tbuckley/cabot-search huggingface dataset:
Effects of inhalation of an artificial fog
Authors: J. D. Abernethy
Journal: Thorax (1968)

Atmospheric fog plays some role in the production of symptoms in chronic bronchitis, but hitherto the blame has rested with pollutants rather than with the water droplet content itself. An investigation of the effects of an artificial water-containing fog at room temperature on the F.E.V.<sub>1·0</sub> of seven patients with chronic bronchitis showed a significant reduction (mean 17·9%) as compared with a minimal or absent effect in seven out of eight normal subjects. The effect tended to persist in sensitive subjects but could be reversed by a bronchodilator. Additional experiments measuring airways resistance, total pulmonary resistance, and static and dynamic compliance tended to support the hypothesis that the fog effect is due to reflex bronchoconstriction. I suggest that water droplets, each having a finite momentum, initiate the reflex in the same manner as dust particles. Although these experiments were confined to large doses inhaled for brief intervals, it is possible that the presence of water droplets alone would increase the morbidity from atmospheric fog. Epidemiological studies on the effects of fog should include direct measurement of the water droplet content. Therapeutic aerosols might also produce this adverse effect.
Systematic Review of Quality Improvement Interventions Directed at Cancer Specialists
Authors: Michael Coory, Victoria M. White, Kristin S. Johnson, David J. Hill, Michael Jefford, Simon Harrison, Ingrid Winship, Jeremy Millar, Graham G. Giles
Journal: Journal of Clinical Oncology (2013)

Summary evidence on the effectiveness of quality improvement interventions (QIIs) directed at cancer specialists is needed for two reasons. First, there are some innovations over which only cancer specialists have control (eg, surgical technique or chemotherapy regimen). Second, implementation of QIIs has opportunity costs; the time and money spent on an ineffective QII might be better spent on direct patient care.Medical Subject Headings and text words for "quality improvement" were combined with those for "neoplasm" to search MEDLINE, PsycINFO, CINAHL, and EMBASE from January 1990 to August 2012 for studies of QIIs directed at cancer specialists (eg, medical/radiation oncologist, surgeon). All study designs were included.Five thousand seven hundred eighty-one articles were screened, but only 12 met the inclusion criteria, including three cluster randomized controlled trials (cRCTs), seven uncontrolled before-and-after comparisons, and two cross-sectional studies. All 12 studies were conducted in response to concerns about quality of care. No cRCT showed a benefit of the QIIs tested. Some uncontrolled before-and-after and cross-sectional studies reported a benefit from the QII, but these studies are difficult to interpret because of concerns about uncontrolled confounding. Interventions in all studies were multifaceted, but descriptions of different components were limited, and only one study examined their separate impact.The published evidence about how to facilitate timely and consistent adoption of new clinical knowledge by cancer specialists into everyday clinical practice is thin. More investment is needed in research about the solution (QIIs) to match the investment in research about the problem (inconsistent/slow adoption of innovative cancer treatments).
Role of Plasma Vasopressin in Impaired Water Excretion of Glucocorticoid Deficiency
Authors: John Boykin, Antoine Detorrenté, Abby Erickson, Gary Robertson, Robert W. Schrier
Journal: Journal of Clinical Investigation (1978)

In the present study, the effect of selective glucocorticoid deficiency on renal water excretion was investigated in conscious, trained, adrenalectomized dogs. The animals were studied before and after a water load while on replacement therapy of desoxycorticosterone acetate, 5 mg/day, and dexamethasone, 0.8 mg/day (group I), and while off dexamethasone for 5-9 days (group II). Before the water load the weight, inulin space, cardiac output, blood pressure, glomerular filtration rate, renal blood flow, plasma osmolality, and plasma antidiuretic hormone measured by radioimmunoassay were similar in both groups I and II. However, after a 40 ml/kg water load a marked impairment in renal water excretion in the glucocorticoid deficient dogs became apparent. Maximal free water clearance was -0.046+/-0.16 vs. 6.51+/-0.72 ml/min (P < 0.001) and minimal urinary osmolality was 425+/-56 vs. 82+/-3.5 mosmol/kg H(2)O (P < 0.001) in group II as compared to group I. Plasma antidiuretic hormone was maximally suppressed during the water load in group I to 0.34+/-0.08 pg/ml but remained elevated at 9.18+/-1.79 pg/ml (P < 0.005) in group II. This nonsuppressibility of plasma antidiuretic hormone during water loading in group II was associated with a significant tachycardia of 145+/-6 vs. 87+/-6 beats/min (P < 0.001) in group I and a significantly lower stroke volume of 27+/-0 vs. 59+/-0.5 ml/beat (P < 0.001). In conclusion, our results implicate a persistent secretion of antidiuretic hormone as an important factor in the impaired water excretion of glucocorticoid deficiency. A deleterious effect of glucocorticoid deficiency on cardiac function was observed and this hemodynamic alteration could be involved in initiating a nonosmolar, baroreceptor-mediated release of vasopressin.
IP-10 Blocks Vascular Endothelial Growth Factor-Induced Endothelial Cell Motility and Tube Formation via Inhibition of Calpain
Authors: Richard J. Bodnar, Cecelia C. Yates, Alan Wells
Journal: Circulation Research (2006)

Angiogenesis plays a critical role in wound repair. Endothelial cells present CXC receptor 3 (CXCR3) for chemokines expressed late in wound regeneration. To understand the physiological role CXCR3 plays in regulating endothelial function, we analyzed the ability of a CXCR3 ligand, IP-10 (CXCL10), to influence endothelial cell tube formation. Treatment of endothelial cells with IP-10 in the presence of vascular endothelial growth factor (VEGF) inhibited tube formation on growth factor-reduced Matrigel and in a subcutaneous Matrigel plug. Furthermore, IP-10 significantly inhibited VEGF-induced endothelial motility, a response critical for angiogenesis. Previous work showed that CXCR3 ligandation initiates protein kinase A (PKA) phosphorylation-dependent inhibition of m-calpain, required for induced cell motility, in fibroblasts but not epithelial cells. Here we show that CXCR3 activation in endothelial cells induces an increase in cAMP and PKA activation. Treatment of endothelial cells with Rp-8-Br-cAMP, an inhibitor of PKA, or small interference RNA to PKA was able to reverse the inhibitory effects of IP-10 on VEGF-mediated tube formation and motility. Importantly, treatment of endothelial cells with VEGF induced the activation of m-calpain, but costimulation with IP-10 significantly decreased this activity. Using Rp-8-Br-cAMP, we show blocking PKA reversed the IP-10 inhibition of VEGF-induced m-calpain activity. These data indicate that the activation of CXCR3 inhibits endothelial tube formation through a PKA mediated inhibition of m-calpain. This provides a means by which late wound repair signals limit the angiogenesis driven early in the wound response process.
XBP-1 image overhaul
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

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Electron micrograph of a mature plasma cell showing extensive endoplasmic reticulum. Reproduced from Bosman et al. (1969. J. Exp. Med. 129:1029–1044).The development of antibody-secreting plasma cells is crippled in the absence of the transcription factor XBP-1 (X-box
Are Peroxisome Proliferator-Activated Receptors Involved in Skeletal Muscle Wasting during Experimental Cancer Cachexia? Role of β2-Adrenergic Agonists
Authors: Gemma Fuster, Sílvia Busquets, Elisabet Ametller, Mireia Olivan, Vanessa Almendro, Cibely Cristine Fontes de Oliveira, Maite Figueras, Francisco J. López-Soriano, Josep M. Argilés
Journal: Cancer Research (2007)

Abstract Implantation of the Yoshida AH-130 ascites hepatoma to rats resulted in a decrease in muscle weight 7 days after the inoculation of the tumor. These changes were associated with increases in the mRNA content for both peroxisome proliferator-activated receptor (PPAR) γ and PPARδ in skeletal muscle. The increase in gene expression for these transcription factors was related to increases in the expression of several genes involved in fatty acid transport, activation, and oxidation. Tumor burden also resulted in increases in PPARγ coactivator-1α gene expression and pyruvate dehydrogenase kinase 4. All these changes in lipid metabolism genes suggest that a metabolic shift occurs in skeletal muscle of tumor-bearing rats toward a more oxidative phenotype. Formoterol treatment to tumor-bearing rats resulted in an amelioration of all the changes observed as a result of tumor burden. Administration of this β2-adrenergic agonist also resulted in a decrease in mRNA content of muscle PPARα, PPARδ, and PPARγ, as well as in mRNA levels of many of the genes involved in both lipid and mitochondrial metabolism. All these results suggest an involvement of the different PPARs as transcription factors related with muscle wasting and also indicate that a possible mode of action of the anticachectic compound formoterol may involve a normalization of the levels of these transcription factors. [Cancer Res 2007;67(13):6512–9]
The Penetration of Anticancer Drugs through Tumor Tissue as a Function of Cellular Adhesion and Packing Density of Tumor Cells
Authors: Rama Grantab, Shankar Sivananthan, Ian F. Tannock
Journal: Cancer Research (2006)

To reach cancer cells in optimal quantities, therapeutic agents must be delivered to tumors through their imperfect blood vascular system, cross vessel walls into the interstitium, and penetrate multiple layers of tissue. Strategies to enhance drug penetration have potential to improve therapeutic outcome. The development of multicellular layers (MCLs), in which tumor cells are grown on a semipermeable Teflon support membrane, has facilitated quantification of drug penetration through solid tissue. The goals of the present study were to quantify the penetration of anticancer drugs as a function of cellular adhesion and packing density and to determine the effects of variable penetration on therapeutic efficacy in this model system. We compared the properties of MCLs grown from two epithelioid and round subclones of a colon carcinoma cell line. One pair of epithelioid and round sublines differed in expression of alpha-E-catenin, and both pairs generated MCLs with different packing density. The penetration of commonly used anticancer agents (paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil) through MCLs derived from these cell lines was significantly greater through the round (loosely packed) than through the epithelioid (tightly packed) sublines. In MCLs treated with doxorubicin, we observed greater survival in the tightly packed cell lines than in the loosely packed cell lines. Impaired penetration of anticancer agents through MCLs derived from the tightly packed cell lines and relative resistance to killing of cells within them by doxorubicin treatment strengthen the role of tumor cell adhesion and packing density as contributing to drug resistance.
F-18 Fluorodeoxyglucose Positron Emission Tomography in Pulmonary Cryptococcoma
Authors: Chung-Huei Hsu, Chi-Ming Lee, Fong-Chieh Wang, Yun-Ho Lin
Journal: Clinical Nuclear Medicine (2003)

Cryptococcosis is not uncommon. Potential interpretation pitfalls should be kept in mind when fluorodeoxyglucose (FDG) positron emission tomography (PET) is used for differentiating pulmonary nodules and for discriminating infection from malignancy, especially in areas where the prevalence of granulomatous infection is high and in immunocompromised patients. In this case, a nodular mass was shown on chest radiography and computed tomographic (CT) scanning. A consolidated infection or a bronchioloalveolar carcinoma was suspected because the CT scan showed air bronchograms within the mass and another perihilar infiltration. The FDG PET scan clearly delineated the lesion and had intermediately high glucose uptake (standard uptake value, 3.8–4.0), which led to the exclusion of the possibility of bronchioloalveolar carcinoma because most of these tumors had normal or mildly increased FDG accumulation. Cryptococcoma was finally diagnosed. Hence, the CT scan and FDG PET played complementary roles in the differential diagnosis of this nodular mass.
Effects of formoterol and salmeterol on the production of Th1- and Th2-related chemokines by monocytes and bronchial epithelial cells
Authors: C-H. Hung, Y-T. Chu, Y-M. Hua, S-H. Hsu, C-S. Lin, H-C. Chang, M-S. Lee, Y-J. Jong
Journal: European Respiratory Journal (2008)

It is unknown whether formoterol and salmeterol, two long-acting beta(2)-adrenoreceptor agonists, have regulatory functions in the production of T-helper cell (Th) type 2- and Th1-related chemokines by monocytes and bronchial epithelial cells. In the present study, the effects of formoterol and salmeterol on lipopolysaccharide (LPS)-induced expression of the Th2-related chemokine macrophage-derived chemokine (MDC; CCL22) and the Th1-related chemokine interferon-gamma-inducible protein (IP)-10 (CXCL10) were investigated in a monocytic cell line, THP-1, and in human primary monocytes. In addition, their effects on the expression of the Th2-related chemokine thymus- and activation-regulated chemokine (TARC; CCL17) were evaluated in an epithelial cell line, BEAS-2B. Formoterol enhanced MDC but suppressed IP-10 production in monocytes induced by LPS. Higher doses of salmeterol were required to enhance LPS-induced MDC expression in THP-1 cells. Formoterol and salmeterol could significantly suppress TARC expression in BEAS-2B cells. These effects could be reversed by a selective beta(2)-adrenoreceptor antagonist, ICI-118551. Formoterol- and LPS-induced MDC expression was inhibited by budesonide. Both long-acting beta(2)-adrenoreceptor agonists suppressed thymus- and activation-regulated chemokine expression in bronchial epithelial cells mediated via beta(2)-adrenoreceptors. Formoterol at physiological concentrations could suppress lipopolysaccharide-induced T-helper cell type 1-related chemokine (interferon-gamma-inducible protein-10) but enhance T-helper cell type 2-related chemokine (macrophage-derived chemokine) expression in human monocytes. Long-acting beta(2)-adrenoreceptor agonists may increase T-helper cell type 2-related chemokine expression in monocytes and T-helper cell type 2 recruitment and, therefore, long-acting beta(2)-adrenoreceptor agonist monotherapy may not be an appropriate therapeutic option for asthma.
Cereal Fiber Improves Whole-Body Insulin Sensitivity in Overweight and Obese Women
Authors: Martin O. Weickert, Matthias Möhlig, Christof Schöfl, Ayman M. Arafat, Bärbel Otto, Hannah Viehoff, Corinna Koebnick, Angela Kohl, Joachim Spranger, Andreas F.H. Pfeiffer
Journal: Diabetes Care (2006)

OBJECTIVE—Cereal fiber intake is linked to reduced risk of type 2 diabetes in epidemiological observations. The pathogenic background of this phenomenon is unknown. Based on recent findings, we hypothesized that intake of purified insoluble oat fiber may improve whole-body insulin sensitivity. RESEARCH DESIGN AND METHODS—A randomized, controlled, single-blind, cross-over study was performed, and 17 overweight or obese subjects with normal glucose metabolism were analyzed. After consumption of nine macronutrient-matched portions of fiber-enriched bread (white bread enriched with 31.2 g insoluble fiber/day) or control (white bread) over a time period of 72 h, whole-body insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp. Energy intake was individually adjusted by providing standardized liquid meals. Hydrogen breath tests were performed to control for dietary adherence. RESULTS—When analyzing the entire cohort, whole-body glucose disposal was improved after fiber consumption (M value 6.56 ± 0.32 vs. 6.07 ± 0.27 mg · min−1 · kg−1; P = 0.043). Thirteen subjects had increased hydrogen breath test concentrations after fiber consumption, indicating probable dietary adherence. Restricting analysis to these subjects, improvements in M value (6.85 ± 0.34 vs. 6.06 ± 0.32 mg · min−1 · kg−1; P = 0.003) and insulin sensitivity, expressed as M/I ratio (M value divided by mean serum insulin at steady state: 3.73 ± 0.23 vs. 3.21 ± 0.27; P = 0.02), after fiber consumption were more pronounced. Plasma lipids, serum magnesium, ghrelin, and adiponectin concentrations, as well as substrate utilization and body weight, were not significantly changed by fiber intake (P &amp;gt; 0.15). CONCLUSIONS—Increased insoluble dietary fiber intake for 3 days significantly improved whole-body insulin sensitivity. These data suggest a potential mechanism linking cereal fiber intake and reduced risk of type 2 diabetes.
PC Cell–Derived Growth Factor Confers Resistance to Dexamethasone and Promotes Tumorigenesis in Human Multiple Myeloma
Authors: Wengang Wang, Jun Hayashi, Ginette Serrero
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We have shown previously that the 88 kDa glycoprotein PC cell–derived growth factor (PCDGF/GP88) is expressed and acts as an autocrine growth factor in human multiple myeloma cells. The present study investigates whether PCDGF/GP88 expression in multiple myeloma cells leads to the development of resistance to dexamethasone, a conventional drug for multiple myeloma patients. Experimental Design: PCDGF functions and signaling pathways in dexamethasone-induced apoptosis were studied using a representative dexamethasone-sensitive multiple myeloma cell line ARP-1. The effect of PCDGF/GP88 was further confirmed in PCDGF/GP88–overexpressed ARP-1 cells. Results: Dexamethasone inhibits cell growth and induces apoptosis in a time- and dose-dependent fashion. Exogenous addition of PCDGF/GP88 to the ARP-1 cells prevented dexamethasone-induced apoptosis as examined by flow cytometry analysis and poly(ADP-ribose)polymerase cleavage assay. Signaling studies showed that mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and nuclear factor-κB were involved in the antiapoptotic effect of PCDGF/GP88. Overexpression of PCDGF/GP88 in ARP-1 cells rendered the cells refractory to dexamethasone-mediated apoptosis, enhanced their ability to form colonies in soft agar, and to form tumors in vivo without any change in glucocorticoid receptor expression and function. Conclusion: These data suggest that expression of PCDGF/GP88 confers resistance to dexamethasone and increase tumorigenesis of multiple myeloma cells in mouse xenografts. Our data here also raises the possibility of PCDGF/GP88 as a potential therapeutic target for dexamethasone-resistant multiple myeloma.
Identification of Multiple Mechanisms of Resistance to Vemurafenib in a Patient with BRAFV600E-Mutated Cutaneous Melanoma Successfully Rechallenged after Progression
Authors: Emanuela Romano, Sylvain Pradervand, Alexandra Paillusson, Johann Weber, Keith Harshman, Katja Muehlethaler, Daniel Speiser, Solange Peters, Donata Rimoldi, Olivier Michielin
Journal: Clinical Cancer Research (2013)

To investigate the mechanism(s) of resistance to the RAF-inhibitor vemurafenib, we conducted a comprehensive analysis of the genetic alterations occurring in metastatic lesions from a patient with a BRAF(V600E)-mutant cutaneous melanoma who, after a first response, underwent subsequent rechallenge with this drug.We obtained blood and tissue samples from a patient diagnosed with a BRAF(V600E)-mutant cutaneous melanoma that was treated with vemurafenib and achieved a near-complete response. At progression, he received additional lines of chemo/immunotherapy and was successfully rechallenged with vemurafenib. Exome and RNA sequencing were conducted on a pretreatment tumor and two subcutaneous resistant metastases, one that was present at baseline and previously responded to vemurafenib (PV1) and one that occurred de novo after reintroduction of the drug (PV2). A culture established from PV1 was also analyzed.We identified two NRAS-activating somatic mutations, Q61R and Q61K, affecting two main subpopulations in the metastasis PV1 and a BRAF alternative splicing, involving exons 4-10, in the metastasis PV2. These alterations, known to confer resistance to RAF inhibitors, were tumor-specific, mutually exclusive, and were not detected in pretreatment tumor samples. In addition, the oncogenic PIK3CA(H1047R) mutation was detected in a subpopulation of PV1, but this mutation did not seem to play a major role in vemurafenib resistance in this metastasis.This work describes the coexistence within the same patient of different molecular mechanisms of resistance to vemurafenib affecting different metastatic sites. These findings have direct implications for the clinical management of BRAF-mutant melanoma.
Multiparameter Evaluation of the Expression In Situ of Normal and Tumor-Associated Antigens in Human Colorectal Carcinoma&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: C S Ernst, J W Shen, S Litwin, M Herlyn, H Koprowski, H F Sears
Journal: JNCI Journal of the National Cancer Institute (1986)

The immunoreactivity of a panel of monoclonal antibodies (MoAb) was studied in a series of patients with colorectal carcinomas to test the association of antigen expression with other parameters such as histopathologic stage, differentiation, and clinical outcome. Low-level binding to normal tissue and high-level binding to malignant tissue were observed with MoAb defining, respectively, a gastrointestinal cancer antigen (GICA), Leb (distal colon only), A, H type 2 antigen, X-like antigen, and the 200-kilodalton (Kd) protein of carcinoembryonic antigen (CEA). The degree of histologic differentiation correlated with the expression of Lea antigen, A, and Y haptens, whereas a progressive loss of these antigens coincided with loss of differentiation. Two undifferentiated carcinomas expressed only two, H type 2 antigen and a highly glycosylated protein of 20-50 Kd, of the 14 antigens investigated. An interesting, but not significant, association between Leb antigen expression and more extensive disease was found: Whereas 71% of Dukes C tumors were positive for Leb, only 48% of patients with Dukes A and B2 tumors showed the presence of Leb antigen. On the other hand, the presence of B72.3-defined antigen is significantly associated with an earlier stage of disease. Chi-square tests to assess the association of antigen positivity with disease recurrence indicated a significant binding association with tumor recurrence over a broad range of percent positive cells for two MoAb defining different determinants of GICA. Similar associations, but over a narrow range of positive cells, were found for H type 2 antigen and the 200-Kd protein of CEA.