tbuckley/cabot-search huggingface dataset:
The Power-Velocity Integral at the Vena Contracta
Authors: Thomas Buck, Ronald A. Mucci, J. Luis Guerrero, Godtfred Holmvang, Mark D. Handschumacher, Robert A. Levine
Journal: Circulation (2000)

Background —Noninvasive quantification of regurgitation is limited because Doppler measures velocity, not flow. Because backscattered Doppler power is proportional to sonified blood volume, power times velocity should be proportional to flow rate. Early studies, however, suggested that this held only for laminar flow, not for regurgitant jets, in which turbulence and fluid entrainment augment scatter. We therefore hypothesized that this Doppler power principle can be applied at the proximal vena contracta, where flow is laminar before entrainment, so that the power-times-velocity integral should vary linearly with flow rate and its time integral with stroke volume (SV). Methods and Results —This was tested in vitro with steady and pulsatile flow through 0.07- to 0.8-cm 2 orifices and in 36 hemodynamic stages in vivo, replacing the left atrium with a rigid chamber and column for direct visual recording of mitral regurgitant SV (MRSV). In 12 patients, MRSV was compared with MRI mitral inflow minus aortic outflow and in 11 patients with 3D echo left ventricular ejection volume–Doppler aortic forward SV. Vena contracta power in the narrow high-velocity spectrum from a broad measuring beam was calibrated against that from a narrow reference beam of known area. Calculated and actual flow rates and SV correlated well in vitro ( r =0.99, 0.99; error=−1.6±2.5 mL/s, −2.4±2.9 mL), in vivo (MRSV: r =0.98, error=0.04±0.87 mL), and in patients (MRSV: r =0.98, error=−2.8±4.5 mL). Conclusions —The power-velocity integral at the vena contracta provides an accurate direct measurement of regurgitant flow, overcoming the limitations of existing Doppler techniques.
Clinical Lectures on Certain Diseases of the Chest
Authors: A. T. H. Waters
Journal: BMJ (1867)

GENTLEMEN,-In my last lecture, I pointed out to you the modes of treatment which I think are most to be depended on in cases of pneu- monia; and I now wish to draw your attention to the details of some cases in which the principles I have referred to have been practically ap- plied.There is one circumnstance to which I have not specially alluded, but which is of much importance in reference to the treatment of this disease; viz., the constitutional condition of the patients who are attacked by it.There can be no doubt that in many patients there has been some deterioration of health which has acted as the predisposing cause of the disease; but, at .the same time, .it is quite certain that cases occa- sionally occur in which there has been no previous ill-health.In such patients, exposure to wet or to cold, or to both, has been the ex- citing cause of the attack.Instances of this kind we sometimes meet with in our wards, in strong, active labourers or seamen, who are sud- denly struck down by the disease.At the same time, I believe that in private practice you will very.rarelymeet with such cases.Most of those attacked with pneumonia, whom 'you will be called upon to treat in private practice, and especially the more wealthy of your patients, will be people not exposed to great hardships, nor to the inclemencies of the weather; .andin.these persons you will generally be able to trace some antecedent depressing circumstances,, some deterioration of health, or some organic disease which has predisposed to the pneumonic attack.
Tumor Spheroids as an In Vitro Model for Determining the Therapeutic Response to Proton Beam Radiotherapy and Thermally Sensitive Nanocarriers
Authors: Lakmini K. Senavirathna, Ruchika Fernando, Danny Maples, Yuanshui Zheng, Jerimy C. Polf, Ashish Ranjan
Journal: Theranostics (2013)

Multicellular Tumor Spheroids (MCTS) strongly resemble tumor tissues, which makes them useful tools for radiation biology studies and screening of various chemotherapeutics.The goal of this pilot study was to use MCTS as an in vitro model to determine the response of cells to low temperature-sensitive liposomes (LTSLs) encapsulating doxorubicin (Dox) and proton beam radiotherapy (PBRT).Prior to treatment, MCTS were characterized for morphology and LTSLs were characterized for size, encapsulation efficiency, and ability to thermally release Dox (a model anticancer agent).Two groups of MCTS were treated with LTSL in combination with mild hyperthermia (40-42 °C) or PBRT alone in the presence of appropriate controls.Cytotoxic response was assessed after 48-72 h using an acid phosphatase assay.At 72 h, LTSL in combination with heat significantly reduced the viability of MCTS (15-30%) compared to the control (P < 0.05).A similar cytotoxic response was observed with PBRT treatment.The data suggest that like a monolayer cell culture, MCTS can be used to determine cytotoxic outcomes of thermal and proton therapy.
Plasma Vitamin D Concentration and Survival in Colorectal Cancer: Potential Confounding by the Systemic Inflammatory Response
Authors: Fiona J.S. Conway, Donald C. McMillan
Journal: Journal of Clinical Oncology (2014)

TO THE EDITOR: We read with interest the work of Zgaga et al, entitled, “Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer,” that was recently published in Journal of Clinical Oncology. They prospectively studied 1,598 patients diagnosed with stage I to III colorectal cancer (CRC) undergoing intended curative resection and examined the relationship between postoperative plasma 25 hydroxyvitamin D (plasma 25[OH]D) concentrations and survival. They concluded that higher plasma 25(OH)D concentrations were associated with better outcomes in both cancer-specific and overall survival. However, some have questioned a putative role for vitamin D in chronic disease outcomes. Indeed, the authors acknowledge the potential for confounding factors and include a number of environmental factors known to influence plasma 25(OH)D concentrations in their analysis. Disappointingly, despite citing an article that shows the important confounding effect of the systemic inflammatory response (SIR) and repeated reports in the literature that markers of the SIR such as C-reactive protein and albumin are independently associated with plasma 25(OH)D concentrations they did not include a marker of the SIR in their analysis. Indeed, a plausible interpretation of their results would be that the low plasma 25(OH)D concentrations were the result of an ongoing SIR since there is a recognized association between the presence of the SIR and poor outcome in patients with cancer. Of course the veracity of such an explanation can be simply tested by including measures of the SIR in the analysis. We urge the authors to do this and report their findings. Irrespectively, until appropriate randomized controlled trial data are available, data of the type presented by the authors should be interpreted with caution.
Studies of the antibody-dependent killing of schistosomula of Schistosoma mansoni employing haptenic target antigens. I. Evidence that the loss in susceptibility to immune damage undergone by developing schistosomula involves a change unrelated to the masking of parasite antigens by host molecules.
Authors: G Moser, D L Wassom, A Sher
Journal: The Journal of Experimental Medicine (1980)

A method was developed for coupling a hapten, trinitrophenyl (TNP), to the surface of schistosomula of Schistosoma mansoni which results in a minimal loss in their viability as judged by morphological examination in vitro and survival after injection in vivo. Skin-stage (3-h-old) and lung-stage (5-d-old) schistosomula surface labeled in this manner were then compared for their susceptibility to killing by anti-TNP antibody-dependent effector mechanisms both in vivo and in vitro. TNP skin-stage larvae were readily rejected in mice actively immunized against TNP bovine gamma globulin and were highly susceptible to anti-TNP-dependent killing mediated either by complement or purified human eosinophils in vitro. In contrast, TNP-lung-stage schistosomula, which were shown by microfluorimetry to bind anti-TNP antibody to approximately the same extent as skin-stage schistosomula, were found to be resistant to killing by the same in vivo and in vitro mechanisms. These findings suggest that the insusceptibility of postskin-stage schistosomula to antibody-dependent killing must result at least in part from an intrinsic structural change in the integument of the parasite and cannot be caused solely by the masking of parasite antigens by acquired host molecules, a mechanism of immune evasion previously proposed for schistosomes.
Acute Hemodynamic Effects of Conivaptan, a Dual V <sub>1A</sub> and V <sub>2</sub> Vasopressin Receptor Antagonist, in Patients With Advanced Heart Failure
Authors: James E. Udelson, William B. Smith, Grady H. Hendrix, Christopher A. Painchaud, Maha Ghazzi, Ignatius Thomas, Jalal K. Ghali, Paulina Selaru, Francoise Chanoine, Milton L. Pressler, Marvin A. Konstam
Journal: Circulation (2001)

Background Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V 1A (vascular and myocardial effects) and V 2 receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. Methods and Results A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V 1a /V 2 vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (−2.6±0.7, −5.4±0.7, and −4.6±0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P &lt;0.05) and right atrial pressure (−2.0±0.4, −3.7±0.4, and −3.5±0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P &lt;0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (−11±17, 68±17, 152±19, and 176±18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P &lt;0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. Conclusions In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.
Mechanism of effector-cell blockade. I. Antigen-induced suppression of Ig synthesis in a hybridoma cell line, and correlation with cell-associated antigen.
Authors: A W Boyd, J W Schrader
Journal: The Journal of Experimental Medicine (1980)

A mouse hybridoma cell line, FluIgM-1, which secretes IgM specific for the hapten fluorescein (FLU) was developed to allow detailed analysis of the effector-cell blockade (ECB) phenomenon, in which contact of antibody-forming cells (AFC) with specific antigen results in marked reduction of antibody secretion. Treatment of hybridoma cells with highly substituted FLU conjugates (e.g., Flu20gelatin) resulted in inhibition of plaque formation. The data indicated close parallels with the ECB of normal spleen AFC, both in speed of onset and the dose of antigen required. The inhibition of antibody secretion was confirmed with a biosynthetic-labeling procedure which demonstrated that this was a result of reduced Ig synthesis. The inhibitory effect appeared to be confined to antibody synthesis, in the total protein synthesis, DNA synthesis, and cell-doubling times were unaffected. The association of FLU conjugates with the cells during and following ECB was studied directly using fluorescence microscopy and the fluorescence-activated cell sorter. These experiments showed that FLU conjugates capable of causing blockade aggregated on the cell surface, that the clearance of cell-associated antigen correlated with recovery from ECB, and that at all times when cell associated antigen was detectable, a portion remained bound to the cell surface and was susceptible to enzymatic removal. The latter observations supported previous findings suggesting that ECB was mediated by extracellular antigen. The direct observation of aggregates of antigen on the surface of blockaded cells is consistent with a mechanism involving cross-linking of Ig receptors. Finally, Fc receptors were not present on hybridoma cells, excluding their involvement in induction of ECB.
Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer
Authors: Nassima Redjimi, Françoise Gaudin, Cyril Touboul, Dominique Emilie, Marc Pallardy, Armelle Biola-Vidamment, Hervé Fernandez, Sophie Prévot, Karl Balabanian, Véronique Machelon
Journal: Molecular Cancer (2009)

Abstract Background Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC), currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ), an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation. Results GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, P &lt; 0.00001, r = 0.56). They were also higher in tumor cells containing large amounts of phosphorylated protein kinase B (p-AKT) (unpaired t test, P &lt; 0.0001). To assess the effect of GILZ on proliferation and AKT activation, we used the BG-1 cell line derived from ovarian tumor cells as a cellular model. GILZ expression was either enhanced by stable transfection or decreased by the use of small interfering (si) RNA targeting GILZ. We found that GILZ increased cell proliferation, phospho-AKT cellular content and AKT kinase activity. Further, GILZ upregulated cyclin D1 and phosphorylated retinoblastoma (p-Rb), downregulated cyclin-dependent kinase inhibitor p21, and promoted the entry into S phase of cell cycle. Conclusion The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.
Concordance Between Local and Central Laboratory HER2 Testing in the Breast Intergroup Trial N9831
Authors: P. C. Roche, V. J. Suman, R. B. Jenkins, N. E. Davidson, S. Martino, P. A. Kaufman, F. K. Addo, B. Murphy, J. N. Ingle, E. A. Perez
Journal: JNCI Journal of the National Cancer Institute (2002)

The efficacy of trastuzumab for metastases coupled with the relatively poor prognosis of patients with node-positive, HER2-positive breast cancer has led to the evaluation of trastuzumab as an adjuvant therapy. A prospective, randomized, three-arm, phase III trial is being conducted by the Breast Intergroup (N9831) for women with primary, operable, histologically confirmed, node-positive breast carcinoma that strongly overexpresses (3+) HER2 protein and/or displays HER2/neu gene amplification, as determined by local laboratory testing. The protocol requires confirmatory central testing of HER2 status using the HercepTestTM immunohistochemistry and the Vysis PathVysionTM fluorescence in situ hybridization (FISH) assays. Tumor specimens from the first 119 patients enrolled in N9831 were centrally tested; 74% were found to be HercepTestTM 3+ and 66% were found to have HER2 gene amplification. Only six of nine (67%) of the specimens submitted by local laboratories as FISH positive could be confirmed by central assays. The concordance for central HercepTestTM and central FISH assays was 92%. The poor concordance (74%) between local and central testing for HER2 status has led to modifications in the eligibility criteria for N9831.
Overcoming Barriers in Cancer Pain Management
Authors: Jung Hye Kwon
Journal: Journal of Clinical Oncology (2014)

Pain is a devastating symptom of cancer that affects the quality of life of patients, families, and caregivers. It is a multidimensional symptom that includes physical, psychosocial, emotional, and spiritual components. Despite the development of novel analgesics and updated pain guidelines, cancer pain remains undermanaged, and some patients with moderate to severe pain do not receive adequate pain treatment. Inadequate pain management can be attributed to barriers related to health care professionals, patients, and the health care system. Common professional-related barriers include poor pain assessment, lack of knowledge and skill, and the reluctance of physicians to prescribe opioids. Patient-related barriers include cognitive factors, affective factors, and adherence to analgesic regimens. System-related barriers such as limits on access to opioids and the availability of pain and palliative care specialists present additional challenges, particularly in resource-poor regions. Given the multidimensional nature of cancer pain and the multifaceted barriers involved, effective pain control mandates multidisciplinary interventions from interprofessional teams. Educational interventions for patients and health care professionals may improve the success of pain management.
Effects of Bone-Targeted Agents on Cancer Progression and Mortality
Authors: R. Coleman, M. Gnant, G. Morgan, P. Clezardin
Journal: JNCI Journal of the National Cancer Institute (2012)

Bone-targeted treatments with bisphosphonates and denosumab, which reduce bone resorption, are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the "vicious cycle" of growth factor and cytokine signaling between tumor and bone cells within the bone marrow microenvironment. Effects of the drugs on the stem cell niche, direct effects on the cancer cells, and immune modulation may also contribute. In early-stage (stages I, II, and III) breast cancer, treatment with the bisphosphonate zoledronic acid has shown improvements in disease-free and overall survival. Improved survival was particularly notable in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease who received treatment with goserelin, which suppresses ovarian function by inhibiting the production of ovarian hormones. Additionally, in castrate-resistant prostate cancer, treatment with denosumab delays the development of bone metastases. These results strongly support the adjuvant use of bone-targeted treatments but suggest that reproductive hormones are an important treatment modifier to take into account. In advanced-stage (stage IV, ie, metastatic) cancers, survival benefits have been observed in patients with multiple myeloma and in patients with other solid tumors with rapid rates of bone destruction who received treatment with zoledronic acid. Here, we have critically reviewed the increasing evidence to support a disease-modifying effect of bone-targeted treatment and discussed the impact on clinical management.
Psychological, Behavioral, and Immune Changes After a Psychological Intervention: A Clinical Trial
Authors: Barbara L. Andersen, William B. Farrar, Deanna M. Golden-Kreutz, Ronald Glaser, Charles F. Emery, Timothy R. Crespin, Charles L. Shapiro, William E. Carson
Journal: Journal of Clinical Oncology (2004)

This randomized clinical trial tests the hypothesis that a psychological intervention can reduce emotional distress, improve health behaviors and dose-intensity, and enhance immune responses.We studied 227 women who were surgically treated for regional breast cancer. Before adjuvant therapy, women completed interviews and questionnaires assessing emotional distress, social adjustment, and health behaviors. A 60-mL blood sample was drawn for immune assays. Patients were randomly assigned to either the intervention group or assessment only group. The intervention was conducted in small patient groups, with one session per week for 4 months. The sessions included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment and care. Reassessment occurred after completion of the intervention.As predicted, patients receiving the intervention showed significant lowering of anxiety, improvements in perceived social support, improved dietary habits, and reduction in smoking (all P <.05). Analyses of adjuvant chemotherapy dose-intensity revealed significantly more variability (ie, more dispersion in the dose-intensity values) for the assessment arm (P <.05). Immune responses for the intervention patients paralleled their psychological and behavioral improvements. T-cell proliferation in response to phytohemagglutinin and concanavalin A remained stable or increased for the Intervention patients, whereas both responses declined for Assessment patients; this effect was replicated across three concentrations for each assay (all P <.01).These data show a convergence of significant psychological, health behavior, and biologic effects after a psychological intervention for cancer patients.
A New Antigen Recognized by Cytolytic T Lymphocytes on a Human Kidney Tumor Results from Reverse Strand Transcription
Authors: Benoît J. Van den Eynde, Béatrice Gaugler, Michael Probst-Kepper, Lucienne Michaux, Olivier Devuyst, Francis Lorge, Patrick Weynants, Thierry Boon
Journal: The Journal of Experimental Medicine (1999)

By stimulating blood lymphocytes from a renal cell carcinoma patient in vitro with the autologous tumor cells, we obtained cytolytic T lymphocyte (CTL) clones that killed several autologous and allogeneic histocompatibility leukocyte antigen (HLA)-B7 renal carcinoma cell lines. We identified the target antigen of these CTLs by screening COS cells transfected with the HLA-B7 cDNA and with a cDNA library prepared with RNA from the tumor cells. The antigenic peptide recognized by the CTLs has the sequence LPRWPPPQL and is encoded by a new gene, which we named RU2. This gene is transcribed in both directions. The antigenic peptide is not encoded by the sense transcript, RU2S, which is expressed ubiquitously. It is encoded by an antisense transcript, RU2AS, which starts from a cryptic promoter located on the reverse strand of the first intron and ends up on the reverse strand of the RU2S promoter, which contains a polyadenylation signal. This mechanism of antigen expression is unprecedented and further illustrates the notion that many peptides recognized by T cells cannot be predicted from the primary structure of the major product of the encoding gene. Antisense transcript RU2AS is expressed in a high proportion of tumors of various histological types. It is absent in most normal tissues, but is expressed in testis and kidney, and, at lower levels, in urinary bladder and liver. Short-term cultures of normal epithelial cells from the renal proximal tubule expressed significant levels of RU2AS message and were recognized by the CTLs. Therefore, this antigen is not tumor specific, but corresponds to a self-antigen with restricted tissue distribution.