tbuckley/cabot-search huggingface dataset:
Calculation of plasma concentrations of intra-arterially infused compounds in forearm plethysmography
Authors: Tobias A Bruning, Michiel J.B Kemme, Peter C Chang, Yvonne Muizert, Pieter A van Zwieten
Journal: Cardiovascular Research (1998)

Objective: Forearm blood flow plethysmography is a widely accepted in vivo technique for pharmacologic and functional studies in peripheral resistance vessels and veins. Pharmacological effects on forearm blood flow (FBF) are usually expressed by means of dose-response relationships. This approach does not consider the influence of variations in FBF on the actual plasma concentrations of compounds infused, and is less suitable for quantitative comparison of the pharmacologic characteristics of different compounds. The aim of this study was to validate an equation to estimate the plasma concentrations of intra-arterially infused compounds. This was done at different levels of FBF, using an indicator dilution technique with constant rate infusions of indocyanine green (ICG) and inulin. Methods: ICG (0.5 mg/min) and inulin (5 mg/min) were infused into the brachial artery in the presence of sodium nitroprusside (10 ng/kg/min; to obtain high FBF), vehicle (0.9% saline; for intermediate FBF), and methoxamine (1 μg/kg/min; for low FBF). FBF was measured using venous occlusion plethysmography in six healthy male volunteers. Plasma concentrations of the indicators, measured in venous blood samples, were compared with the calculated values. Results: Excellent correspondence was observed between calculated and measured plasma concentrations for both ICG and inulin. Venous plasma concentrations of ICG (≥95% protein binding) reached steady-state within four min independent of FBF. Alternatively, the time required for venous plasma concentrations of inulin (not bound to protein) to reach steady-state appeared dependent on FBF. Conclusion: Total plasma concentrations of intra-arterially infused drugs can be appropriately estimated at the level of the arterioles by the proposed equation.
Eradication of minimal residual disease in hairy cell leukemia
Authors: Farhad Ravandi, Jeffrey L. Jorgensen, Susan M. O'Brien, Srdan Verstovsek, Charles A. Koller, Stefan Faderl, Francis J. Giles, Alessandra Ferrajoli, William G. Wierda, Shirley Odinga, Xuelin Huang, Deborah A. Thomas, Emil J. Freireich, Dan Jones, Michael J. Keating, Hagop M. Kantarjian
Journal: Blood (2006)
Counterpulsation Effects of Coronary Blood Flow and Cardiac Oxygen Utilization
Authors: L. J. HIRSCH, S. LLUCH, L. N. KATZ, A. Ellis
Journal: Circulation Research (1966)

Counterpulsation in dogs with normal systemic arterial blood pressure produced a reduction in myocardial oxygen consumption without a significant concomitant change in total coronary flow. In dogs with a deteriorating heart and low systemic arterial blood pressure, myocardial oxygen consumption became dependent on coronary flow. Under these circumstances, counterpulsation produced an increase in coronary flow, and with it a secondary augmentation of cardiac oxygen consumption. Counterpulsation reduced the mean systemic arterial blood pressure during ventricular ejection to a greater degree when the control level of this pressure was normal than when it was hypotensive. This lessened effect may also occur when the heart has deteriorated. The mechanisms involved in causing the several effects of counterpulsation are discussed.
Identification of a Novel Recepteur d'Origine Nantais/c-Met Small-Molecule Kinase Inhibitor with Antitumor Activity <i>In vivo</i>
Authors: Yihong Zhang, Paula J. Kaplan-Lefko, Karen Rex, Yajing Yang, Jodi Moriguchi, Tao Osgood, Bethany Mattson, Angela Coxon, Monica Reese, Tae-Seong Kim, Jasmine Lin, April Chen, Teresa L. Burgess, Isabelle Dussault
Journal: Cancer Research (2008)

Abstract Recepteur d'origine nantais (RON) is a receptor tyrosine kinase closely related to c-Met. Both receptors are involved in cell proliferation, migration, and invasion, and there is evidence that both are deregulated in cancer. Receptor overexpression has been most frequently described, but other mechanisms can lead to the oncogenic activation of RON and c-Met. They include activating mutations or gene amplification for c-Met and constitutively active splicing variants for RON. We identified a novel inhibitor of RON and c-Met, compound I, and characterized its in vitro and in vivo activities. Compound I selectively and potently inhibited the kinase activity of RON and c-Met with IC50s of 9 and 4 nmol/L, respectively. Compound I inhibited hepatocyte growth factor–mediated and macrophage-stimulating protein–mediated signaling and cell migration in a dose-dependent manner. Compound I was tested in vivo in xenograft models that either were dependent on c-Met or expressed a constitutively active form of RON (RONΔ160 in HT-29). Compound I caused complete tumor growth inhibition in NIH3T3 TPR-Met and U-87 MG xenografts but showed only partial inhibition in HT-29 xenografts. The effect of compound I in HT-29 xenografts is consistent with the expression of the activating b-Raf V600E mutation, which activates the mitogen-activated protein kinase pathway downstream of RON. Importantly, tumor growth inhibition correlated with the inhibition of c-Met–dependent and RON-dependent signaling in tumors. Taken together, our results suggest that a small-molecule dual inhibitor of RON/c-Met has the potential to inhibit tumor growth and could therefore be useful for the treatment of patients with cancers where RON and/or c-Met are activated. [Cancer Res 2008;68(16):6680–7]
THE ENDOTHELIUM AS A TARGET FOR INFECTIONS
Authors: Gustavo Valbuena, David H. Walker
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

The endothelial cells lining vascular and lymphatic vessels are targets of several infectious agents, including viruses and bacteria, that lead to dramatic changes in their functions. Understanding the pathophysiological mechanisms that cause the clinical manifestations of those infections has been advanced through the use of animal models and in vitro systems; however, there are also abundant studies that explore the consequences of endothelial infection in vitro without supporting evidence that endothelial cells are actual in vivo targets of infection in human diseases. This article defines criteria for considering an infection as truly endothelium-targeted and reviews the literature that offers insights into the pathogenesis of human endothelial-target infections.
Differential Expression of Cardiac Biomarkers by Gender in Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Authors: Stephen D. Wiviott, Christopher P. Cannon, David A. Morrow, Sabina A. Murphy, C. Michael Gibson, Carolyn H. McCabe, Marc S. Sabatine, Nader Rifai, Robert P. Giugliano, Peter M. DiBattiste, Laura A. Demopoulos, Elliott M. Antman, Eugene Braunwald
Journal: Circulation (2004)

Background— Diagnosis of coronary artery disease in women is more difficult because of lower specificity of symptoms and diagnostic accuracy of noninvasive testing. We sought to examine the relationship between gender and cardiac biomarkers in patients with unstable angina (UA)/non–ST-segment elevation myocardial infarction (NSTEMI). Methods and Results— In the TACTICS-TIMI 18, OPUS-TIMI 16, and TIMI 11 studies, baseline samples were analyzed in the Thrombolysis In Myocardial Infarction (TIMI) biomarker core laboratory. We examined the relationship between gender and elevated biomarkers. Of 1865 patients from TACTICS-TIMI 18, 34% were women. Fewer women had elevated creatine kinase-MB or troponins, whereas more had elevated high-sensitivity C-reactive protein or brain natriuretic peptide. Presence of ST-segment deviation and TIMI risk scores were not significantly different. This pattern was confirmed in TIMI 11 and OPUS-TIMI 16. The prognostic value of the markers in TACTICS-TIMI 18 was similar in women and men. When a multimarker approach was examined, a greater proportion of high-risk women were identified. Marker-positive patients of both genders had improved outcome with an invasive strategy; however, marker-negative women appeared to have improved outcomes with a conservative strategy. Conclusions— In patients with UA/NSTEMI, there was a different pattern of presenting biomarkers. Men were more likely to have elevated creatine kinase-MB and troponins, whereas women were more likely to have elevated C-reactive protein and brain natriuretic peptide. This suggests that a multimarker approach may aid the initial risk assessment of UA/NSTEMI, especially in women. Further research is necessary to elucidate whether gender-related pathophysiological differences exist in presentation with acute coronary syndromes.
AN INVESTIGATION INTO THE TREATMENT OF ACNE VULGARIS WITH GRENZ X- RAYS
Authors: A. M. JELLIFFE, CHRISTINE SOUTTER, R. H. MEARA
Journal: British Journal of Dermatology (1969)

SUMMARY.— A controlled trial of Grenz rays in acne vulgaris failed to show any significant response to this treatment. More limited trials showed n29 KV x‐ray to be equally ineffective; 50 KV x‐ray appeared to be of some slight benefit, but the difference between treated and control sides of the face was small.
Evaluation of IL-10 level in serum and bronchoalveolar lavage fluid of patients with non-small cell lung cancer (NSCLC)
Authors: Marina Petrovic, Ivan Cekerevac, Gordana Kostic, Goran Davidovic, Violeta Iric-Cupic
Journal: European Respiratory Journal (2013)

AIM: To study the relationship between the interleukin-10 (IL-10) level in serum and broncheoalveolar lavage fluid (BALF) and non-small cell lung cancer (NSCLC). METHODS: The concentration of IL-10 in serum or BALF of 76 NSCLC patients, 43 patients of pulmonary inflammatory diseases (PID) and 24 normal controls were measured by ELISA. RESULTS: The concentration of IL-10 in BALF of NSCLC patients was significantly higher than that of PID patients and normal controls (P 0.05). Serum IL-10 level was higher in NSCLC of advanced stages (stage IIIa, IIIb and IV), as compared with that in NSCLC patients of early stages (stage Ia-IIb). BALF IL-10 level of NSCLC patients at different stages was not different. IL-10 (level in serum but not in BALF) of PID patients correlated with the serum concentration of C reactive protein (r=0.74). CONCLUSION: IL-10 in BALF might be used as a marker for NSCLC. Serum IL-10 level might be an indicator for the stage of NSCLC. The serum IL-10 can also reflect the severity of acute lung inflammatory response.
Modeling prognosis for patients with malignant astrocytic gliomas: Quantifying the expression of multiple genetic markers and clinical variables
Authors: Yi-Hong Zhou, Kenneth R. Hess, Longjian Liu, Mark. E. Linskey, W.K. Alfred Yung
Journal: Neuro-Oncology (2005)

The disparate lengths of survival among patients with malignant astrocytic gliomas (anaplastic astrocytomas [AAs] and glioblastoma multiforme [GBM]) cannot be adequately accounted for by clinical variables (patient age, histology, and recurrent status).Using real-time quantitative reverse transcription-polymerase chain reaction, we quantified the expression of four genes that were putative prognostic markers (CDK4, IGFBP2, MMP2, and RPS9) in a set of 43 AAs, 41 GBMs, and seven adjacent normal brain tissues.We previously explicated the expression and prognostic value of PAX6, PTEN, VEGF, and EGFR in these glioma tissues and Modeling prognosis for patients with malignant
Home environment and asthma in Kenyan schoolchildren: a case-control study.
Authors: N Mohamed, L Ng'ang'a, J Odhiambo, J Nyamwaya, R Menzies
Journal: Thorax (1995)

BACKGROUND--There is increasing evidence that environmental factors contribute to the development of asthma, so the relationship was studied between home environment factors and asthma among school children of varying socioeconomic backgrounds living in a developing country. METHODS--A case-control study was performed in participants of a prevalence survey which included 77 schoolchildren with asthma (defined by a history of wheeze, doctor diagnosis, or a decline in FEV1 of &gt; or = 10% at five or 10 minutes after exercise) and 77 age and gender matched controls. Subjects were selected from 402 school children aged 9-11 years attending five primary schools in the city of Nairobi who participated in a prevalence survey of asthma. Visits were made to the homes of cases and controls and visual inspection of the home environment was made using a checklist. A questionnaire regarding supplemental salt intake, parental occupation, cooking fuels, and health of all children in the family was administered by an interviewer. RESULTS--In multivariate analysis the following factors were associated with asthma: damage caused by dampness in the child9s sleeping area (adjusted odds ratio (OR) 4.9; 95% confidence interval (CI) 2.0 to 11.7), air pollution in the home (OR 2.5; 95% CI 2.0 to 6.4), presence of rugs or carpets in child9s bedroom (OR 3.6; 95% CI 1.5 to 8.5). Children with asthma reported a supplemental mean daily salt intake of 817 mg compared with 483 mg in controls. CONCLUSIONS--Home environmental factors appear to be strongly associated with asthma in schoolchildren in a developing nation. These findings suggest a number of hypotheses for further studies.
Role of interleukin-10 in T helper cell dysfunction in asymptomatic individuals infected with the human immunodeficiency virus.
Authors: M Clerici, T A Wynn, J A Berzofsky, S P Blatt, C W Hendrix, A Sher, R L Coffman, G M Shearer
Journal: Journal of Clinical Investigation (1994)

The loss of T helper cell (TH) function in asymptomatic HIV type 1-infected individuals occurs before the decline in CD4+ T cells. At least part of the loss in TH function results from changes in immunoregulatory cytokine profiles. To investigate the role of IL-10 in such dysregulation, we tested whether: (a) expression of IL-10-specific mRNA would be upregulated in PBMC from asymptomatic, HIV-infected (HIV+) individuals; (b) PBMC from these same individuals would produce increased levels of IL-10 when stimulated in vitro with phytohemagglutinin; and (c) defective antigen-specific TH function could be restored by anti-IL-10 antibody. We observed that IL-10-specific mRNA was marginally upregulated, and increased levels of IL-10 were produced by PBMC from HIV+ individuals compared with PBMC from uninfected individuals. Those individuals whose TH function was more severely compromised produced higher levels of IL-10. Additionally, defective antigen-specific TH function in vitro could be reversed by anti-IL-10 antibody, including the response to HIV envelope synthetic peptides. Furthermore, the antigen-specific TH responses of HIV-uninfected PBMC could be reduced with IL-10, a process reversed by anti-IL-10. These results confirm that the early loss of TH function in HIV+ individuals is due at least in part to cytokine-induced immune dysregulation, and support the hypothesis of a switch from a predominant type 1 state to a predominant type 2 condition in HIV infection.
Late Cardiac Effects of Adjuvant Chemotherapy in Breast Cancer Survivors Treated on Southwest Oncology Group Protocol S8897
Authors: Patricia A. Ganz, Michael A. Hussey, Carol M. Moinpour, Joseph M. Unger, Laura F. Hutchins, Shaker R. Dakhil, Jeffrey K. Giguere, J. Wendall Goodwin, Silvana Martino, Kathy S. Albain
Journal: Journal of Clinical Oncology (2008)

Purpose The late cardiac effects of adjuvant anthracycline therapy in survivors of early-stage breast cancer have had limited study. Subclinical and clinical cardiac late effects may contribute to added comorbidity over time. Patients and Methods We recruited patients treated on Southwest Oncology Group (SWOG) protocol S8897 who had been randomly assigned to adjuvant chemotherapy with or without doxorubicin. Left ventricular ejection fraction (LVEF) was evaluated at 5 to 8 years and 10 to 13 years after treatment randomization. Cardiac risk factors and events were reported by clinicians annually between the two assessments. Results A total of 180 breast cancer survivors from a potential sample of 1,176 patients were entered, 163 patients at 5 to 8 years and 17 additional patients at 10 to 13 years, with 93 longitudinal assessments of LVEF. There was no significant difference in the proportion of women with an LVEF less than 50% at 5 to 8 (cyclophosphamide, doxorubicin, and fluorouracil [CAF] v cyclophosphamide, methotrexate, and fluorouracil [CMF]: 5% v 7%; P = .68) or 10 to 13 years (CAF v CMF: 3% v 0%; P = .16); however, in an exploratory analysis, the mean LVEF in the doxorubicin group was statistically significantly lower in the 5- to 8-year sample (64.8% v 61.4%; P = .01) but not in the 10- to 13-year sample. In the longitudinal analysis, there was no significant deterioration in LVEF. Conclusion Women enrolled onto an adjuvant chemotherapy treatment clinical trial for breast cancer were successfully recruited to participate in a research study of the late effects of treatment, although many SWOG institutions and potentially eligible patients chose not to participate. In this selected sample, with up to 13 years of follow-up, exposure to doxorubicin did not increase the likelihood of adverse cardiac effects.
The MUC13 cell-surface mucin protects against intestinal inflammation by inhibiting epithelial cell apoptosis
Authors: Y. H. Sheng, R. Lourie, S. K. Linden, P. L. Jeffery, D. Roche, T. V. Tran, C. W. Png, N. Waterhouse, P. Sutton, T. H. J. Florin, M. A. McGuckin
Journal: Gut (2011)

The MUC13 transmembrane mucin is highly and constitutively expressed in the small and large intestine. Although MUC13 polymorphisms have been associated with human inflammatory bowel diseases and susceptibility to Escherichia coli infection in pigs, the biological functions of MUC13 are unknown. This study aimed to explore whether MUC13 modulates intestinal inflammation.Muc13(-/-) mice were generated, phenotyped and challenged with the colitis-inducing agent, dextran sodium sulphate (DSS). Colitis was assessed by clinical symptoms and intestinal histopathology. Intestinal epithelial cell apoptosis and proliferation, macrophage infiltration and cytokine production were also quantified. Apoptosis of human LS513 intestinal epithelial cells in response to apoptotic agents, including DSS, was also measured, following knockdown of MUC13 with siRNA.Muc13(-/-) mice were viable, fertile and developed normally, with no spontaneous intestinal pathology except mild focal neutrophilic inflammation in the small and large intestines of old mice. In response to DSS challenge, Muc13(-/-) mice developed more severe acute colitis, as reflected by increased weight loss, rectal bleeding, diarrhoea and histological colitis scores compared with wild-type mice. Increased numbers of F4/80(+) macrophages in inflamed mucosa of Muc13(-/-) mice were accompanied by increased expression of intestinal IL-1β and TNFα mRNA. Muc13(-/-) mice had significantly increased intestinal epithelial cell apoptosis within 3 days of DSS exposure. LS513 cells were more susceptible to DSS, actinomycin-D, ultraviolet irradiation and TRAIL-induced apoptosis when MUC13 was knocked down by siRNA.These novel findings indicate a protective role for Muc13 in the colonic epithelium by inhibiting toxin-induced apoptosis and have important implications for intestinal infections, inflammatory diseases and the development of intestinal cancer.
Perspectives of Patients With Schizophrenia and Psychiatrists Regarding Ethically Important Aspects of Research Participation
Authors: Laura Weiss Roberts, Teddy D. Warner, Janet L. Brody
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Significant controversy surrounds the ethics of psychiatric research. Nevertheless, few data have been gathered to improve our understanding of how individuals with serious mental illness and psychiatrists view ethically important aspects of biomedical research participation. METHOD: The authors assessed views of clinically diagnosed patients with schizophrenia from three sites by means of structured interviews and views of psychiatrists at two sites with written surveys regarding attitudes affecting motivation to participate in biomedical research, attitudes related to autonomy and influences on participation decisions, and attitudes toward the inclusion of vulnerable populations in research. The schizophrenia patients were asked to indicate their personal views; the psychiatrists were asked to provide their personal views and to predict schizophrenia patients' views. Responses were compared by using repeated measures multivariate analysis of variance. RESULTS: Sixty-three patients with schizophrenia and 73 psychiatry faculty and residents participated. Overall, responses to 23 rated attitudes revealed remarkably similar rank orders and several areas of agreement between patients and psychiatrists. Both groups strongly supported schizophrenia research and autonomous decision making by participants. They saw helping others and helping science as important reasons for protocol participation. Patients endorsed the feeling of hope associated with research involvement, a perspective underestimated by psychiatrists. Psychiatrists also underestimated the patients' acceptance of physician, investigator, and family influences on participation decisions. Psychiatrists agreed more strongly than patients that vulnerable populations should be included in research. CONCLUSIONS: This study helps to characterize previously neglected attitudes of psychiatric patients and clinicians toward ethically important aspects of biomedical research participation. Schizophrenia patients offered highly discerning views, and interesting similarities and differences emerged in comparing responses of patients and psychiatrists.
Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling
Authors: Chandran Vijayendran, Aiko Barsch, Karl Friehs, Karsten Niehaus, Anke Becker, Erwin Flaschel
Journal: Genome biology (2008)

Evolutionary changes that are due to different environmental conditions can be examined based on the various molecular aspects that constitute a cell, namely transcript, protein, or metabolite abundance. We analyzed changes in transcript and metabolite abundance in evolved and ancestor strains in three different evolutionary conditions - excess nutrient adaptation, prolonged stationary phase adaptation, and adaptation because of environmental shift - in two different strains of bacterium Escherichia coli K-12 (MG1655 and DH10B). Metabolite profiling of 84 identified metabolites revealed that most of the metabolites involved in the tricarboxylic acid cycle and nucleotide metabolism were altered in both of the excess nutrient evolved lines. Gene expression profiling using whole genome microarray with 4,288 open reading frames revealed over-representation of the transport functional category in all evolved lines. Excess nutrient adapted lines were found to exhibit greater degrees of positive correlation, indicating parallelism between ancestor and evolved lines, when compared with prolonged stationary phase adapted lines. Gene-metabolite correlation network analysis revealed over-representation of membrane-associated functional categories. Proteome analysis revealed the major role played by outer membrane proteins in adaptive evolution. GltB, LamB and YaeT proteins in excess nutrient lines, and FepA, CirA, OmpC and OmpA in prolonged stationary phase lines were found to be differentially over-expressed. In summary, we report the vital involvement of energy metabolism and membrane-associated functional categories in all of the evolutionary conditions examined in this study within the context of transcript, outer membrane protein, and metabolite levels. These initial data obtained may help to enhance our understanding of the evolutionary process from a systems biology perspective.