tbuckley/cabot-search huggingface dataset:
Serum Uric Acid
Authors: Daniel I. Feig, Marilda Mazzali, Duk-Hee Kang, Takahiko Nakagawa, Karen Price, John Kannelis, Richard J. Johnson
Journal: Journal of the American Society of Nephrology (2006)

Serum uric acid was first noted to be associated with increased BP by Frederick Mohamed in the 1870s. Although the link was rediscovered periodically over the years, it generally was dismissed as a surrogate marker for decreased renal function that led to increased uric acid and increased risk for hypertension and cardiovascular (CV) disease. Recently, however, several lines of evidence suggest that increased serum uric acid may be a significant modifiable risk factor. Increased serum uric acid is associated with increased risk for future hypertension in several large longitudinal clinical trials as well as an independent risk factor for poor CV prognosis. Animal model experiments demonstrate that increased serum uric acid causes increased BP that initially is reversible but becomes irreversible, salt sensitive, and uric acid independent over time. The mechanisms include the direct action of uric acid on smooth muscle and vascular endothelial cells. Finally, in adolescents with new-onset essential hypertension, the prevalence of elevated serum uric acid is >90%, and preliminary clinical trial evidence suggests that agents that lower serum uric acid may lower BP in this select population. Although the investigations are still preliminary, serum uric acid represents a possible new and intriguing target for the reduction of morbidity and mortality associated with hypertension and CV disease.
Lactose malabsorption and postgastrectomy milk intolerance, dumping, and diarrhoea.
Authors: J R Condon, P Westerholm, N C Tanner
Journal: Gut (1969)

In patients with deficient intestinal lactase activity there is decreased hydrolysis of ingested lactose into its constituent monosaccharides glucose and galac- tose, and abdominal distension, cramps, and diarrhoea may occur after the consumption of lactose-containing foods.Unhydrolysed lactose on August 6,
Youth Hate Crimes: Identification, Prevention, and Intervention
Authors: Annie Steinberg, Jane Brooks, Tariq Remtulla
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Youth hate crimes are a societal problem in which young people turn extremist ideas into acts of violence. To develop methods for prevention, early identification, and intervention, mental health professionals must have an awareness and understanding of this issue. To provide a basis for developing such an understanding, the authors review the current research related to youth hate crimes. METHOD: The authors review the literature primarily from the past 10 years on youth hate crimes. RESULTS: Studies have established that most hate crimes are committed by single or small groups of young males unaffiliated with organized hate groups. Although limited information is available about the causative factors of hatred, a variety of prevention and intervention strategies have been employed. Yet, little has been done to evaluate these various initiatives. Unfortunately, there is a paucity of literature available to guide mental health professionals in the identification, evaluation, and treatment of offenders, despite increasing concerns and awareness regarding the profound consequences of acts of hatred and extremism. CONCLUSIONS: Heightened public awareness and greater understanding of the epidemiology and nature of hate crimes is necessary if perpetrators are to be recognized and effective interventions developed. To achieve this goal, databases of juvenile hate crimes must be developed nationwide, and the success of preventive, educational, and alternative sentencing programs must be assessed. Mental health professionals play a critical role in the detection and treatment of juvenile perpetrators, and it is incumbent upon them to develop interventions for individuals and communities affected by hate crimes.
Measurement Error and Results From Analytic Epidemiology: Dietary Fat and Breast Cancer
Authors: R. L. Prentice
Journal: JNCI Journal of the National Cancer Institute (1996)

BackgroundInternational correlational analyses have suggested a strong positive association between fat consumption and breast cancer incidence, especially among post-menopausal women. However, case-control studies have been taken to indicate a weaker association, and a recent, pooled cohort analysis reported little evidence of an association. Differences among study results could be due to differences in the populations studied, differences in the control for total energy intake, recall bias in the case-control studies, and dietary measurement error biases. Existing measurement error models assume either that the sample data used to validate dietary self-report instruments are without measurement error or that any such error is independent of both the true dietary exposure and other study subject characteristics. However, growing evidence indicates that total energy and, presumably, both total fat and percent energy from fat are increasingly underreported as percent body fat increases.
Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II
Authors: Hyota Takamatsu, Noriko Takegahara, Yukinobu Nakagawa, Michio Tomura, Masahiko Taniguchi, Roland H Friedel, Helen Rayburn, Marc Tessier-Lavigne, Yutaka Yoshida, Tatsusada Okuno, Masayuki Mizui, Sujin Kang, Satoshi Nojima, Tohru Tsujimura, Yuji Nakatsuji, Ichiro Katayama, Toshihiko Toyofuku, Hitoshi Kikutani, Atsushi Kumanogoh
Journal: Nature Immunology (2010)
Abstract P3-08-06: ROK study: Breast cancer survivorship cohort in Japan - Characteristics of 2,600 study participants
Authors: Y Mizota, S Yamamoto
Journal: Cancer Research (2013)

Abstract [Background] Although there is growing epidemiologic studies to investigate the etiological role of lifestyle factors and psychosocial factors on female breast cancer, few studies have examined the effect of these factors on breast cancer prognosis. To investigate the influence of lifestyle factors and psychosocial factors on prognosis including the quality of life, recurrence and survival of patients with breast cancer, we designed a large-scale cohort study of breast cancer patients in Japan. In our study, lifestyle factors include diet, physical activity, and use of complementary/alternative medicine, psychosocial factors include hope, perceived positive changes such as growth from breast cancer, depression, support and so on. [Methods] Our goal is recruiting 6,000 breast cancer patients. Main part of this study is being conducted as a collaborative study with three randomized clinical trials and one cancer registration. Participant's information on clinical factors, treatment, and follow-up will be obtained from the clinical trials and cancer registration. In addition, we started recruitment at National Cancer Hospital. A self-administered questionnaire will be delivered to participants before and every year (1 to 5 years) after surgery, and their responses will be employed as baseline data. At National Cancer Center Hospital blood samples and tissues are also to be collected. The primary endpoint is disease-free survival. The secondary endpoints are overall survival and the health-related quality of life. The follow-up period will be 5 years after the last participant enrollment. We will examine the association of lifestyle factors, psychosocial factors, biomarkers and genetic polymorphisms with the prognosis based on follow-up data. [Results] Recruitment began in November, 2007, and as of March, 2013, 2,655 women have been enrolled along with 2,591 questionnaire data, 236 blood samples and tissues. As it is now, approximately 50 women a month newly enrolled. Recruitment will be continued at least into 2018, the Rainbow of KIBOU Study will become one of the largest breast cancer cohorts in the world. In this presentation, we describe the study design and report baseline demographic among the study participants. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-06.
HISTOCOMPATIBILITY-LINKED IMMUNE RESPONSE GENE FUNCTION IN GUINEA PIGS
Authors: Ethan M. Shevach, William E. Paul, Ira Green
Journal: The Journal of Experimental Medicine (1972)

A number of autosomal dominant immune response (IR) genes have been identified in both mice and guinea pigs. These IR genes have been shown to be linked to the major histocompatibility antigens of the species and to be functionally expressed primarily in T lymphocytes. In order to more fully understand the relationship between IR genes, histocompatibility antigens, and immune recognition, the effect of specific alloantisera on lymphocyte stimulation induced by antigens under control of IR genes was examined. Using lymphocytes from strain 2 or strain 13 animals, the in vitro proliferative responses both to antigens which are known to be under genetic control (DNP-GL in strain 2 guinea pigs and GT in strain 13 guinea pigs) and to an antigen which is not known to be under genetic control (PPD) were inhibited to a similar degree and to a much greater extent than the response to phytohemagglutinin. However, when cells from F(1) (2 x 13) animals are used, the alloantisera markedly inhibit only the response which is linked to the histocompatibility antigens against which the serum is directed. Thus, the anti-2 serum inhibited the response to DNP-GL but not to GT; the anti-13 serum inhibited the response to GT but did not affect DNP-GL response. The inhibitory activity of the alloantisera could not be removed by absorption with gamma globulin of the opposite strain. It can be concluded from these observations that immune response genes produce a cell surface-associated product and that this product plays a role in the mechanism of antigen recognition by the T lymphocyte. The mechanisms by which alloantisera block this process of antigenic recognition is not resolved nor is the relationship between the IR gene product and the antigen-binding receptor of the T lymphocyte. The approach described here offers a powerful tool for the resolution of these problems.
Molecular Determinants of Cetuximab Efficacy
Authors: Daniel Vallböhmer, Wu Zhang, Michael Gordon, Dong Yun Yang, Jim Yun, Oliver A. Press, Katrin E. Rhodes, Andy E. Sherrod, Syma Iqbal, Kathleen D. Danenberg, Susan Groshen, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2005)

Purpose To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. Patients and Methods Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. Results There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. Conclusion This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.
Physiologically Assessed Coronary Collateral Flow and Intracoronary Growth Factor Concentrations in Patients With 1- to 3-Vessel Coronary Artery Disease
Authors: Martin Fleisch, Michael Billinger, Franz R. Eberli, Ali R. Garachemani, Bernhard Meier, Christian Seiler
Journal: Circulation (1999)

Background —The purpose of this study was to test the hypothesis that there is a relation between collateral flow and intracoronary concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) and that the combined concentrations of both growth factors and the extent of coronary artery disease (CAD) play a role as covariables in such an association. Methods and Results —In 76 patients undergoing balloon angioplasty, a collateral flow index (CFI, no units) was determined with sensor-tipped guidewires. Simultaneously, serum concentrations of bFGF and VEGF, obtained at the aortic root from the ostium of the collateralized coronary artery (n=76) and from the distal position of the occluded coronary artery (n=34), were determined. There was a direct correlation between CFI and distal VEGF ( r =0.33, P =0.05) but not bFGF concentrations. Focusing on the proximal sampling site, there was a direct correlation between CFI and both bFGF ( r =0.29, P =0.01) and VEGF concentrations ( r =0.44, P &lt;0.0001). The sum of the concentrations of both growth factors was directly associated with CFI irrespective of the proximal ( r =0.51, P &lt;0.0001) or distal sampling site ( r =0.34, P =0.048). There was a trend toward higher proximal VEGF concentrations in patients with higher numbers of coronary stenotic lesions ( r =0.25, P =0.03). Conclusions —In patients with CAD, there is an association between a directly measured index of collateral flow and intracoronary concentrations of bFGF and VEGF. This direct relation is dependent on the site of blood sampling within the coronary artery tree. The association is closest when the combined bFGF and VEGF concentrations are taken into account. In the case of VEGF, it is influenced by the degree of coronary atherosclerosis.
Bone Morphogenetic Proteins as Regulators of Iron Metabolism
Authors: Nermi L. Parrow, Robert E. Fleming
Journal: Annual Review of Nutrition (2014)

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-β) superfamily of signaling molecules. In addition to protean roles in embryonic development, germ-line specification, and cellular differentiation, a central role in iron homeostasis has recently been demonstrated for certain BMPs. Specifically, BMP6 serves to relate hepatic iron stores to the hepatocellular expression of the iron-regulatory hormone hepcidin. This regulation occurs via cellular SMAD-signaling molecules and is strongly modulated by the BMP coreceptor hemojuvelin (HJV). Mutations in certain genes influencing signaling to hepcidin via the BMP/SMAD pathway are associated with human disorders of iron metabolism, such as hereditary hemochromatosis and iron-refractory iron-deficiency anemia. Evidence suggests that signals in addition to iron stores influence hepcidin expression via the BMP/SMAD pathway. This review summarizes the details of BMP/SMAD signaling, with a particular focus on its role in iron homeostasis and iron-related diseases.
Overexpression of VEGF-C Causes Transient Lymphatic Hyperplasia but Not Increased Lymphangiogenesis in Regenerating Skin
Authors: Jeremy Goldman, Thomas X. Le, Mihaela Skobe, Melody A. Swartz
Journal: Circulation Research (2005)

Vascular endothelial growth factor (VEGF)-C is necessary for lymphangiogenesis and holds potential for lymphangiogenic therapy in diseases lacking adequate lymphatic drainage. However, the ability of VEGF-C to enhance sustainable, functional lymphatic growth in adult tissues remains unclear. To address this, we evaluated VEGF-C overexpression in adult lymphangiogenesis in regenerating skin. We used a model of mouse tail skin regeneration incorporating a suspension of either VEGF-C overexpressing tumor cells, which provide a continuous supplement of excess VEGF-C to the natural regenerating environment for more than 25 days, or otherwise identical control-transfected tumor cells. We found that excess VEGF-C did not enhance the rate of lymphatic endothelial cell (LEC) migration, the density of lymphatic vessels, or the rate of functionality - even though lymphatic hyperplasia was present early on. Furthermore, the hyperplasia disappeared when VEGF-C levels diminished, which occurred after 25 days, rendering the lymphatics indistinguishable from those in control groups. In vitro, we showed that whereas cell-derived VEGF-C could induce chemoattraction of LECs across a membrane (which involves amoeboid-like transmigration), it did not increase LEC chemoinvasion within a 3-dimensional fibrin matrix (which requires proteolytic migration). These results suggest that whereas excess VEGF-C may enhance early LEC proliferation and cause lymphatic vessel hyperplasia, it does not augment the physiological rate of migration or functionality, and by itself cannot sustain any lasting effects on lymphatic size, density, or organization in regenerating adult skin.
Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials
Authors: Ewan C. Goligher, Brian P. Kavanagh, Gordon D. Rubenfeld, Niall D. Ferguson
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Most randomized trials in critical care report no mortality benefit; this may reflect competing pathogenic mechanisms, patient heterogeneity, or true ineffectiveness of interventions. We hypothesize that in acute respiratory distress syndrome (ARDS), randomizing only those patients who show a favorable physiological response to an intervention would help ensure that only those likely to benefit would be entered into the study. If true, this would decrease study "noise" and reduce required sample size, thereby increasing the chances of finding true-positive outcomes. It would also lessen the chances of exposing patients to treatments that are unlikely to help or that could cause harm. We present a reanalysis of randomized clinical trials of positive end-expiratory pressure in ARDS that support this hypothesis.
Progress toward a National Blood System
Authors: D. MacN. Surgenor
Journal: New England Journal of Medicine (1976)

The success of the American Blood Commission in improving the effectiveness and efficiency of blood service delivery in the United States depends on the Commission's interactions with its members, with HEW and with the Congress. Active involvement of over 36 national organizations as dues-paying members representing both consumer/donors and providers gives the Commission considerable influence. HEW underwrites specific programs of the Commission and HEW agencies display co-operation and re-enforcement of its moves. The Congress has refrained from actions that might undercut the effort. An all-voluntary blood-donor system is a key American Blood Commission objective. The argument for voluntarism is supported by the need to control hepatitis, but other means of controlling hepatitis may be developed. The Commission's plan for a national blood system is based on securing voluntary compliance with guidelines recommended by peer groups within the Commission, and should facilitate a more effective national blood-transfusion system.
T cell receptor (TCR) recognition of MHC class I variants: intermolecular second-site reversion provides evidence for peptide/MHC conformational variation.
Authors: R Dyall, D H Fremont, S C Jameson, J Nikolić-Zugić
Journal: The Journal of Experimental Medicine (1996)

We investigated mechanistic differences in antigen presentation between murine MHC class I variants H-2K(b) and H-2K(bm)8. H-2K(bm)8 differs from H-2K(b) by four residues at the floor of the peptide-binding site, affecting its B pocket which interacts with the second (P2) residue of the peptide. The rest of the molecule, including the T cell receptor (TCR)-contacting residues, is identical to H-2K(b). Due to this variation, CTLs that recognize the ovalbumin 257-264 and HSV gB 498-505 peptides on H-2K(b) cannot recognize them on H-2K(bm)8. This could be due to impaired peptide binding or an altered peptide: K(bm)8 conformation. Peptide binding studies ruled out the first explanation. Molecular modeling indicated that the most obvious consequence of amino acid variation between peptide/H-2K(b) and peptide/H-2K(bm)8 complexes would be a loss of the conserved hydrogen bond network in the B pocket of the latter. This could cause conformational variation of bound peptides. Intermolecular second-site reversion was used to test this hypothesis: P2-substituted OVA and HSV peptides, engineered to restore the hydrogen bond network of the B pocket, were the only ones which restored CTL recognition. These results provide a molecular understanding of peptide/MHC conformational variation.
Type I Interferon Production Enhances Susceptibility to <i>Listeria monocytogenes</i> Infection
Authors: Ryan M. O'Connell, Supriya K. Saha, Sagar A. Vaidya, Kevin W. Bruhn, Gustavo A. Miranda, Brian Zarnegar, Andrea K. Perry, Bidong O. Nguyen, Timothy F. Lane, Tadatsugu Taniguchi, Jeff F. Miller, Genhong Cheng
Journal: The Journal of Experimental Medicine (2004)

Numerous bacterial products such as lipopolysaccharide potently induce type I interferons (IFNs); however, the contribution of this innate response to host defense against bacterial infection remains unclear. Although mice deficient in either IFN regulatory factor (IRF)3 or the type I IFN receptor (IFNAR)1 are highly susceptible to viral infection, we show that these mice exhibit a profound resistance to infection caused by the Gram-positive intracellular bacterium Listeria monocytogenes compared with wild-type controls. Furthermore, this enhanced bacterial clearance is accompanied by a block in L. monocytogenes–induced splenic apoptosis in IRF3- and IFNAR1-deficient mice. Thus, our results highlight the disparate roles of type I IFNs during bacterial versus viral infections and stress the importance of proper IFN modulation in host defense.
Precocious imbalance of autonomic nervous system in children with obstructive sleep apnea syndrome
Authors: Ottavio Vitelli, Giorgio Baccari, Jole Rabasco, Nicoletta Pietropaoli, Marco Del Pozzo, Maria Elena Liverani, Maria Pia Villa
Journal: European Respiratory Journal (2014)

The aim of this prospective study was to investigate the activity of the autonomic nervous system (ANS) during sleep in children with obstructive sleep apnea (OSA), in order to detect a precocious imbalance of ANS.   Materials and methods:  A total of 43 subjects between 4 to 15 years of age (7.26 ± 2.8 years), undergoing a diagnostic assessment for OSA in our Paediatric Sleep Centre (Rome, Italy), for habitual snoring and apnea were enrolled.A time domain index (the R-apnea index) was developed to evaluate heart rate variability (HRV) strictly related to obstructive events during sleep. Moreover Poincare plot of RR intervals during the whole night was calculated.   Results:  The R-apnea index was negatively correlated with apnea hypopnea index (AHI) (r = -0.360, p = 0.028). Furthermore AHI and the duration of the disease have been identified as the only variables that were significantly correlated with the R-apnea index.  Three groups were subsequently created on the basis of polysomnographic findings according to AHI. The R-apnea index resulted significantly lower in patient with severe OSA compared to primary snoring/mild OSA subjects (p  Looking at Poincare plot, SD1 (short term variability) showed a diminishing trend with severity of OSA, although not reaching statistical significance.   Conclusions:  Our findings suggest that an early autonomic impairment was present in children with OSA since HRV was altered in the very short term (R-apnea index) and in short term (SD1).