tbuckley/cabot-search huggingface dataset:
Supportive evidence for a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis
Authors: K Ikari, S Momohara, T Nakamura, M Hara, H Yamanaka, T Tomatsu, N Kamatani
Journal: Annals of the Rheumatic Diseases (2005)

An association between susceptibility to rheumatoid arthritis and the Fc receptor-like 3 gene (FCRL3) has been reported in a Japanese population. A case-control study showed that the strongest evidence of the association was derived from a polymorphism in the promoter region of FCRL3, which has a regulatory effect on the expression of the gene.To validate the findings of this previous report by examining the -169C-->T single nucleotide polymorphism (SNP) in a large cohort.752 unrelated cases and 940 controls were genotyped. All the samples were from the same ethnic background as the original study. Genotyping was done using 5' allelic discrimination assays. Association between susceptibility to rheumatoid arthritis and -169C-->T SNP was examined by chi(2) testing.As in the previous study, the SNP showed significant differences between cases and controls (p = 0.022, odds ratio = 1.18, 95% confidence interval 1.02 to 1.35).This result supports a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis.
Perforin-dependent direct cytotoxicity in natural killer cells induces considerable knockdown of spontaneous lung metastases and computer modelling-proven tumor cell dormancy in a HT29 human colon cancer xenograft mouse model
Authors: Tobias Brodbeck, Nina Nehmann, Anja Bethge, Gero Wedemann, Udo Schumacher
Journal: Molecular Cancer (2014)

For long, natural killer (NK) cells have been suspected to play a critical role in suppressing the development of spontaneous metastases in cancer patients. Despite a wide range of studies it remains unclear so far to what extent primary tumor growth together with formation of distant metastases and NK cell activity influence each other. To precisely investigate the role of NK cells with a perforin-deficiency in cancer growth and metastasis formation, human HT29 colon cancer cells were subcutaneously grafted into pore forming protein and recombination activating gene 2 double knock out (pfp/rag2) mice and in recombination activating gene 2 only knock out (rag2) mice both with black six background. Both mice lack B and T cell functions due to the absence of rag2. Primary tumors developed in 16/16 in pfp/rag2 and 20/20 rag2 mice. At sacrifice primary tumor weight did not differ significantly. However, tumors grew faster in pfp/rag2 mice (50 days) than in pfp/rag2 mice (70 days). Circulating tumor cells (CTC) in murine blood were nearly three times higher in pfp/rag2 (68 cells/ml) than in rag2 mice (24 cells/ml). Lung metastases occurred frequently in pfp/rag2 mice (13/16) and infrequently in rag2 mice (5/20). The mean number of metastases was 789 in pfp/rag2 mice compared to 210 in rag2 mice. Lung metastases in pfp/rag2 mice consisted of 10–100 tumor cells while those in rag2 mice were generally disseminated tumor cells (DTCs). Computer modelling showed that perforin-dependent killing of NK cells decelerates the growth of the primary tumour and kills 80% of CTCs. Furthermore, perforin-mediated cytotoxicity hampers the proliferation of the malignant cells in host tissue forcing them to stay dormant for at least 30 days. The results exactly quantified the effect of perforin-dependent direct cytotoxicity of NK cells on HT29 on primary tumor growth, number of CTCs in the blood and the number of metastases. The largest effects were seen in the number of mice developing spontaneous lung metastases and the mean number of lung metastases. Hence, perforin-mediated cytotoxicity used for direct killing by NK cells is more important than indirect killing by secretion of death-inducing ligands by NK cells.
Omega 3 fatty acids and cardiovascular disease--fishing for a natural treatment
Authors: J. N Din
Journal: BMJ (2004)

Omega 3 fatty acids from fish and fish oils can protect against coronary heart disease. Both health professionals and the public are increasingly interested in their role in the prevention and management of coronary heart disease. In this era of multiple pharmacological treatments for cardiovascular disease many believe that simple dietary interventions or nutritional supplements may be a more natural and acceptable method of providing benefits. Several areas of uncertainty remain. The optimal intake of omega 3 fatty acids is not firmly established, nor is their mechanism of action fully understood. Some studies have produced conflicting results, and concerns have been increasing about environmental contamination of certain fish. This article reviews the current evidence regarding fish oils and cardiovascular disease, their possible mechanism of action, and potential future developments and research strategies.
β1 Integrins Are Critically Involved in Neutrophil Locomotion in Extravascular Tissue In Vivo
Authors: Joachim Werr, Xun Xie, Per Hedqvist, Erkki Ruoslahti, Lennart Lindbom
Journal: The Journal of Experimental Medicine (1998)

Recruitment of leukocytes from blood to tissue in inflammation requires the function of specific cell surface adhesion molecules. The objective of this study was to identify adhesion molecules that are involved in polymorphonuclear leukocyte (PMN) locomotion in extravascular tissue in vivo. Extravasation and interstitial tissue migration of PMNs was induced in the rat mesentery by chemotactic stimulation with platelet-activating factor (PAF; 10−7 M). Intravital time-lapse videomicroscopy was used to analyze migration velocity of the activated PMNs, and the modulatory influence on locomotion of locally administered antibodies or peptides recognizing various integrin molecules was examined. Immunofluorescence flow cytometry revealed increased expression of α4, β1, and β2 integrins on extravasated PMNs compared with blood PMNs. Median migration velocity in response to PAF stimulation was 15.5 ± 4.5 μm/min (mean ± SD). Marked reduction (67 ± 7%) in motility was observed after treatment with mAb blocking β1 integrin function (VLA integrins), whereas there was little, although significant, reduction (22 ± 13%) with β2 integrin mAb. Antibodies or integrin-binding peptides recognizing α4β1, α5β1, or αvβ3 were ineffective in modulating migration velocity. Our data demonstrate that cell surface expression of β1 integrins, although limited on blood PMNs, is induced in extravasated PMNs, and that members of the β1 integrin family other than α4β1 and α5β1 are critically involved in the chemokinetic movement of PMNs in rat extravascular tissue in vivo.
Response to Comments on Zhang et al. Second-Line Agents for Glycemic Control for Type 2 Diabetes: Are Newer Agents Better? Diabetes Care 2014;37:1338–1345
Authors: Yuanhui Zhang, Rozalina G. McCoy, Jennifer E. Mason, Steven A. Smith, Nilay D. Shah, Brian T. Denton
Journal: Diabetes Care (2014)

We are grateful for the comments from Messori and Bellia (1) and those of Bae et al. (2) regarding our article (3). We hope the following response will clarify the questions they raised.

Messori and Bellia (1) pointed out that the incremental cost-effectiveness ratio (ICER) is preferred over the absolute cost-effectiveness ratio. We agree, and it is worth noting that Fig. 1 in our article provides complete details about the expected quality-adjusted life-years (QALYs) prior to first events and the expected medication costs under all treatment regiments. As such, it subsumes ICER estimates. Admittedly, the readers must calculate them from the graph and therefore we provide the estimates for the glycemic control goal of HbA1c <7% here. For males, for regimens T1-T4 the ICERs in units of $/QALY are 10,369, 11,062, 11,277, 11,144, respectively. For females, for regimens T1-T4 the ICERs are 9,310, 9,865, 10,043, 9,933, respectively.

Messori …
Drug resistance among infantile enteropathogenic Escherichia coli strains isolated in the United Kingdom.
Authors: R J Gross, L R Ward, E J Threlfall, H King, B Rowe
Journal: BMJ (1982)

Two hundred and thirty-two strains of Escherichia coli belonging to infantile enteropathogenic serotypes isolated in the United Kingdom during 1980 and 1981 were tested for resistance to 10 antimicrobial drugs. Resistance to one or more drugs was found in 134 (57.8%) of the strains, with resistance to sulphonamides, streptomycin, tetracycline, and ampicillin occurring most commonly. Resistance was transferable in 65 out of 104 resistant strains. These findings are a cause for concern because they indicate that the choice of treatment for severe illness is limited and suggest that a large pool of drug-resistant organisms exists in the community.
Long-term Prospective Population PK Study in GIST Patients—Letter
Authors: Etienne Chatelut, Peggy Gandia, Verena Gotta, Nicolas Widmer
Journal: Clinical Cancer Research (2013)

The study conducted by Eechoute and colleagues ([1][1]) revealed additional and useful information regarding imatinib pharmacokinetics. By accumulating plasma imatinib concentrations in 50 patients for 12 months, they observed significantly lower concentrations after 90 days of treatment. It was
The pattern of use of mouthguards in rugby league (a study of the 1986 Australian Rugby League touring team).
Authors: P J Chapman
Journal: British Journal of Sports Medicine (1988)

Generally speaking, in contact sports the higher the grade of competition the greater the risk of a player sustaining any type of injury. Therefore it is important to conduct studies periodically of international sporting teams from different countries to detect any changes in regional injury patterns, besides assessing attitudes to the use of available protective equipment. A study of the prevalence of orofacial injuries and use of mouthguards by members of the 1984 Great Britain Rugby League Touring Team has previously been reported (Chapman, 1985a). In order to obtain a suitable basis for comparison of those results, a similar study of the members of the 1986 Australian Rugby League Touring Team to Great Britain was conducted. The most important finding was the much higher usage rate of mouthguards by the Australian footballers when compared with the British figure. Results of the study also support the function of mouthguards in reducing the incidence of orofacial injuries in contact sports.
Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans
Authors: Yutaka Hasegawa, Tokuo Saito, Takehide Ogihara, Yasushi Ishigaki, Tetsuya Yamada, Junta Imai, Kenji Uno, Junhong Gao, Keizo Kaneko, Tatsuo Shimosawa, Tomoichiro Asano, Toshiro Fujita, Yoshitomo Oka, Hideki Katagiri
Journal: Circulation (2012)

Nuclear factor-κB (NF-κB) signaling plays critical roles in physiological and pathological processes such as responses to inflammation and oxidative stress.To examine the role of endothelial NF-κB signaling in vivo, we generated transgenic mice expressing dominant-negative IκB under the Tie2 promoter/enhancer (E-DNIκB mice). These mice exhibited functional inhibition of NF-κB signaling specifically in endothelial cells. Although E-DNIκB mice displayed no overt phenotypic changes when young and lean, they were protected from the development of insulin resistance associated with obesity, whether diet- or genetics-induced. Obesity-induced macrophage infiltration into adipose tissue and plasma oxidative stress markers were decreased and blood flow and mitochondrial content in muscle and active-phase locomotor activity were increased in E-DNIκB mice. In addition to inhibition of obesity-related metabolic deteriorations, blockade of endothelial NF-κB signaling prevented age-related insulin resistance and vascular senescence and, notably, prolonged life span. These antiaging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity, and aortic upregulation of mitochondrial sirtuin-related proteins.The endothelium plays important roles in obesity- and age-related disorders through intracellular NF-κB signaling, thereby ultimately affecting life span. Endothelial NF-κB signaling is a potential target for treating the metabolic syndrome and for antiaging strategies.
MicroRNAs and Metastasis: Little RNAs Go a Long Way
Authors: Derek M. Dykxhoorn
Journal: Cancer Research (2010)

Abstract MicroRNAs (miRNA) are key regulators of many important biological processes from insulin secretion and fat metabolism to cellular proliferation and differentiation. Given the critical role that these small regulatory RNAs play in biology, it is not surprising that the alteration of miRNA expression patterns can have pathogenic consequences. The association between miRNA dysregulation and pathogenesis has been most widely studied in tumorigenesis, and a large number of miRNAs have been identified whose expression levels are changed in various tumor types. Although the role that miRNAs play in the development of metastasis is more poorly defined, recent studies have begun to identify miRNAs that can regulate key steps in the metastatic cascade. This review focuses on two emerging stories, the regulation of the epithelial-to-mesenchymal transition by members of the miR-200 family, and the pleiotropic nature of the metastasis suppressor miR-31. Cancer Res; 70(16); 6401–6. ©2010 AACR.
Population Pharmacokinetic-Pharmacodynamic Model of the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid in Cancer Patients
Authors: Jing Li, Michael B. Jameson, Bruce C. Baguley, Roberto Pili, Sharyn D. Baker
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To develop a population pharmacokinetic-pharmacodynamic (PK-PD) model that defines the dose-concentration-effect relationship of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), using plasma 5-hydroxyindole-3-acetic acid (5-HIAA) as a biomarker for the antivascular effect of DMXAA. Experimental Design: The plasma DMXAA and 5-HIAA concentration data were obtained from 124 patients receiving DMXAA monotherapy as a 20-minute i.v. infusion weekly or every 3 weeks at doses of 6 to 4,900 mg/m2. The PK and PD data were analyzed by nonlinear mixed effects modeling with NONMEM version 5. Results: DMXAA concentration-time profiles were well described by a three-compartment model with saturable elimination (Michaelis-Menten kinetics). Body surface area (BSA) and sex were significant covariates on the volume of distribution of the central compartment (V1) and the maximum elimination rate (Vm), respectively. Population estimates for Vm, Km (concentration at which half Vm is achieved), and V1 were 112[1 + 0.474(2 − sex)] μmol/L/h, 102 μmol/L, and 8.19(BSA/1.8)0.857 liters, respectively (sex in Vm is equal to 1 for males and equal to 2 for females). The effect of DMXAA on plasma 5-HIAA was described by the stimulatory Emax model, where population estimates for baseline, Emax, and EC50 were 46.3 μmol/L, 2.62-fold increase of the baseline value, and 631 μmol/L, respectively. Conclusions: DMXAA plasma disposition is characterized by a saturable elimination process. BSA-guided dosing is important. The present PK-PD model, with 5-HIAA as a biomarker, supports the use of DMXAA doses of 1,000 to 2,000 mg/m2 in phase II studies, and provides an example of how PK-PD models can be used to aid in selection of drug doses for phase II evaluation.
Opportunities for Control of Meningococcal Disease in the United States
Authors: Pratima L. Raghunathan, Scott A. Bernhardt, Nancy E. Rosenstein
Journal: Annual Review of Medicine (2004)

The United States currently has relatively low rates of meningococcal disease caused by Neisseria meningitidis. Serogroups Y, C, and B are most common. Although most cases are sporadic, a minority are associated with outbreaks. Pediatric populations have disproportionately higher rates of disease, but nearly two thirds of all cases occur in persons aged 15 years and older. The major challenge to control of domestic meningococcal disease is the absence of a vaccine to prevent sporadic cases spanning many age groups. The quadrivalent A/C/Y/W-135 meningococcal polysaccharide vaccine is licensed in the United States, but because of its limited efficacy in children under two years of age, it is recommended for high-risk groups and outbreak response rather than routine childhood immunization. New conjugate meningococcal vaccines have successfully reduced endemic disease in the United Kingdom, and similar vaccines promise to have a dramatic impact on the burden of meningococcal disease in the United States.
Efficacy of Routine Screening and Lateral Chest Radiographs in a Hospital-Based Population
Authors: Stuart S. Sagel, Ronald G. Evens, John V. Forrest, Robert T. Bramson, Rexford E. Hill, Bettye J. Thomas, Baruch E. Kahana
Journal: New England Journal of Medicine (1974)

A prospective study of chest roentgenographic examinations was conducted to determine if the elimination of some examinations or films often routinely obtained might be medically and economically justifiable. Analysis of data from over 10,000 examinations suggests that routine screening chest radiographs, obtained solely because of hospital admission or scheduled surgery, are not warranted in patients under 20; the lateral projection, which can be eliminated from routine screening examinations in patients 20 to 39 years of age, should be part of the chest roentgenographic examination whenever chest disease or a reasonable possibility of chest disease is suspected, and in screening examinations of patients 40 years of age or older. (N Engl J Med 291:1001–1004, 1974)
Premigratory risk factors in Vietnamese Amerasians
Authors: R S McKelvey, J A Webb, A R Mao
Journal: American Journal of Psychiatry (1993)

The study's goal was to determine the ability of risk factors determined before migration to predict future levels of anxiety and depression in a group of Vietnamese Amerasian immigrants.In a cohort of 161 randomly selected Vietnamese Amerasian youth in Vietnam awaiting placement, risk factors for psychological distress were identified with Felsman's 35-item Personal Information Form and the Hopkins Symptom Checklist-25 (HSCL-25). Ninety-five members of the original cohort were subsequently reevaluated, again with the HSCL-25, at a Philippine refugee center during their 6-month stay there awaiting placement in the United States.A statistically significant relationship was found between greater numbers of risk factors identified in Vietnam and higher total symptom levels in the Philippines. The strongest relationship was between greater numbers of risk factors and higher levels of depression. The relationship between number of risk factors and levels of anxiety was not significant.This study demonstrates the ability of risk factors determined prior to departure in Vietnam to predict future levels of psychological distress in a group of Vietnamese Amerasian immigrants.
Inhibition of Allergic Bronchial Asthma by Thrombomodulin Is Mediated by Dendritic Cells
Authors: Takehiro Takagi, Osamu Taguchi, Masaaki Toda, Daniel Boveda Ruiz, Paloma Gil Bernabe, Corina N D'Alessandro-Gabazza, Yasushi Miyake, Tetsu Kobayashi, Shinya Aoki, Fumiko Chiba, Yutaka Yano, Edward M Conway, Seiichi Munesue, Yasuhiko Yamamoto, Hiroshi Yamamoto, Koji Suzuki, Yoshiyuki Takei, John Morser, Esteban C Gabazza
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

bronchial asthma is caused by inappropriate acquired immune responses to environmental allergens. It is a major health problem, with a prevalence that is rapidly increasing. Curative therapy is not currently available.to test the hypothesis that thrombomodulin (TM) inhibits allergic bronchial asthma by inducing tolerogenic dendritic cells (DCs).the protective effect of TM was evaluated using a murine asthma model. Asthma was induced in mice by exposure to chicken egg ovalbumin, and the effects of inhaled TM or TM-treated DCs were assessed by administering before ovalbumin exposure.treatment with TM protects against bronchial asthma measured as improved lung function and reduced IgE and cells in alveolar lavage fluid by inducing tolerogenic dendritic dells. These are characterized by high expression of surface TM (CD141/TM(+)) and low expression of maturation markers and possess reduced T-cell costimulatory activity. The CD141/TM(+) DCs migrate less toward chemokines, and after TM treatment there are fewer DCs in the draining lymph node and more in the lungs. The TM effect is independent of its role in coagulation. Rather, it is mediated via the TM lectin domain directly interacting with the DCs.the results of this study show that TM is a modulator of DC immunostimulatory properties and a novel candidate drug for the prevention of bronchial asthma in atopic patients.
Prevalence of gallbladder disease in American Indian populations: Findings from the Strong Heart Study
Authors: James E. Everhart, Fawn Yeh, Elisa T. Lee, Michael C. Hill, Richard Fabsitz, Barbara V. Howard, Thomas K. Welty
Journal: Hepatology (2002)

American Indians are believed to be at high risk of gallbladder disease (GBD), but there has been no systematic evaluation of its prevalence among diverse groups of American Indians. Therefore, we determined the prevalence of GBD and associated risk factors among specified American Indian populations using ultrasonography of the gallbladder and standardized diagnostic criteria. Enrolled members, aged 47 years and older, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota who participated in the Strong Heart Study were analyzed. GBD was the sum of gallstones (determined by ultrasound examination) and cholecystectomy (determined by ultrasound and self-report). The proportion of American Indian heritage was based on the heritage of the grandparents of participants. GBD prevalence was determined among 3,296 participants at the 3 sites. Among women, 17.8% had gallstones, and 46.3% had evidence of a cholecystectomy, for a total of 64.1% with GBD. Among men, 17.4% had gallstones, and 12.1% had evidence of a cholecystectomy, for a total of 29.5% with GBD. When figures were adjusted for age and Indian heritage, there was no significant difference in GBD prevalence across the 3 geographical areas. In multivariate logistic regression analysis, age, American Indian heritage, and waist circumference were associated with GBD among men, and age, American Indian heritage, diabetes, and parity were associated with GBD among women. Body mass index was not independently associated with GBD in either sex. In conclusion, GBD was found in epidemic proportions in diverse American Indian populations.
Reactive lymphoid hyperplasia of the liver
Authors: Woo Sung Moon, Keum Ha Choi
Journal: Clinical and Molecular Hepatology (2013)

Reactive lymphoid hyperplasia (RLH) is a rare benign condition that forms a mass-like lesion characterized by proliferation of non-neoplastic lymphocytes forming follicles and germinal centers. RLH is thought to represent a reactive immunological response, and some cases may arise in association with malignancy and hepatitis.1 Radiologically, RLH of the liver may mimic a primary or metastatic hepatic malignancy. Therefore, it is very difficult to diagnose correctly without pathological examination. In this issue, we present a case of hepatic RLH and discuss the histopathologic findings with a review of the literatures.