tbuckley/cabot-search huggingface dataset:
Soybean protein diet increases low density lipoprotein receptor activity in mononuclear cells from hypercholesterolemic patients.
Authors: M R Lovati, C Manzoni, A Canavesi, M Sirtori, V Vaccarino, M Marchi, G Gaddi, C R Sirtori
Journal: Journal of Clinical Investigation (1987)

The effect of two diets containing different protein sources (animal vs. soybean) on the low density lipoprotein (LDL) receptor activity was tested in freshly isolated mononuclear cells from 12 individuals with severe type II hyperlipoproteinemia. The two diets, both taken for 4 wk in a crossover design were of otherwise identical composition. During the soybean protein diet period, total cholesterol was reduced by 15.9% and LDL-cholesterol by 16.4%. The diet containing animal proteins exerted no significant change in plasma lipid levels vs. the baseline findings. The soybean diet regimen dramatically affected the degradation of LDL by mononuclear cells. Degradation was increased 16-fold vs. the basal activity and 8-fold compared with the standard low lipid diet with animal proteins. There was, however, no clear relationship between the reduction of total and LDL-cholesterolemia and the increased LDL degradation. These findings confirm similar data previously obtained in cholesterol-fed rats and suggest that some factor/s, most likely of a protein nature, may regulate the expression of lipoprotein receptors in peripheral cells, particularly when receptor activity is suppressed by experimental diets and/or spontaneous hypercholesterolemia.
GDF11 Does Not Rescue Aging-Related Pathological Hypertrophy
Authors: Shavonn C. Smith, Xiaoxiao Zhang, Xiaoying Zhang, Polina Gross, Timothy Starosta, Sadia Mohsin, Michael Franti, Priyanka Gupta, David Hayes, Maria Myzithras, Julius Kahn, James Tanner, Steven M. Weldon, Ashraf Khalil, Xinji Guo, Abdelkarim Sabri, Xiongwen Chen, Scott MacDonnell, Steven R. Houser
Journal: Circulation Research (2015)

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family of secreted factors. A recent study showed that reduced GDF11 blood levels with aging was associated with pathological cardiac hypertrophy (PCH) and restoring GDF11 to normal levels in old mice rescued PCH.To determine whether and by what mechanism GDF11 rescues aging dependent PCH.Twenty-four-month-old C57BL/6 mice were given a daily injection of either recombinant (r) GDF11 at 0.1 mg/kg or vehicle for 28 days. rGDF11 bioactivity was confirmed in vitro. After treatment, rGDF11 levels were significantly increased, but there was no significant effect on either heart weight or body weight. Heart weight/body weight ratios of old mice were not different from 8- or 12-week-old animals, and the PCH marker atrial natriuretic peptide was not different in young versus old mice. Ejection fraction, internal ventricular dimension, and septal wall thickness were not significantly different between rGDF11 and vehicle-treated animals at baseline and remained unchanged at 1, 2, and 4 weeks of treatment. There was no difference in myocyte cross-sectional area rGDF11 versus vehicle-treated old animals. In vitro studies using phenylephrine-treated neonatal rat ventricular myocytes, to explore the putative antihypertrophic effects of GDF11, showed that GDF11 did not reduce neonatal rat ventricular myocytes hypertrophy, but instead induced hypertrophy.Our studies show that there is no age-related PCH in disease-free 24-month-old C57BL/6 mice and that restoring GDF11 in old mice has no effect on cardiac structure or function.
Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: Correlation with markers of disease activity
Authors: M.G. Alexandrakis, F.H. Passam, A. Sfiridaki, E. Kandidaki, P. Roussou, D.S. Kyriakou
Journal: American Journal of Hematology (2003)

Abstract Hepatocyte growth factor (HGF) has been shown to be involved in angiogenesis, epithelial cell proliferation, and osteoclast activation. HGF and its receptor are expressed on myeloma cell lines and could be involved in the pathogenesis of bone destruction in multiple myeloma (MM). The aim of this study was to examine serum levels of HGF in untreated MM patients and its correlation with bone turnover indices and markers of disease activity. Forty‐seven newly diagnosed MM patients and 25 controls were included: 12 patients were of stage I, 13 of stage II, and 22 of stage III (Durie–Salmon classification). Bone lesions were scored from 0 to 3, according to X‐ray findings. Serum osteocalcin (OC), interleukin‐6 (IL‐6), TNF‐α, β 2 ‐microglobulin (β 2 M), CRP, calcium, and 24‐hr urine N‐telopeptide cross‐links of collagen breakdown (NTx) were determined. HGF levels were significantly higher at stage III compared to stages II and I (medians: 1,990.4 vs. 1,743.8 and 1,432.4 pg/mL, respectively, P &lt; 0.05). Similarly, NTx, IL‐6, TNF‐α, CRP, β 2 M, and calcium increased significantly with advancing stage ( P &lt; 0.01). OC was higher at stage I in comparison to stages II and III ( P &lt; 0.01). All parameters were significantly higher in patients than controls. HGF showed a strong correlation with IL‐6 and TNF‐α and less with β 2 M, CRP, NTx, and OC. We conclude that serum HGF levels are increased in advanced stages of MM disease and extended bone lesions. HGF correlates with IL‐6 and TNF‐α, which are cytokines involved in osteoclast stimulation in MM. However, an independent association of HGF with bone turnover markers was not shown in this study, thus its role in MM bone disease needs to be further clarified. Am. J. Hematol. 72:229–233, 2003. © 2003 Wiley‐Liss, Inc.
Morbidity and mortality in children with obstructive sleep apnoea: a controlled national study
Authors: Poul Jennum, Rikke Ibsen, Jakob Kjellberg
Journal: Thorax (2013)

<h3>Background</h3> Little is known about the diagnostic patterns of obstructive sleep apnoea (OSA) in children. A study was undertaken to evaluate morbidity and mortality in childhood OSA. <h3>Methods</h3> 2998 patients aged 0–19 years with a diagnosis of OSA were identified from the Danish National Patient Registry. For each patient we randomly selected four citizens matched for age, sex and socioeconomic status, thus providing 11 974 controls. <h3>Results</h3> Patients with OSA had greater morbidity at least 3 years before their diagnosis. The most common contacts with the health system arose from infections (OR 1.19, 95% CI 1.01 to 1.40); endocrine, nutritional and metabolic diseases (OR 1.30, 95% CI 0.94 to 1.80); nervous conditions (OR 2.12, 95% CI 1.65 to 2.73); eye conditions (OR 1.43, 95% CI 1.07 to 1.90); ear, nose and throat (ENT) diseases (OR 1.61, 95% CI 1.33 to 1.94); respiratory system diseases (OR 1.78, 95% CI 1.60 to 1.98); gastrointestinal diseases (OR 1.34, 95% CI 1.09 to 1.66); skin conditions (OR 1.32, 95% CI 1.02 to 1.71); congenital malformations (OR 1.56, 95% CI 1.31 to 1.85); abnormal clinical or laboratory findings (OR 1.21, 95% CI 1.06 to 1.39); and other factors influencing health status (OR 1.29, 95% CI 1.16 to 1.43). After diagnosis, OSA was associated with incidences of endocrine, nutritional and metabolic diseases (OR 1.78, 95% CI 1.29 to 2.45), nervous conditions (OR 3.16, 95% CI 2.58 to 3.89), ENT diseases (OR 1.45, 95% CI 1.14 to 1.84), respiratory system diseases (OR 1.94, 95% CI 1.70 to 2.22), skin conditions (OR 1.42, 95% CI 1.06 to 1.89), musculoskeletal diseases (OR 1.29, 95% CI 1.01 to 1.64), congenital malformations (OR 1.83, 95% CI 1.51 to 2.22), abnormal clinical or laboratory findings (OR 1.16, 95% CI 1.06 to 1.27) and other factors influencing health status (OR 1.35, 95% CI 1.20 to 1.51). The 5-year death rate was 70 per 10 000 for patients and 11 per 10 000 for controls. The HR for cases compared with controls was 6.58 (95% CI 3.39 to 12.79; p&lt;0.001). <h3>Conclusions</h3> Children with OSA have significant morbidities several years before and after their diagnosis.
An HLA-DR–Degenerate Epitope Pool Detects Insulin-like Growth Factor Binding Protein 2–Specific Immunity in Patients with Cancer
Authors: Kimberly R. Kalli, Christopher J. Krco, Lynn C. Hartmann, Karin Goodman, Matthew J. Maurer, Chao Yu, Elliot M. Johnson, Courtney L. Erskine, Mary L. Disis, Peter J. Wettstein, John D. Fikes, Melanie Beebe, Glenn Ishioka, Keith L. Knutson
Journal: Cancer Research (2008)

Abstract Recent studies have shown the importance of helper CD4 T cells in initiating and sustaining tumor-specific CD8 T-cell immunity. This has paved the way for identifying MHC class II epitopes that could be incorporated into class I–based vaccines. In this study, the goal was to identify an HLA-DR–degenerate epitope pool derived from insulin-like growth factor binding protein 2 (IGFBP-2). IGFBP-2, a regulator of insulin-like growth factor action, is overexpressed in the majority of breast and ovarian cancers. Using algorithms, we predicted 29 HLA-DR1–binding epitopes. Binding assays targeting 15 different HLA-DRs revealed that 10 epitopes were degenerate, binding to at least four different HLA-DR variants. An IFN-γ enzyme-linked immunosorbent spot assay was used to assess immunity to these 10 epitopes in 48 patients with either breast or ovarian cancer and 18 controls. Elevated T-cell immunity in patients was detected in 4 of the 10 epitopes (IGFBP2.17, IGFBP2.22, IGFBP2.249, and IGFBP2.293). The cumulative T-cell frequency of these four epitopes was elevated in patients relative to controls. All four peptides are naturally processed and presented to CD4 T-cells. The degenerate pool of peptides covers nearly 80% of patients and may be useful for augmenting CD4 T-cell immunity in patients undergoing immunization. [Cancer Res 2008;68(12):4893–901]
Annexin A1 Counteracts Chemokine-Induced Arterial Myeloid Cell Recruitment
Authors: Maik Drechsler, Renske de Jong, Jan Rossaint, Joana R. Viola, Giovanna Leoni, Ji Ming Wang, Jochen Grommes, Rabea Hinkel, Christian Kupatt, Christian Weber, Yvonne Döring, Alexander Zarbock, Oliver Soehnlein
Journal: Circulation Research (2014)

Rationale: Chemokine-controlled arterial leukocyte recruitment is a crucial process in atherosclerosis. Formyl peptide receptor 2 (FPR2) is a chemoattractant receptor that recognizes proinflammatory and proresolving ligands. The contribution of FPR2 and its proresolving ligand annexin A1 to atherosclerotic lesion formation is largely undefined. Objective: Because of the ambivalence of FPR2 ligands, we here investigate the role of FPR2 and its resolving ligand annexin A1 in atherogenesis. Methods and Results: Deletion of FPR2 or its ligand annexin A1 enhances atherosclerotic lesion formation, arterial myeloid cell adhesion, and recruitment. Mechanistically, we identify annexin A1 as an endogenous inhibitor of integrin activation evoked by the chemokines CCL5, CCL2, and CXCL1. Specifically, the annexin A1 fragment Ac2-26 counteracts conformational activation and clustering of integrins on myeloid cells evoked by CCL5, CCL2, and CXCL1 through inhibiting activation of the small GTPase Rap1. In vivo administration of Ac2-26 largely diminishes arterial recruitment of myeloid cells in a FPR2-dependent fashion. This effect is also observed in the presence of selective antagonists to CCR5, CCR2, or CXCR2, whereas Ac2-26 was without effect when all 3 chemokine receptors were antagonized simultaneously. Finally, repeated treatment with Ac2-26 reduces atherosclerotic lesion sizes and lesional macrophage accumulation. Conclusions: Instructing the annexin A1-FPR2 axis harbors a novel approach to target arterial leukocyte recruitment. With the ability of Ac2-26 to counteract integrin activation exerted by various chemokines, delivery of Ac2-26 may be superior in inhibition of arterial leukocyte recruitment when compared with blocking individual chemokine receptors.
Use of Advanced Radiology During Visits to US Emergency Departments for Injury-Related Conditions, 1998-2007
Authors: Frederick Kofi Korley, Julius Cuong Pham, Thomas Dean Kirsch
Journal: JAMA (2010)

Excessive use of medical imaging increases health care costs and exposure to ionizing radiation (a potential carcinogen) without yielding significant benefits to all patients.To determine whether there has been a change in the prevalence of emergency department visits for injury-related conditions for which computed tomography (CT) or magnetic resonance imaging (MRI) was obtained and whether there has been a change in the diagnosis of life-threatening conditions and patient disposition.Retrospective cross-sectional analysis of emergency department visits using data from the National Hospital Ambulatory Medical Care Survey (1998-2007). Sampled visits were weighted to produce estimates for the United States.Proportion of visits for injury-related conditions during which a CT or MRI was obtained, a life-threatening condition was diagnosed (eg, cervical spine fracture, skull fracture, intracranial bleeding, liver and spleen laceration), and which resulted in hospital and intensive care unit admission.The prevalence of CT or MRI use during emergency department visits for injury-related conditions increased from 6% (95% confidence interval [CI], 5%-7%) (257 of 5237 visits) in 1998 to 15% (95% CI, 14%-17%) (981 of 6567 visits) in 2007 (P < .001 for trend). There was a small increase in the prevalence of life-threatening conditions (1.7% [95% CI, 1.2%-2.2%; 89 of 5237 visits] in 1998 and 2.0% [95% CI, 1.6%-2.5%; 142 of 6567 visits] in 2007; P=.04 for trend) [corrected].There was no change in prevalence of visits during which patients were either admitted to the hospital (5.9% [95% CI, 4.9%-6.9%] in 1998 and 5.5% [95% CI, 4.7%-6.5%] in 2007; P = .50 for trend) or to an intensive care unit (0.62% [95% CI, 0.40%-1.00%] in 1998 and 0.80% [95% CI, 0.53%-1.21%] in 2007; P = .14 for trend). Visits during which CT or MRI was obtained lasted 126 minutes (95% CI, 123-131 minutes) longer than those for which CT or MRI was not obtained.From 1998 to 2007, the prevalence of CT or MRI use during emergency department visits for injury-related conditions increased significantly, without an equal increase in the prevalence of life-threatening conditions.
Impending child abuse. Psychosomatic symptoms in adults as a clue
Authors: R. P. Mogielnicki
Journal: JAMA (1977)

Adult patients involved in or threatened by the possibility of committing child abuse may develop acute functional symptoms that result in their seeking emergency medical help. Three cases are presented as examples of this relationship. In two, the functional symptom was paralysis or paresis. In the third, symptoms were more diffuse. Recognition of the association between functional symptoms and child abuse may permit intervention before serious child injury occurs. (<i>JAMA</i>237:1109-1111, 1977)
C. elegans neuroscience: genetics to genome
Authors: Martin Chalfie, Erik M. Jorgensen
Journal: Trends in Genetics (1998)

From their earliest experiments, researchers using Caenorhabditis elegans have been interested in the role of genes in the development and function of the nervous system. As the C. elegans Genome Project completes the genomic sequence, we review the accomplishments of these researchers and the impact that the Genome Project has bad on their research. We also speculate on future directions in this research that are enabled by the efforts of the Genome Project.
Antiplatelet and Anticoagulation Therapy for Acute Coronary Syndromes
Authors: Deepak L. Bhatt, Jean-Sébastien Hulot, David J. Moliterno, Robert A. Harrington
Journal: Circulation Research (2014)

The past 2 decades have witnessed the introduction and demise of several different antithrombotic medications for acute coronary syndromes. Part of the assessment of these compounds has been their effect on thrombotic events relative to the degree of increase in bleeding events. This review will outline the data supporting various antiplatelet and anticoagulant therapies and their combinations in patients with acute coronary syndromes and related disorders in both the acute and chronic phases of therapy.
Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial.
Authors: G Riethmüller, E Holz, G Schlimok, W Schmiegel, R Raab, K Höffken, R Gruber, I Funke, H Pichlmaier, H Hirche, P Buggisch, J Witte, R Pichlmayr
Journal: Journal of Clinical Oncology (1998)

PURPOSE As previously shown, antibody treatment increased survival of patients with resected colorectal cancer of stage Dukes' C. Since the 5-year analysis was criticized because of the wide range (2.7 to 7.5 years) of follow-up time, we performed a 7-year analysis with only four of 189 patients monitored for less than 5 years. PATIENTS AND METHODS A total of 189 patients with resected Dukes' C colorectal cancer were randomly allocated to infusions of a total of 900 mg 17-1A antibody, 500 mg postoperatively followed by 4 monthly doses of 100 mg (n=99), or to observation only (n=90). Primary end points were overall survival and disease-free interval. Patients were stratified by a dynamic randomization according to center, sex, location of tumor, number of affected lymph nodes, and preoperative carcinoembryonic antigen concentration. RESULTS Randomization produced balanced distribution of risk factors. After 7 years of follow-up evaluation, treatment had reduced overall mortality by 32% (Cox's proportional hazard, P &lt; .01; log-rank, P=.01) and decreased the recurrence rate by 23% (Cox's proportional hazard, P &lt; .04; log-rank, P=.07). The intention-to-treat analysis gave a significant effect for overall survival (Cox's proportional hazard, P &lt; .01; log-rank, P=.02) and disease-free survival (Cox's proportional hazard, P=.02; log-rank, P=.11 ). While distant metastases were significantly reduced (Cox's proportional hazard, P=.004; log-rank, P=.004), local relapses were not (Cox's proportional hazard, P=.65; log-rank, P=.52). This differential effect of 17-1A antibody on disseminated isolated tumor cells versus occult local satellites may explain the increased significance seen in the overall survival. CONCLUSION The now-matured study shows that 17-1A antibody administered after surgery prevents the development of distant metastasis in approximately one third of patients. The therapeutic effect is maintained after 7 years of follow-up evaluation.
Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation
Authors: Maximilian Nitschké, David Aebischer, Michael Abadier, Simone Haener, Matije Lucic, Benjamin Vigl, Hervé Luche, Hans Jörg Fehling, Oliver Biehlmaier, Ruth Lyck, Cornelia Halin
Journal: Blood (2012)
Oncogenic H-Ras Up-regulates Expression of Ku80 to Protect Cells from γ-Ray Irradiation in NIH3T3 Cells
Authors: In-Youb Chang, Cha-Kyung Youn, Hong-Beum Kim, Mi-Hwa Kim, Hyun-Ju Cho, Young Yoon, Yun-Sil Lee, Myung-Hee Chung, Ho Jin You
Journal: Cancer Research (2005)

Abstract The Ras activation contributes to radioresistance, but the mechanism is unclear. This article shows that the expression of the dominant-positive H-Ras increased the Ku80 level, which is one of the key enzymes involved in repairing dsDNA breaks (DSB). After exposing the cells to ionizing radiation and analyzing them using an electrophoretic mobility shift assay and pulsed-field gel electrophoresis, it was found that activated H-Ras expression in NIH3T3 cells increases the DNA-binding activity of Ku80 and increases the DSB repair activity. Ku80 small interfering RNA expression was shown to reduce the oncogenic H-Ras-mediated increase in the DSBs and suppress the oncogenic H-Ras-mediated resistance of the cells to γ-ray irradiation, whereas Ku80 overexpression in the NIH3T3 cells significantly increased the radioresistance. These results suggest that the Ku80 expression induced by oncogenic H-Ras seems to play an important role in protecting cells against γ-ray irradiation.
Cancer after pre-eclampsia: follow up of the Jerusalem perinatal study cohort
Authors: Ora Paltiel, Yehiel Friedlander, Efrat Tiram, Micha Barchana, Xiaonan Xue, Susan Harlap
Journal: BMJ (2004)

<b>&gt;Objective</b> To compare the incidence of cancer among women with and without a history of pre-eclampsia. <b>Design</b> Cohort study. <b>Setting</b> Jerusalem perinatal study of women who delivered in three large hospitals in West Jerusalem during 1964-76. <b>Participants</b> 37 033 women. <b>Main outcome measures</b> Age adjusted and multivariable adjusted hazard ratios for cancer incidence for the entire cohort and for women who were primiparous at study entry. <b>Results</b> Cancer developed in 91 women who had pre-eclampsia and 2204 who did not (hazard ratio 1.27, 95% confidence interval 1.03 to 1.57). The risk of site specific cancers was increased, particularly of the stomach, ovary epithelium, breast, and lung or larynx. The incidence of cancer of the stomach, breast, ovary, kidney, and lung or larynx was increased in primiparous women at study entry who had a history pre-eclampsia. <b>Conclusions</b> A history of pre-eclampsia is associated with increases in overall risk of cancer and incidence at several sites. This may be explained by environmental and genetic factors common to the development of pre-eclampsia and cancer in this population.
Four Children Crushed in their Driveways
Authors: P Godbole, D C Crabbe, M D Stringer
Journal: Journal of the Royal Society of Medicine (2001)

Pedestrian injuries are a leading cause of mortality and morbidity in childhood1. In most cases the child is struck by a fast-moving vehicle, but injuries sustained in the driveway form a distinct subgroup2. We report four cases seen over a 5-year period (1995-1999) in a regional paediatric surgical centre.
What Price Pain Relief?
Authors: Judith S. Hochman, Nirav R. Shah
Journal: Circulation (2006)

hronic pain affects more than 50 million Americans and results in more than 25 million physician visits a year for lower back pain alone. 1The burden is particularly great in the elderly, in whom associated cardiovascular disease is the leading cause of death.Nonselective, nonaspirin, nonsteroidal antiinflammatory agents (NSAIDs) are effective analgesic, antiinflammatory, and antipyretic agents, but associated gastrointestinal toxicity led to the development and widespread use of selective cyclooxygenase (COX)-2 inhibitors.Originally introduced for use in chronic conditions such as osteoarthritis, they are today used to mitigate acute pain in numerous conditions.Their benefit was presumed to be from their selective inhibition of COX 2, which along with COX-1 is responsible for the conversion of arachidonic acid to prostaglandin H 2 .Adverse events associated with NSAIDs were attributed to their inhibition of COX 1, which downstream would normally result in the production of prostaglandins responsible for maintenance of gastrointestinal integrity. 2More recent investigations, however, have identified that both COX-1 and COX-2 are involved in vascular hemostasis, and selective COX-2 inhibitors can have net prothrombotic effects.COX-2 inhibitors lower levels of prostacyclin, a platelet inhibitor and vasodilator, whereas uninhibited COX-1 action results in continued thromboxane A 2 production, which promotes platelet aggregation. 3There is mounting evidence that nonselective NSAIDs, previously thought to be neutral or beneficial for risk of cardiovascular disease, may also confer harm because of each agent's relative COX-1/COX-2 prothrombotic effects and potential to reduce glomerular filtration, exacerbate congestive heart failure, and raise blood pressure.