tbuckley/cabot-search huggingface dataset:
Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Pharmacodynamic Measure of Response After Acute Dosing of AG-013736, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors: Results From a Phase I Study
Authors: Glenn Liu, Hope S. Rugo, George Wilding, Teresa M. McShane, Jeffrey L. Evelhoch, Chaan Ng, Edward Jackson, Frederick Kelcz, Benjamin M. Yeh, Fred T. Lee, Chusilp Charnsangavej, John W. Park, Edward A. Ashton, Heidi M. Steinfeldt, Yazdi K. Pithavala, Steven D. Reich, Roy S. Herbst
Journal: Journal of Clinical Oncology (2005)

Purpose Identifying suitable markers of biologic activity is important when assessing novel compounds such as angiogenesis inhibitors to optimize the dose and schedule of therapy. Here we present the pharmacodynamic response to acute dosing of AG-013736 measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Patients and Methods Thirty-six patients with advanced solid tumors were treated with various doses of AG-013736. In addition to standard measures of objective disease response and pharmacokinetic analysis, DCE-MRI scans were acquired at baseline and repeated at cycle 1—day 2 after the scheduled morning dose of the AG-013736 in 26 patients. Indicators of a vascular response, such as the volume transfer constant (K trans ) and initial area under the curve (IAUC), were calculated to assess the effect of treatment on tumor vascular function. Results Evaluable vascular response data were obtained in 17 (65%) of 26 patients. A linear correlation was found in which the percentage change from baseline to day 2 in K trans and IAUC was inversely proportional to AG-013736 exposure. Using a conservative a priori assumption that a ≥ 50% decrease in K trans was indicative of an objective vascular response, a 50% decrease in K trans was achieved and corresponded to a plasma AUC 0-24 of &gt; 200 ng · h/mL. Conclusion A sufficient decrease in tumor vascular parameters was observed at a dose chosen for additional phase II testing by conventional toxicity criteria. In addition, the day 2 vascular response measured using DCE-MRI seems to be a useful indicator of drug pharmacology, and additional research is needed to determine if it is a suitable marker for predicting clinical activity.
An unsuitable and degraded diet? Part two: realities of the mid-Victorian diet
Authors: Paul Clayton, Judith Rowbotham
Journal: Journal of the Royal Society of Medicine (2008)

Principal findings
In this article we use a multiplicity of sources to document food availability in the period 1850–1900 and cross-reference this against earnings data to create a qualitative overview of the mid-Victorian diet, backed up by quantitative data where available and credible. Our findings reveal that in contrast to received wisdom, working-class mid-Victorians ate a superior version of the Mediterranean diet, with a much higher consumption of vegetables and fruits than has hitherto been realized. The positive impact of this diet on mid-Victorian health is described in the last article in this series, as are the implications for public health policy and research today.
Confidence intervals rather than P values: estimation rather than hypothesis testing.
Authors: M J Gardner, D G Altman
Journal: BMJ (1986)

Overemphasis on hypothesis testing--and the use of P values to dichotomise significant or non-significant results--has detracted from more useful approaches to interpreting study results, such as estimation and confidence intervals. In medical studies investigators are usually interested in determining the size of difference of a measured outcome between groups, rather than a simple indication of whether or not it is statistically significant. Confidence intervals present a range of values, on the basis of the sample data, in which the population value for such a difference may lie. Some methods of calculating confidence intervals for means and differences between means are given, with similar information for proportions. The paper also gives suggestions for graphical display. Confidence intervals, if appropriate to the type of study, should be used for major findings in both the main text of a paper and its abstract.
Genetic Profiling of Epithelial Cells Expressing E-Cadherin Repressors Reveals a Distinct Role for Snail, Slug, and E47 Factors in Epithelial-Mesenchymal Transition
Authors: Gema Moreno-Bueno, Eva Cubillo, David Sarrió, Héctor Peinado, Socorro María Rodríguez-Pinilla, Sonia Villa, Victoria Bolós, Mireia Jordá, Angels Fabra, Francisco Portillo, José Palacios, Amparo Cano
Journal: Cancer Research (2006)

Abstract The transcription factors Snail, Slug, and bHLH E47 have been recently described as direct repressors of E-cadherin and inducers of epithelial-mesenchymal transition (EMT) and invasion when overexpressed in epithelial cells. Although a role of those factors in tumor progression and invasion has been proposed, whether the different repressors play distinct or redundant roles in the tumorigenic process has not been established. To further investigate this important issue, we have analyzed the gene expression profiling of Madin-Darby canine kidney (MDCK) epithelial cells expressing the different repressors (MDCK-Snail, MDCK-Slug, and MDCK-E47 cells) versus control MDCK cells by cDNA microarrays. A total of 243 clones (228 genes and 15 expressed sequence tags) were found to be differentially expressed between either of the three MDCK-derived cell lines and control MDCK cells. Twenty two of the candidate genes were validated by Northern blot, Western blot, immunofluorescence, and promoter analyses in cell lines and by immunohistochemistry in xenografted tumors. Gene clustering analysis indicated that about a third of the 243 candidate genes were common to MDCK cells expressing Snail, Slug, or E47 factors, whereas the rest of the genes were regulated in only one or two cell types. Differentially regulated genes include those related to EMT (45 genes), transcriptional regulation (18 genes), cell proliferation and signaling (54 genes), apoptosis (12 genes), and angiogenesis (9 genes). These results indicate that Snail, Slug, and E47 transcription factors induce common and specific genetic programs, supporting a differential role of the factors in tumor progression and invasion. (Cancer Res 2006; 66(19): 9543-56)
Yeast-Derived β-Glucan Augments the Therapeutic Efficacy Mediated by Anti–Vascular Endothelial Growth Factor Monoclonal Antibody in Human Carcinoma Xenograft Models
Authors: Carolina Salvador, Bing Li, Richard Hansen, Daniel E. Cramer, Maiying Kong, Jun Yan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Bevacizumab is a recombinant IgG1 humanized monoclonal antibody against vascular endothelial growth factor (VEGF). Its proposed mechanism of action is independent of immune effector functions. Many human carcinomas not only secrete VEGF but also express membrane-bound VEGF. In addition, VEGF receptors are expressed on tumor cells. It is hypothesized that bevacizumab could bind membrane-bound VEGF or VEGF-VEGF receptor complexes on tumors, thereby initiating potential immunologic consequences. We previously showed that yeast-derived β-glucan functions with antitumor antibodies that activate complement to recruit complement receptor 3–expressing leukocytes capable of mediating complement receptor 3–dependent cellular cytotoxicity of tumors opsonized with iC3b. In the current study, the therapeutic efficacy mediated by combining bevacizumab with yeast-derived β-glucan was studied in human carcinoma xenograft models. Experimental Design: Human tumor cell lines were screened for membrane-bound VEGF expression both in vitro and in vivo. Complement activation mediated by bevacizumab was examined. Tumor cell lines positive or negative for membrane-bound VEGF expression were implanted in severe combined immunodeficient mice to establish xenograft models. Tumor-bearing mice were treated with different regimens. Tumor regression and long-term survival were recorded. Results: Human ovarian carcinoma SKOV-3 cells expressed membrane-bound VEGF both in vitro and in vivo. Bevacizumab was bound to membrane-bound VEGF, activated complement, and synergized with β-glucan to elicit cellular cytotoxicity in vitro. In vivo study showed that β-glucan could significantly augment the therapeutic efficacy mediated by bevacizumab. Conclusions: Yeast-derived β-glucan can synergize with anti-VEGF monoclonal antibody bevacizumab for the treatment of cancer with membrane-bound VEGF expression.
Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism.
Authors: A Consoli, N Nurjhan, J J Reilly, D M Bier, J E Gerich
Journal: Journal of Clinical Investigation (1990)

To assess the mechanisms responsible for increased gluconeogenesis in noninsulin-dependent diabetes mellitus (NIDDM), we infused [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose in 10 postabsorptive NIDDM subjects and in 9 age- and weight-matched nondiabetic volunteers and measured systemic appearance of alanine and lactate, their release from forearm tissues, and their conversion into plasma glucose (corrected for Krebs cycle carbon exchange). Systemic appearance of lactate and alanine were both significantly greater in diabetic subjects (18.2 +/- 0.9 and 5.8 +/- 0.4 mumol/kg/min, respectively) than in the nondiabetic volunteers (12.6 +/- 0.7 and 4.2 +/- 0.3 mumol/kg/min, respectively, P less than 0.001 and P less than 0.01). Conversions of lactate and alanine to glucose were also both significantly greater in NIDDM subjects (8.6 +/- 0.5 and 2.4 +/- 0.1 mumole/kg/min, respectively) than in nondiabetic volunteers (4.2 +/- 0.4 and 1.8 +/- 0.1 mumol/kg/min, respectively, P less than 0.001 and P less than 0.025). The proportion of systemic alanine appearance converted to glucose was not increased in NIDDM subjects (42.7 +/- 1.9 vs. 44.2 +/- 2.9% in nondiabetic volunteers), whereas the proportion of systemic lactate appearance converted to glucose was increased in NIDDM subjects (48.3 +/- 3.8 vs. 34.2 +/- 3.8% in nondiabetic volunteers, P less than 0.025); the latter increased hepatic efficiency accounted for approximately 40% of the increased lactate conversion to glucose. Neither forearm nor total body muscle lactate and alanine release was significantly different in NIDDM and nondiabetic volunteers. Therefore, we conclude that increased substrate delivery to the liver and increased efficiency of intrahepatic substrate conversion to glucose are both important factors for the increased gluconeogenesis of NIDDM and that tissues other than muscle are responsible for the increased delivery of gluconeogenic precursors to the liver.
Interferon gamma and lipopolysaccharide promote macrophage adherence to basement membrane glycoproteins.
Authors: L M Shaw, A M Mercurio
Journal: The Journal of Experimental Medicine (1989)

The ability of thioglycollate (TG)-elicited peritoneal macrophages, a population of recently recruited monocytes, to adhere to the basement membrane glycoproteins laminin and type IV collagen is not a constitutive function of these cells. Adherence can be induced, however, by treatment with IFN-gamma and LPS. In general, IFN-gamma is more potent than LPS in promoting this adherence. Maximal adherence, however, is observed when IFN-gamma (greater than or equal to 5 U/ml) is used together with LPS (2.0 ng/ml). These requirements parallel the conditions needed to obtain tumoricidal activation of TG-elicited macrophages. Adherence to laminin, in the presence of these stimuli, is transient, being maximal at 8 h after their addition and diminishing with longer periods of incubation. In contrast, adherence to type IV collagen does not appear to be transient and IFN-gamma and LPS induce a more prolonged association of macrophages with this substratum.
Combined Angioplasty and Pharmacological Intervention Versus Thrombolysis Alone in Acute Myocardial Infarction (CAPITAL AMI Study)
Authors: Michel R. Le May, George A. Wells, Marino Labinaz, Richard F. Davies, Michele Turek, Danielle Leddy, Justin Maloney, Tim McKibbin, Brendan Quinn, Rob S. Beanlands, Chris Glover, Jean-François Marquis, Edward R. O’Brien, William L. Williams, Lyall A. Higginson
Journal: Journal of the American College of Cardiology (2005)
Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon-α
Authors: Hideki Hagiwara, Norio Hayashi, Eiji Mita, Keiji Ueda, Tetsuo Takehara, Akinori Kasahara, Hideyuki Fusamoto, Takenobu Kamada
Journal: Hepatology (1992)

We tested serial serum samples for hepatitis C virus RNA from patients undergoing treatment for chronic hepatitis C with interferon-α using an assay that combined reverse transcription and polymerase chain reaction. The subjects studied were 20 patients with chronic hepatitis who had serum antibody to hepatitis C virus (anti-C100-3). Before therapy, hepatitis C virus RNA was detected in 18 (90%) and 20 (100%) patients using primer sets derived from the NS3 region or the 5′-noncoding region of hepatitis C virus, respectively. Hepatitis C virus RNA became undetectable in all patients whose ALT level fell into the normal range during therapy. However, hepatitis C virus RNA reappeared in all patients whose ALT levels rose again after therapy, usually before the relapse. In patients whose ALT levels did not become normal, hepatitis C virus RNA did not disappear during therapy. Thus therapy with interferon-α appears to be beneficial in chronic hepatitis C because of its suppressive effects on hepatitis C virus replication. Detection of hepatitis C virus RNA in serum is useful for evaluating the antiviral effect of interferon (Hepatology 1992;15:37-41).
Cardiorespiratory responses to incremental exercise in patients with pulmonary Langerhans' cell histiocytosis
Authors: Camille Rolland-Debord, Stephanie Fry, Carole Langlois, Bernard Aguilaniu, Agnes Bellocq, Stephane Dominique, Alain Delobbe, Geraldine François, Kana Yasunaga, Abdellatif Tazi, Benoit Wallaert
Journal: European Respiratory Journal (2014)

Pulmonary Langerhans9 cell histiocytosis (PLCH) is an uncommon diffuse lung disease occurring in smokers9young adults characterized by a reduced diffusing capacity of the lung for carbon monoxide (DLCO).The aim of the study was to analyze the determinants of exercise impairment in a cohort of adult patients affected by PLCH, and compared with pulmonary function at rest and with HRCT findings. Cardiopulmonary exercise testing with arterial blood sample was carried out in 62 patients (27/62 men) with a mean age at diagnosis of 33±10 years, and a history of cigarette use (60/62). A limitation of aerobic capacity (VO2peak
Hydrocortisone Ointment in the Eczemas
Authors: R. Church
Journal: BMJ (1955)

Those interested in reducing the appalling number of deaths on the road might do well to press for a radical revision of the present system of granting driving licences to pro- fessional drivers. SummayCivilian medical board records of 1,276 professional drivers were examined for causes of rejection from military service.Physical defects and impairment of vision found were considered in relation to the declar- ation of physical fitness made on the application form for a driving licence.
Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels
Authors: M. Colleoni, A. Rocca, M.T. Sandri, L. Zorzino, G. Masci, F. Nolè, G. Peruzzotti, C. Robertson, L. Orlando, S. Cinieri, F. de Braud, G. Viale, A. Goldhirsch
Journal: Annals of Oncology (2002)
THE INFLUENCE OF CORTISONE-ACETATE ON SOME SERUM PHOSPHORUS METABOLITES IN YOUNG MALE SCHIZOPHRENICS
Authors: PAUL KOCH, CAMILLE LAURIN, ROGER LEMIEUX
Journal: American Journal of Psychiatry (1961)

Oral cortisone acetate can differentiate between young male schizophrenics and a comparable control group by inducing an increase in alkaline phosphatases and a decrease in phospho-lipids in the former. No such changes were observed in the latter group.
Radioimmunassay for measurement of triiodothyronine in human serum
Authors: Inder J. Chopra, David H. Solomon, Gildon N. Beall
Journal: Journal of Clinical Investigation (1971)

A convenient, specific, precise, and reproducible radioimmunoassay system for measurement of triiodothyronine (T(3)) in human serum has been developed. The procedure compares the ability of standards and unknowns to compete with radioactive T(3) for binding sites on a T(3)-binding antiserum produced in rabbits by immunization with human thyroglobulin. The assay is set up in the presence of 250 ng thyroxine (T(4)) in all tubes, to mobilize T(3) from its binding with the thyronine-binding globulin (TBG), and athyreotic sheep serum in standards to correct for the TBG in the unknowns. The method regularly detected 0.4 ng T(3), which would correspond to a T(3) concentration of 100 ng/100 ml when 400 mul of serum is analyzed. The mean recovery of unlabeled T(3) added to normal serum pools was 106%. Serial dilution of hyperthyroid sera containing high concentrations of T(3) with athyreotic sheep serum yielded expected values. The serum T(3) concentration in 80% of 31 euthyroid normal subjects was less than 100 ng/100 ml (range < 100-170 ng/100 ml); it was greater than 170 ng/100 ml in 89% of 27 sera of hyperthyroid patients with untreated Graves' disease (range < 100-1300, mean 519 in 25 sera with detectable T(3)). The concentration of serum T(3) fell, frequently to undetectable levels, during treatment of hyperthyroid patients with antithyroid drugs. The serum T(3) concentration in four hypothyroid patients was less than 100 ng/100 ml.
Effect of continuous and bilevel noninvasive ventilation for acute asthma exacerbation - A randomized controlled trial
Authors: Silmara Guanaes Hanekom, Heleen van Aswegen, Louise Engelbrecht, Piet J. Becker
Journal: European Respiratory Journal (2012)

Guidelines for management of acute asthma exacerbation (AAE) centre on pharmacological interventions and invasive mechanical ventilation. The role of non-invasive positive pressure ventilation (NPPV) in AAE remains unanswered.  Aims:  We hypothesized that adding continuous positive airway pressure (CPAP) or bilevel positive pressure ventilation (BPPV) to standard therapy (ST) would improve lung function and clinical signs faster than ST alone.  Methods:  Thirty patients with severe AAE [peak expiratory flow rate percentage (PEFR%) predicted  Results:  Groups presented similar baseline characteristics. Mean baseline PEFR% predicted was 35.2 (10.7) % [ST], 30.5 (11.7) % [CPAP] and 33.5 (13.8) % [BPPV]. PEFR significantly improved in the CPAP group from the first 30 minutes of treatment (PEFR  p  = 0.00; PEFR% predicted  p  = 0.00) compared to the BPPV and ST groups. Improvement in respiratory rate (RR) ( p  = 0.05) and sensation of breathlessness (SB) ( p  = 0.00) was significantly better in the BPPV group from the first 30 minutes.  Discussion:  The significant improvement in PEFR in the CPAP group could be related to its intrinsic effect on the airway smooth muscle and/or its load. The positive effect of BPPV on RR and SB could be related to the inspiratory assistance provided.  Conclusion:  The addition NPPV to ST in acute severe asthma exacerbation, improved lung function and clinical signs faster than ST, yet CPAP was faster and more effective in reducing bronchospasm than BPPV.
Msh2 ATPase Activity Is Essential for Somatic Hypermutation at A-T Basepairs and for Efficient Class Switch Recombination
Authors: Alberto Martin, Ziqiang Li, Diana P. Lin, Philip D. Bardwell, Maria D. Iglesias-Ussel, Winfried Edelmann, Matthew D. Scharff
Journal: The Journal of Experimental Medicine (2003)

Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytidine deaminase–mediated cytidine deamination of immunoglobulin genes. MutS homologue (Msh) 2−/− mice have reduced A-T mutations and CSR. This suggests that Msh2 may play a role in repairing activation-induced cytidine deaminase–generated G-U mismatches. However, because Msh2 not only initiates mismatch repair but also has other functions, such as signaling for apoptosis, it is not known which activity of Msh2 is responsible for the effects observed, and consequently, many models have been proposed. To further dissect the role of Msh2 in SHM and CSR, mice with a “knockin” mutation in the Msh2 gene that inactivates the adenosine triphosphatase domain were examined. This mutation (i.e., Msh2G674A), which does not affect apoptosis signaling, allows mismatches to be recognized but prevents Msh2 from initiating mismatch repair. Here, we show that, similar to Msh2−/− mice, SHM in Msh2G674A mice is biased toward G-C mutations. However, CSR is partially reduced, and switch junctions are more similar to those of postmeiotic segregation 2−/− mice than to Msh2−/− mice. These results indicate that Msh2 adenosine triphosphatase activity is required for A-T mutations, and suggest that Msh2 has more than one role in CSR.
CD200 in CNS tumor-induced immunosuppression: the role for CD200 pathway blockade in targeted immunotherapy
Authors: Christopher L Moertel, Junzhe Xia, Rebecca LaRue, Nate N Waldron, Brian M Andersen, Robert M Prins, Hideho Okada, Andrew M Donson, Nicholas K Foreman, Matthew A Hunt, Christopher A Pennell, Michael R Olin
Journal: Journal for ImmunoTherapy of Cancer (2014)

Immunological quiescence in the central nervous system (CNS) is a potential barrier to immune mediated anti-tumor response. One suppressive mechanism results from the interaction of parenchyma-derived CD200 and its receptor on myeloid cells. We suggest that CD200/CD200R interactions on myeloid cells expand the myeloid-derived suppressor cell (MDSC) population and that blocking tumor-derived CD200 will enhance the efficacy of immunotherapy.CD200 mRNA expression levels in human brain tumor tissue samples were measured by microarray. The amount of circulating CD200 protein in the sera of patients with brain tumors was determined by ELISA and, when corresponding peripheral blood samples were available, was correlated quantitatively with MDSCs. CD200-derived peptides were used as competitive inhibitors in a mouse model of glioblastoma immunotherapy.CD200 mRNA levels were measured in human brain tumors, with different expression levels being noted among the sub groups of glioblastoma, medulloblastoma and ependymoma. Serum CD200 concentrations were highest in patients with glioblastoma and correlated significantly with MDSC expansion. Similarly, in vitro studies determined that GL261 cells significantly expanded a MDSC population. Interestingly, a CD200R antagonist inhibited the expansion of murine MDSCs in vitro and in vivo. Moreover, inclusion of CD200R antagonist peptide in glioma tumor lysate-derived vaccines slowed tumor growth and significantly enhanced survival.These data suggest that CNS-derived tumors can evade immune surveillance by engaging CD200. Because of the homology between mouse and human CD200, our data also suggest that blockade of CD200 binding to its receptor will enhance the efficacy of immune mediated anti-tumor strategies for brain tumors.
CHEMICAL INVESTIGATIONS ON THE ACTIVE PRINCIPLES OF THE PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES
Authors: S. A. Morell, Gregory Shwartzman
Journal: The Journal of Experimental Medicine (1938)

B. coli, meningococcus, and B. typhosus have been cultivated in a diffused broth medium, prepared by immersing cellophane bags containing saline into nutrient broth. An abundant growth occurred inside the bags, while the outside broth remained sterile. Under these conditions, the production of the active principles of the phenomenon of local skin reactivity to bacterial filtrates has been consistent. When the culture filtrates so obtained were redialyzed against saline, active preparations were obtained which were practically free from non-specific ingredients.