimental endpoints, and the correct statistical evaluation of the resulting data. I also describe important experimental design considerations, such as selecting the drug vehicle, optimizing the therapeutic treatment plan, properly powering the experiment by defining appropriate numbers of replicates in each treatment arm, and proper randomization. Improved preclinical selection criteria can aid in reducing unnecessary human studies, thus reducing the overall costs of anticancer drug development.
Follicular Dendritic Cells Specifically Express the Long CR2/CD21 Isoform
Authors: Yong-Jun Liu, Jiangchun Xu, Odette de Bouteiller, Christi L. Parham, Géraldine Grouard, Odile Djossou, Blandine de Saint-Vis, Serge Lebecque, Jacques Banchereau, Kevin W. Moore
Journal: The Journal of Experimental Medicine (1997)

This paper describes an antibody (mAb 7D6) that specifically recognizes human follicular dendritic cells (FDCs). By expression cloning, a cDNA clone encoding for the long human CR2/ CD21 isoform (CD21L) that contains an additional exon (10a) was isolated. We demonstrated that FDCs selectively express CD21L, while B cells selectively express the short CR2/CD21 lacking exon 10a (CD21S). By screening mouse Ltk− cells transfected with the CD21L cDNA, we further showed that the other two anti–human FDC mAbs DRC-1 and KiM4 also recognize CD21L. Thus, CD21L represents the first characterized human FDC-specific molecule, which may confer unique functions of FDCs in germinal center development.