tbuckley/cabot-search huggingface dataset:
Clustered metabolic risk and leisure-time physical activity in adolescents: effect of dose?
Authors: Katja Pahkala, Olli J Heinonen, Hanna Lagström, Paula Hakala, Maarit Hakanen, Miika Hernelahti, Soile Ruottinen, Lauri Sillanmäki, Tapani Rönnemaa, Jorma Viikari, Olli T Raitakari, Olli Simell
Journal: British Journal of Sports Medicine (2010)

Objectives The authors studied the association of leisure-time physical activity (LTPA) with clustered and individual metabolic risk factors in adolescents taking into account diet and pubertal status. The authors also studied whether screen time was associated with clustered risk. Methods Self-reported LTPA and screen time, lipids, lipoproteins, apolipoproteins, high-sensitivity C reactive protein, blood pressure, body mass index (BMI), pubertal status and diet were assessed in 13-year-old adolescents (n=542) participating in an atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Activity groups were formed according to sex-specific LTPA index tertile cut-off points. BMI, high-density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure comprised the cluster. Results An increase in LTPA was associated with a decreased risk for clustered metabolic risk in girls. When sedentary and highly active adolescents were compared, an increase in LTPA decreased clustering of risk factors in boys as well. Little extra benefit on clustered risk was obtained by increasing LTPA from 30 MET h/week (eg, 4–5 h/week bicycling or playing soccer) to 50 MET h/week (eg, 7–8 h/week bicycling or playing soccer). LTPA was beneficially associated with BMI, HDL-C, systolic blood pressure and HDL-C/total cholesterol in girls and HDL-C in boys. Diet and pubertal status were similar in all activity groups. In girls, screen time &gt;2 h/day was associated with an increased risk for clustered risk, independent of LTPA. Conclusion Sedentary adolescents had an increased risk for clustered metabolic risk compared with physically more active peers. Only minor extra benefit was obtained when LTPA increased over 30 MET h/week. Focus in the prevention of clustered risk should especially be on avoiding sedentary lifestyle.
Perturbation of gene expression of the chromatin remodeling pathway in premature newborns at risk for bronchopulmonary dysplasia
Authors: Jennifer Cohen, Linda J Van Marter, Yao Sun, Elizabeth Allred, Alan Leviton, Isaac S Kohane
Journal: Genome biology (2007)

Abstract Background One-third to one-half of all infants born before the 28th week of gestation develop bronchopulmonary dysplasia (BPD). Inflammatory regulators appear to be involved in the pathogenesis of BPD, possibly beginning in fetal life. To evaluate the feasibility of using expression profiling in umbilical cord tissue to discover molecular signatures for developmental staging and for determining risk of BPD, we conducted a cross-sectional study of infants born at less than 28 weeks of gestation ( n = 54). Sections of umbilical cord were obtained at birth from 20 infants who later developed BPD and from 34 of their peers who did not develop BPD. Results Umbilical cord expression profiles at birth exhibited systematic differences in bioenergetic pathways with respect to gestational age. Infants who subsequently developed BPD had distinct signatures involving chromatin remodeling and histone acetylation pathways, which have previously been implicated in several adult onset lung diseases. These findings are consistent with prior work on inflammatory processes and bioenergetics in prematurity. Conclusion This study of gene expression of the newborn umbilical cord implicates the chromatin remodeling pathways in those premature infants who subsequently develop BPD. Larger sample sizes will be required to generate prognostic markers from umbilical cord profiles.
Reduction in Renal Vascular Responses to Angiotensin and Norepinephrine during Carotid Sinus Stimulation
Authors: RONALD G. GELLER, J. E. KENDRICK, G. L. Matson
Journal: Circulation Research (1967)

In dogs anesthetized with morphine and chloralose, the renal vascular responses to angiotensin and norepinephrine were studied under conditions of altered sympathetic nervous activity. The kidneys and one or both carotid sinuses were perfused at a constant rate of flow. Sympathetic activity was altered by changing the mean carotid sinus perfusion pressure from approximately 30 to 200 mm Hg. During maximal carotid sinus pressure, the renal vasoconstrictor responses to angiotensin and norepinephrine were reduced by an average of 52% and 47%, respectively. Similar results were obtained in innervated, chronically denervated, and excised kidneys perfused with the dogs' own blood. Increasing carotid sinus pressure alters the responsiveness of the renal vasculature to angiotensin and norepinephrine by some mechanism that is not dependent on the renal sympathetic nerves or on norepinephrine. It is proposed that raising mean carotid sinus pressure alters the concentration of some bloodborne substance and so reduces the vasoconstrictor responses to these vasoactive agents in the renal vascular bed.
Retinoic Acid Reduces Glomerular Injury in a Rat Model of Glomerular Damage
Authors: JU[Combining Diaeresis]RGEN WAGNER, CLAUDIUS DECHOW, CHRISTIAN MORATH, INGO LEHRKE, KERSTIN AMANN, RU[Combining Diaeresis]DIGER WALDHERR, JU[Combining Diaeresis]RGEN FLOEGE, EBERHARD RITZ
Journal: Journal of the American Society of Nephrology (2000)

Abstract. In the reaction of kidneys to injury, cytokine-driven proliferation plays an important role and precedes the development of glomerulosclerosis. There is great interest in agents that may interfere with such proliferation. Therefore, a rat model of mesangioproliferative glomerulonephritis (induced by anti-Thy1.1) was studied, and the effects of all- trans -retinoic acid (all- trans -RA) and isotretinoin, powerful antiproliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all- trans -RA or 40 mg/kg body wt isotretinoin ( n = 9 to 11 per group), using either a pretreatment (days -2 through 8) or posttreatment (days +3 through +8) protocol, i.e. , starting before or after the induction of anti-Thy1.1 nephritis, respectively. All- trans -RA prevented the BP increase evoked by anti-Thy1.1 (anti-Thy1.1/vehicle, 112.2 ± 4.8 mmHg; anti-Thy1.1/RA, 87.5 ± 2.5 mmHg; P &lt; 0.001). Treatment with all- trans -RA or isotretinoin produced a 70% decrease in the urinary albumin excretion rate ( P &lt; 0.02). Periodic acid-Schiff staining of saline-perfused kidneys (day 8) revealed significantly fewer glomerular cells in RA-treated nephritic rats (anti-Thy1.1/vehicle, 97 ± 3.1 cells/glomerulus; anti-Thy1.1/RA, 80 ± 4.4; P &lt; 0.02; control/vehicle, 69 ± 1.2). No difference was observed between all- trans -RA and isotretinoin treatment. The capillary occlusion scores were significantly lower for the anti-Thy1.1/RA-treated group (1.9 ± 0.1) than for the anti-Thy1.1/vehicle-treated group (2.9 ± 0.5, P &lt; 0.001). In the anti-Thy1.1/vehicle-treated group, 11.9 ± 1.1 glomerular cells were proliferating cell nuclear antigen-positive; however, in the anti-Thy1.1/RA-treated group, only 5.3 ± 0.8 cells were proliferating cell nuclear antigen-positive ( P &lt; 0.002; control, 2.2 ± 0.2). Glomerular mitoses were reduced by 67% in the anti-Thy1.1/RA-treated group, compared with the anti-Thy1.1/control group ( P &lt; 0.002). Glomerular staining for platelet-derived growth factor B-chain was significantly reduced in anti-Thy1.1-treated nephritic rats in the presence of isotretinoin or all- trans -RA, compared with the vehicle-treated group ( P &lt; 0.001). It is concluded that all- trans -RA limits glomerular proliferation, glomerular lesions, and albuminuria in an established model of renal damage. The findings point to retinoids as potential novel modulators of glomerular injury.
Salvage Chemotherapy for Pretreated Gastric Cancer: A Randomized Phase III Trial Comparing Chemotherapy Plus Best Supportive Care With Best Supportive Care Alone
Authors: Jung Hun Kang, Soon Il Lee, Do Hyoung Lim, Keon-Woo Park, Sung Yong Oh, Hyuk-Chan Kwon, In Gyu Hwang, Sang-Cheol Lee, Eunmi Nam, Dong Bok Shin, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Se Hoon Park
Journal: Journal of Clinical Oncology (2012)

When designing this trial, there was no evidence that salvage chemotherapy (SLC) in advanced gastric cancer (AGC) resulted in substantial prolongation of survival when compared with best supportive care (BSC). However, SLC is often offered to pretreated patients with AGC for anecdotal reasons.Patients with AGC with one or two prior chemotherapy regimens involving both fluoropyrimidines and platinum and with an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned in a ratio of 2:1 to SLC plus BSC or BSC alone. Choice of SLC-either docetaxel 60 mg/m(2) every 3 weeks or irinotecan 150 mg/m(2) every 2 weeks-was left to the discretion of investigators. Primary end point was overall survival (OS).Median OS was 5.3 months among 133 patients in the SLC arm and 3.8 months among 69 patients in the BSC arm (hazard ratio, 0.657; 95% CI, 0.485 to 0.891; one-sided P = .007). OS benefit for SLC was consistent in most of the prospectively defined subgroups, including age, PS, number of prior treatments, metastatic sites, hemoglobin levels, and response to prior chemotherapy. SLC was generally well tolerated, and adverse events were similar in the SLC and BSC arms. We found no median OS difference between docetaxel and irinotecan (5.2 v 6.5 months; P = .116).To our knowledge, this is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.
Regeneration and Tolerance Factor: A Novel Mediator of Glioblastoma-Associated Immunosuppression
Authors: Patrick Roth, Steffen Aulwurm, Isabella Gekel, Dagmar Beier, Roxanne G. Sperry, Michel Mittelbronn, Richard Meyermann, Kenneth D. Beaman, Michael Weller, Jörg Wischhusen
Journal: Cancer Research (2006)

Abstract Regeneration and tolerance factor (RTF) was originally identified in placenta where it is thought to be essential for fetal allograft survival. Here we report that RTF mRNA and protein are also expressed in human glioma cells in vitro and in vivo. Suppression of RTF expression by RNA interference promotes the lysis of glioma cells by natural killer (NK) and T cells in vitro. Moreover, RTF-depleted glioma cells are less tumorigenic than control cells in nude mice in vivo. Depletion of NK cells in these animals abolished this effect. RTF is thus a novel aberrantly expressed molecule which confers immune privilege to human malignant gliomas. (Cancer Res 2006; 66(7): 3852-8)
Histone H2AX Is a Mediator of Gastrointestinal Stromal Tumor Cell Apoptosis following Treatment with Imatinib Mesylate
Authors: Ying Liu, Michelle Tseng, Sophie A. Perdreau, Ferdinand Rossi, Cristina Antonescu, Peter Besmer, Jonathan A. Fletcher, Stefan Duensing, Anette Duensing
Journal: Cancer Research (2007)

Abstract Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and are caused by activating mutations of the KIT or platelet-derived growth factor receptor α (PDGFRA) tyrosine kinases. GISTs can be successfully treated with imatinib mesylate, a selective small-molecule protein kinase inhibitor that was first clinically approved to target the oncogenic BCR-ABL fusion protein kinase in chronic myelogenous leukemia, but which also potently inhibits KIT and PDGFR family members. The mechanistic events by which KIT/PDGFRA kinase inhibition leads to clinical responses in GIST patients are not known in detail. We report here that imatinib triggers GIST cell apoptosis in part through the up-regulation of soluble histone H2AX, a core histone H2A variant. We found that untreated GIST cells down-regulate H2AX in a pathway that involves KIT, phosphoinositide-3-kinase, and the ubiquitin/proteasome machinery, and that the imatinib-mediated H2AX up-regulation correlates with imatinib sensitivity. Depletion of H2AX attenuated the apoptotic response of GIST cells to imatinib. Soluble H2AX was found to sensitize GIST cells to apoptosis by aberrant chromatin aggregation and a transcriptional block. Our results underscore the importance of H2AX as a human tumor suppressor protein, provide mechanistic insights into imatinib-induced tumor cell apoptosis and establish H2AX as a novel target in cancer therapy. [Cancer Res 2007;67(6):2685–92]
Decision-Related Activity in Sensory Neurons: Correlations Among Neurons and with Behavior
Authors: Hendrikje Nienborg, Marlene R. Cohen, Bruce G. Cumming
Journal: Annual Review of Neuroscience (2012)

Neurons in early sensory cortex show weak but systematic correlations with perceptual decisions when trained animals perform at psychophysical threshold. These correlations are observed across repeated presentations of identical stimuli and cannot be explained by variation in external factors. The relationship between the activity of individual sensory neurons and the animal's behavioral choice means that even neurons in early sensory cortex carry information about an upcoming decision. This relationship, termed choice probability, may reflect the effect of fluctuations in neuronal firing rate on the animal's decision, but it can also reflect modulation of sensory responses by cognitive factors, or network properties such as variability that is shared among populations of neurons. Here, we review recent work clarifying the relationship among fluctuations in the responses of individual neurons, correlated variability, and behavior in a variety of tasks and cortical areas. We also discuss the possibility that choice probability may in part reflect the influence of cognitive factors on sensory neurons and explore the situations in which choice probability can be used to make inferences about the role of particular sensory neurons in the decision-making process.
Potential for Increased Human Foodborne Exposure to PCDD/F When Recycling Sewage Sludge on Agricultural Land
Authors: Karen Rideout, Kay Teschke
Journal: Environmental Health Perspectives (2004)

Sewage sludge from municipal wastewater treatment is used in agriculture as a nutrient source and to aid in moisture retention. To examine the potential impact of sludge-amended soil on exposures to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from plant and animal foods, we conducted a review of published empirical data from international sources. Levels of PCDD/F in municipal sewage sludge ranged from 0.0005 to 8,300 pg toxic equivalents (TEQ)/g. Background levels in soil ranged from 0.003 to 186 pg TEQ/g. In sludge-amended soils, levels of PCDD/F ranged from 1.4 to 15 pg TEQ/g. Studies that measured levels before and after sludge treatment showed an increase in soil concentration after treatment. Relationships between PCDD/F levels in soil and resulting concentrations in plants were very weakly positive for unpeeled root crops, leafy vegetables, tree fruits, hay, and herbs. Somewhat stronger relationships were observed for plants of the cucumber family. In all cases, large increases in soil concentration were required to achieve a measurable increase in plant contamination. A considerably stronger positive relationship was observed between PCDD/F in feed and resulting levels in cattle tissue, suggesting bioaccumulation. Although PCDD/Fs are excreted in milk, no association was found between feed contamination and levels of PCDD/Fs measured in milk. There is a paucity of realistic data describing the potential for entry of PCDD/Fs into the food supply via sewage sludge. Currently available data suggest that sewage sludge application to land used for most crops would not increase human exposure. However, the use of sludge on land used to graze animals appears likely to result in increased human exposure to PCDD/F.
Molecular Pathways: PI3K Pathway Targets in Triple-Negative Breast Cancers
Authors: Vallerie Gordon, Shantanu Banerji
Journal: Clinical Cancer Research (2013)

The triple-negative breast cancer (TNBC) subtype, defined clinically by the lack of estrogen, progesterone, and Her2 receptor expression, accounts for 10% to 15% of annual breast cancer diagnoses. Currently, limited therapeutic options have shown clinical benefit beyond cytotoxic chemotherapy. Defining this clinical cohort and identifying subtype-specific molecular targets remain critical for new therapeutic development. The current era of high-throughput molecular analysis has revealed new insights into these targets and confirmed the phosphoinositide 3-kinase (PI3K) as a key player in pathogenesis. The improved knowledge of the molecular basis of TNBC in parallel with efforts to develop new PI3K pathway-specific inhibitors may finally produce the therapeutic breakthrough that is desperately needed.
Treatment of paediatric malaria during a period of drug transition to artemether-lumefantrine in Zambia: cross sectional study
Authors: Dejan Zurovac, Mickey Ndhlovu, Alexander K Rowe, Davidson H Hamer, Donald M Thea, Robert W Snow
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To evaluate treatment practices for uncomplicated malaria after the policy change from chloroquine to sulfadoxine-pyrimethamine and to artemether-lumefantrine in Zambia. <b>Design</b> Cross sectional survey. <b>Setting</b> Outpatient departments of all government and mission facilities in four districts in Zambia. <b>Participants</b> 944 children with uncomplicated malaria seen by 103 health workers at 94 health facilities. <b>Main outcome measures</b> Antimalarial prescriptions in accordance with national guidelines and influence of factors on health workers9 decision to prescribeartemether-lumefantrine. <b>Results</b> Artemether-lumefantrine, sulfadoxine-pyrimethamine, and chloroquine were available, respectively, at 48 (51%), 94 (100%), and 71 (76%) of the 94 facilities. Of 944 children with uncomplicated malaria, only one child (0.1%) received chloroquine. Among children weighing less than 10 kg, sulfadoxine-pyrimethamine was commonly prescribed in accordance with guidelines (439/550, 79.8%). Among the children weighing 10 kg or more, sulfadoxine-pyrimethamine was commonly prescribed (266/394, 68%), whereas recommended artemether-lumefantrine was prescribed for only 42/394 (11%) children. Among children weighing 10 kg or more seen at facilities where artemether-lumefantrine was available, the same pattern was observed: artemether-lumefantrine was prescribed for only 42/192 (22%) children and sulfadoxine-pyrimethamine remained the drug of choice (103/192, 54%). Programmatic activities such as in-service training and provision of job aids did not seem to influence the prescribing of artemether with lumefantrine. <b>Conclusion</b> Although the use of chloroquine for uncomplicated malaria was succesfully discontinued in Zambia, the change of drug policy towards artemether-lumefantrine does not necessarily translate into adequate use of this drug at the point of care.
Ultrasound Processing and Computing: Review and Future Directions
Authors: George York, Yongmin Kim
Journal: Annual Review of Biomedical Engineering (1999)

Since the introduction of medical ultrasound in the 1950s, modern diagnostic ultrasound has progressed to see many major diagnostic tools come into widespread clinical use, such as B-mode imaging, color-flow imaging, and spectral Doppler. New applications, such as panoramic imaging, three-dimensional imaging, and quantitative imaging, are now beginning to be offered on some commercial ultrasound machines and are expected to grow in popularity. In this review, we focus on the various algorithms, their processing requirements, and the challenges of these ultrasound modes. Whereas the older, mature B and color-flow modes could be systolically implemented using hardwired components and boards, new applications, such as three-dimensional imaging and image feature extraction, are being implemented more by using programmable processors. This trend toward programmable ultrasound machines will continue, because the programmable approach offers the advantages of quick implementation of new applications without any additional hardware and the flexibility to adapt to the changing requirements of these dynamic new applications.
Dissociation of membrane binding and lytic activities of the lymphocyte pore-forming protein (perforin).
Authors: J D Young, A Damiano, M A DiNome, L G Leong, Z A Cohn
Journal: The Journal of Experimental Medicine (1987)

Granules isolated from CTL and NK cells contain a cytolytic pore-forming protein (PFP/perforin). At low temperatures (on ice), PFP binds to erythrocyte membranes without producing hemolysis. Hemolysis occurs when the PFP-bound erythrocytes are warmed up to 37 degrees C, which defines a temperature-dependent, lytic (pore-formation) step distinct from the membrane-binding event. Ca2+ and neutral pH are required for both membrane binding and pore formation by PFP. Serum, LDL, HDL, and heparin inhibit the hemolytic activity of PFP by blocking its binding to lipid membranes. Lysis by PFP that has bound to erythrocyte membranes is no longer susceptible to the effect of these inhibitors. The hemolytic activities associated with intact granules and solubilized PFP show different requirements for Ca2+ and pH, indicating that cytolysis produced by isolated granules may involve an additional step, possibly fusion of granules with membranes. It is suggested that three distinct Ca2+- and pH-dependent events may be involved during cell killing by CTL and NK cells: fusion of cytoplasmic granules of effector cells with their plasma membrane, releasing PFP from cells; binding of the released PFP to target membranes; and insertion of monomers and the subsequent formation of lytic pores in the target membrane. The serum-mediated inhibition of membrane binding by PFP could prevent the accidental injury of bystander cells by cell-released PFP, but would allow cytolysis to proceed to completion once PFP has bound to the target membrane.
Quetelet's Index and Risk of Colon Cancer in College Alumni
Authors: I-M. Lee, R. S. Paffenbarger
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Quetelet's Index and Risk of Colon Cancer in College Alumni Get access I-Min Lee, I-Min Lee * Department of Epidemiology, Harvard University School of Public HealthBoston, Mass *Correspondence to : I-Min Lee, M.B., B.S., SC.D., Department of Epidemoilogy, Harvard University school of Public Health, 677 Huntington Ave., Boston, MA 02115 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ralph S. Paffenbarger, Jr. Ralph S. Paffenbarger, Jr. Department of Epidemiology, Harvard University School of Public Health, and Division of Epidemiology, Stanford University School of MedicineStanford, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 17, 2 September 1992, Pages 1326–1331, https://doi.org/10.1093/jnci/84.17.1326 Published: 02 September 1992 Article history Received: 13 March 1992 Revision received: 22 May 1992 Accepted: 29 May 1992 Published: 02 September 1992
Pulmonary hamartoma mimicking primary bronchoalveolar cell carcinoma
Authors: Chun-Chao Huang, Chin-Yin Sheu, Chi-Yuan Tzen, Wen-Chien Huang
Journal: Thorax (2011)

A 52-year-old man with transitional cell carcinoma underwent a chest CT because of a newly developed pulmonary nodule observed on a chest radiograph. In addition to the nodule, a 2.8×2.4 cm well-circumscribed, pure ground-glass opacity with air cyst formation was incidentally found (figure 1). There was no …