tbuckley/cabot-search huggingface dataset:
Phase II Study of Capecitabine, Oxaliplatin, and Erlotinib in Previously Treated Patients With Metastastic Colorectal Cancer
Authors: Jeffrey A. Meyerhardt, Andrew X. Zhu, Peter C. Enzinger, David P. Ryan, Jeffrey W. Clark, Matthew H. Kulke, Craig C. Earle, Michele Vincitore, Ann Michelini, Susan Sheehan, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2006)

To investigate the combination of erlotinib, capecitabine, and oxaliplatin in patients who were previously treated for metastatic colorectal cancer.Patients were eligible if they had metastatic colorectal cancer that progressed, were intolerant to first-line chemotherapy, or had disease recurrence within 1 year of adjuvant therapy for early-stage disease. Each 21-day cycle consisted of daily oral erlotinib at 150 mg, oral capecitabine at 1,000 mg/m2 (reduced to 750 mg/m2 after the first 13 patients) twice a day on days 1 to 14, and intravenous oxaliplatin at 130 mg/m2 on day 1.Thirty-two patients were enrolled onto this phase II study. By intention-to-treat analyses, eight patients (25%) experienced a partial response and 14 patients (44%) had stable disease for at least 12 weeks. The median progression-free survival was 5.4 months and the median overall survival was 14.7 months. These results were essentially unchanged when limited to the cohort of patients (78%) who received prior irinotecan for metastatic colorectal cancer. Most common grade 3 to 4 toxicities included diarrhea (38%), nausea/emesis (19%), fatigue (16%), dehydration (16%), and dermatitis (13%); grade 3 or 4 toxicities were reduced with a lower starting dose of capecitabine.The combination of capecitabine, oxaliplatin, and erlotinib seems to have promising activity against metastatic colorectal cancer in patients who received prior chemotherapy, with a relatively higher response rate and progression-free survival compared with previous reports of either infusional FU, leucovorin, and oxaliplatin or capecitabine and oxaliplatin in similar patient populations.
Direct-Acting Antiviral Agents for Hepatitis C Virus Infection
Authors: Jennifer J. Kiser, Charles Flexner
Journal: The Annual Review of Pharmacology and Toxicology (2012)

Two selective inhibitors of the hepatitis C virus (HCV) protease nearly double the cure rates for this infection when combined with peginterferon alfa and ribavirin. These drugs, boceprevir and telaprevir, received regulatory approval in 2011 and are the first direct-acting antiviral agents (DAAs) that selectively target HCV. During 2012, at least 30 additional DAAs were in various stages of clinical development. HCV protease inhibitors, polymerase inhibitors, and NS5A inhibitors (among others) can achieve high cure rates when combined with peginterferon alfa and ribavirin and demonstrate promise when used in combination with one another. Current research is attempting to improve the pharmacokinetics and tolerability of these agents, define the best regimens, and determine treatment strategies that produce the best outcomes. Several DAAs will reach the market simultaneously, and resources will be needed to guide the use of these drugs. We review the clinical pharmacology, trial results, and remaining challenges of DAAs for the treatment of HCV.
Noninvasive Targeted Imaging of Matrix Metalloproteinase Activation in a Murine Model of Postinfarction Remodeling
Authors: Haili Su, Francis G. Spinale, Lawrence W. Dobrucki, James Song, Jing Hua, Sarah Sweterlitsch, Donald P. Dione, Patti Cavaliere, Conroy Chow, Brian N. Bourke, Xiao-Yu Hu, Michael Azure, Padmaja Yalamanchili, Richard Liu, Edward H. Cheesman, Simon Robinson, D. Scott Edwards, Albert J. Sinusas
Journal: Circulation (2005)

Background— Time-dependent activation of matrix metalloproteinases (MMPs) after myocardial infarction (MI) contributes to adverse left ventricular (LV) remodeling; however, noninvasive methods to monitor this process serially are needed. Methods and Results— MMP-targeted radiotracers were developed that displayed selective binding kinetics to the active MMP catalytic domain. Initial nonimaging studies were performed with a 111 In-labeled MMP-targeted radiotracer ( 111 In-RP782) and negative control compound ( 111 In-RP788) in control mice (Ctrl) and in mice 1 week after surgically induced MI. Localization of 111 In-RP782 was demonstrated within the MI by microautoradiography. A 334±44% increase ( P &lt;0.001 versus Ctrl) in relative retention of 111 In-RP782 was confirmed by gamma well counting of myocardium. Subsequent high-resolution dual-isotope planar and hybrid micro–single-photon emission computed tomography/CT imaging studies with an analogous 99m Tc-labeled MMP-targeted radiotracer ( 99m Tc-RP805) and 201 Tl demonstrated favorable biodistribution and clearance kinetics of 99m Tc-RP805 for in vivo cardiac imaging, with robust retention 1 to 3 weeks after MI in regions of decreased 201 Tl perfusion. Gamma well counting yielded a similar ≈300% increase in relative myocardial retention of 99m Tc-RP805 in MI regions (Ctrl, 102±9%; 1 week, 351±77%; 2 weeks, 291±45%; 3 weeks, 292±41%; P &lt;0.05 versus Ctrl). Myocardial uptake in the MI region was also significantly increased ≈5-fold when expressed as percentage injected dose per gram tissue. There was also a significant 2-fold increase in myocardial activity in remote regions relative to control mice, suggesting activation of MMPs in regions remote from the MI. Conclusions— This novel noninvasive targeted MMP radiotracer imaging approach holds significant diagnostic potential for in vivo localization of MMP activation and tracking of MMP-mediated post-MI remodeling.
(38) Sézary syndrome
Authors: R.C.D. Staughton, P.D. Samman, D.E. Sharvill
Journal: British Journal of Dermatology (2006)

Journal Article (38) Sézary syndrome Get access R.C.D. Staughton, R.C.D. Staughton Westminster Hospital, London Search for other works by this author on: Oxford Academic Google Scholar P.D. Samman, P.D. Samman Westminster Hospital, London Search for other works by this author on: Oxford Academic Google Scholar D.E. Sharvill D.E. Sharvill Westminster Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue s14, 1 December 1976, Pages 75–76, https://doi.org/10.1111/j.1365-2133.1976.tb07926.x Published: 01 December 1976
<i>ABL</i> oncogene amplification with <i>p16</i><sup><i>INK4a</i></sup> gene deletion in precursor T‐cell acute lymphoblastic leukemia/lymphoma: Report of the first case
Authors: Hee‐Jin Kim, Hee‐Yeon Woo, Hong‐Hoe Koo, Eun‐Young Tak, Sun‐Hee Kim
Journal: American Journal of Hematology (2004)

Abstract Gene amplification is a relatively rare event in hematologic malignancies. The ABL gene on chromosome band 9q34 is a proto‐oncogene and is the well‐known translocation partner of the BCR gene on 22q11 giving rise to t(9;22)(q34;q11), which is the hallmark of chronic myeloid leukemia and is the most common chromosomal abnormality in adult acute lymphoblastic leukemia (ALL). Amplification of ABL is an exceedingly rare event, with only less than 5 cases reported in the literature. The p16 INK4a (or CDKN2A ) gene on 9p21 is a tumor suppressor gene, and deletion thereof is recently recognized as one of the most common genetic abnormalities in ALL. The authors herein describe an 8‐year‐old male patient with precursor T‐cell ALL harboring both ABL gene amplification and p16 INK4a gene deletion. Fluorescence in situ hybridization (FISH) analysis using BCR / ABL probes revealed five or more ABL signals, indicating amplification in 51.5% of interphase nuclei. FISH using p16 INK4a gene probes showed heterozygous p16 INK4a deletion in 71.0%. On conventional cytogenetic analysis, however, only 10 metaphases were available, which showed the normal karyotype, 46,XY[10], serving no evidence for the findings on FISH. This is the first report of an ALL case with ABL amplification, and the authors speculate that both ABL proto‐oncogene amplification and the p16 INK4a tumor suppressor gene deletion have been implicated in leukemogenesis in the present case, although whether the ABL amplification truly contributes to the leukemogenesis or merely an epiphenomenon representing underlying genomic instability remains to be determined. Am. J. Hematol. 76:360–363, 2004. © 2004 Wiley‐Liss, Inc.
Potassium in Dog Ventricular Muscle: Kinetic Studies of Distribution and Effects of Varying Frequency of Contraction and Potassium Concentration of Perfusate
Authors: G. A. Langer, A. J. Brady, S.D. Serena, S.T. Ton
Journal: Circulation Research (1966)

Four phases (0 to 3) were defined kinetically for potassium in the dog papillary muscle when perfused arterially for four to five hours with solution containing 4 mM/liter K + . Total tissue K + fell from 91.1±1.99 to 41.0±1.06 mmoles/liter after three hours perfusion. It then remained stable during the period when kinetic studies were done. The mean rate constant λ (min -1 ), potassium content (mmoles/liter tissue water) and suggested origin of each phase are respectively: (phase 0) λ 0 = 3.2, 0.3, vascular; (phase 1) λ 1 = 0.65, 2.06, interstitial; (phase 2) λ 2 = 0.0139, 39.3, intracellular; (phase 3) λ 3 &lt; 0.004, &lt;0.5, origin unknown. Alteration of K + concentration in perfusing fluid produced significant changes in the intracellular exchange rate of K + . This was in marked contrast to increments in frequency of contraction which had no effect on the overall exchangeability of intracellular potassium. Increases in rate, however, were associated with a transient net loss of intracellular K + . This loss continued if the active tension of the muscle declined and if contracture progressed. The loss ceased if muscle function remained stable during continued increased frequency of contraction. A positive tension staircase was approximately proportional to the net K + loss. The net K + loss was 0.93 mmole/liter tissue water in nine muscles in which a mean 27 beats/min rate increment was introduced for a mean of 16 minutes. This represented 2.4% of intracellular K + . A significant time lag was found before the net K + loss reached a maximum rate and began to decline. This is compared with the previously demonstrated transient net increment in Ca ++ uptake that accompanies increased frequency of contraction. These ionic movements are consistent with the theory that Na + movements in and out of a "specialized membrane region" are related to Ca ++ movements and thereby influence the control of myocardial contractility.
SELECTIVE ROLES OF THYMUS-DERIVED LYMPHOCYTES IN THE ANTIBODY RESPONSE
Authors: Tomio Tada, Toshitada Takemori
Journal: The Journal of Experimental Medicine (1974)

Passively transferred thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) exerted differential suppressive effect on IgM and IgG antibody responses of syngeneic recipients immunized with DNP-KLH depending primarily on the time when KLH-primed cells were transferred. This was demonstrated by the decrease in the numbers of DNP-specific direct and indirect PFC in the spleen of the recipients given KLH-primed cells at different times during primary and secondary immunization. Whereas the cell transfer simultaneously with or 2 days after the primary immunization produced only slight suppression of the peak IgM antibody response, it caused profound suppression of late IgM and IgG antibody responses. By contrast, the cell transfer 3 days after the immunization produced immediate suppression of the ongoing IgM antibody response resulting in its earlier termination, while being unable to prevent the induction of IgG antibody response. KLH-primed cells could moderately suppress the secondary anti-DNP antibody response, in which IgG antibody response was found to be slightly more sensitive than IgM antibody response to the suppressive influence of KLH-primed cells. The suppressive effect of the KLH-primed spleen cells was completely eliminated by the in vitro treatment of the cells with anti-theta and C before cell transfer, indicating that cells responsible for the suppression are, in fact, T cells. The suppression of DNP-specific antibody response by KLH-primed T cells was achieved only if the recipients were immunized with DNP-KLH but not with DNP-heterologous carrier, suggesting that direct interaction between T and B cells is necessary for the suppression of the antibody response. It is concluded that susceptibility of B cells to the specific suppressive influence of T cells is inherently different depending on the differentiation stage of B cells and on the immunoglobulin class they are destined to produce.
Tight Junctions in Epithelial Cells of Human Fetal Hindgut, Normal Colon, and Colon Adenocarcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Polak-Charcon, J Shoham, Y Ben-Shaul
Journal: JNCI Journal of the National Cancer Institute (1980)

Tight Junctions in Epithelial Cells of Human Fetal Hindgut, Normal Colon, and Colon Adenocarcinoma Get access Sylvie Polak-Charcon, Sylvie Polak-Charcon Search for other works by this author on: Oxford Academic PubMed Google Scholar Jacob Shoham, Jacob Shoham Search for other works by this author on: Oxford Academic PubMed Google Scholar Yehuda Ben-Shaul Yehuda Ben-Shaul Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 65, Issue 1, July 1980, Pages 53–62, https://doi.org/10.1093/jnci/65.1.53 Published: 01 July 1980 Article history Received: 31 August 1979 Accepted: 02 December 1979 Published: 01 July 1980
Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis
Authors: Jianhua Yao, Angelo M. Taveira-DaSilva, Amanda M. Jones, Patricia Julien-Williams, Mario Stylianou, Joel Moss
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis.To determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients.Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts were quantified with a computer-aided diagnosis system in 38 patients. Then we compared cyst scores from the last study on sirolimus with studies done on sirolimus therapy. In 12 patients, we evaluated rates of change in lung function and cyst scores off and on sirolimus.Sirolimus reduced yearly declines in FEV1 (-2.3 ± 0.1 vs. 1.0 ± 0.3% predicted; P < 0.001) and diffusing capacity of carbon monoxide (-2.6 ± 0.1 vs. 0.9 ± 0.2% predicted; P < 0.001). Cyst scores 1.2 ± 0.8 years (30.5 ± 11.9%) and 2.5 ± 2 years (29.7 ± 12.1%) after initiating sirolimus were not significantly different from pretreatment values (28.4 ± 12.5%). In 12 patients followed for 5 years, a significant reduction in rates of yearly decline in FEV1 (-1.4 ± 0.2 vs. 0.3 ± 0.4% predicted; P = 0.025) was observed. Analyses of 104 computed tomography scans showed a nonsignificant (P = 0.23) reduction in yearly rates of change of cyst scores (1.8 ± 0.2 vs. 0.3 ± 0.3%; P = 0.23) and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy.Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy.
The effects of tension on acetylstrophanthidin-induced transient depolarizations and aftercontractions in canine myocardial and Purkinje tissues.
Authors: G R Ferrier
Journal: Circulation Research (1976)

Transmembrane potentials and contractile activity were recorded from isolated canine Purkinje and ventricular muscle preparations exposed to acetylstrophantidin (AS) and subjected to a resting tension equal to 80% of that required to elicit peak developed tension. AS induced transient depolarizations (TD's) accompanied by aftercontractions in Purkinje tissue. AS also induced aftercontractions in 11 muscle preparations, and in seven of these the mechanical events were associated with TD's. Aftercontractions and TD's in both and the coupling intervals were directly related to the preceding basic cycle length (BCL). The amplitudes of aftercontractions and TD's reached a maximum at a coupling interval of 600-700 msec. Tension increased the amplitude of TD's in Purkinje tissue and promoted the appearance of TD's in muscle. TD's in muscle occasionally reached threshold in the presence of tension. The results of this study suggest that stretch or increased resting tension may promote the types of cardiac arrhythmias that are causally related to digitalis-induced TD's. The results are compatible with the hypothesis that TD's are caused either by a transmembrane influx of calcium or by an internal release of calcium ions.
Effects of terbutaline and atenolol on large and small airways in asthmatic patients
Authors: JW Lammers, ME Muller, HT Folgering, CL van Herwaarden
Journal: European Respiratory Journal (1988)

In order to localize the main site of action of the beta 2-adrenoceptor selective agonist terbutaline and the beta 1-adrenoceptor selective antagonist atenolol in the airways of asthmatic patients, we compared the effects of these drugs on maximal expiratory flow-volume (MEFV) curves when breathing air and when breathing a helium-oxygen (HeO2) mixture. To investigate whether a shift in localization of the bronchodilator effect occurs when terbutaline is inhaled repeatedly, dose-response curves with terbutaline were performed for parameters derived from MEFV curves when breathing air and for density dependence of expiratory airflow. By measurement of MEFV curves when the patients were breathing air alone, it was not possible to determine whether there is a difference in the bronchoconstrictor effect of atenolol between large and small airways. Inhalation of terbutaline to a cumulative dose of 2.0 mg induced a stepwise improvement in expiratory airflow parameters for large and small airways function when breathing air. Doubling the dose of inhaled terbutaline to 4 mg did not result in any further improvement of lung function. Neither atenolol nor terbutaline induced significant mean changes in density dependence of expiratory airflow. This was partly due to large inter- and intra-individual variations of this parameter. Another possibility is that atenolol and terbutaline effect large and small airways function equally.
Aldosterone Activates NF-κB in the Collecting Duct
Authors: Vale[Combining Acute Accent]rie Leroy, Sophie De Seigneux, Victor Agassiz, Udo Hasler, Marie-Edith Rafestin-Oblin, Manlio Vinciguerra, Pierre-Yves Martin, Eric Fe[Combining Acute Accent]raille
Journal: Journal of the American Society of Nephrology (2008)

Besides its classical effects on salt homeostasis in renal epithelial cells, aldosterone promotes inflammation and fibrosis and modulates cell proliferation. The proinflammatory transcription factor NF-κB has been implicated in cell proliferation, apoptosis, and regulation of transepithelial sodium transport. The effect of aldosterone on the NF-κB pathway in principal cells of the cortical collecting duct, a major physiologic target of aldosterone, is unknown. Here, in both cultured cells and freshly isolated rat cortical collecting duct, aldosterone activated the canonical NF-κB signaling pathway, leading to increased expression of several NF-κB–targeted genes (IκBα, plasminogen activator inhibitor 1, monocyte chemoattractant protein 1, IL-1β, and IL-6). Small interfering RNA–mediated knockdown of the serum and glucocorticoid-inducible kinase SGK1, a gene induced early in the response to aldosterone, but not pharmacologic inhibition of extracellular signal–regulated kinase and p38 kinase, attenuated aldosterone-induced NF-κB activation. Pharmacologic antagonism or knockdown of the mineralocorticoid receptor prevented aldosterone-induced NF-κB activity. In addition, activation of the glucocorticoid receptor inhibited the transactivation of NF-κB by aldosterone. In agreement with these in vitro findings, spironolactone prevented NF-κB–induced transcriptional activation observed in cortical collecting ducts of salt-restricted rats. In summary, aldosterone activates the canonical NF-κB pathway in principal cells of the cortical collecting duct by activating the mineralocorticoid receptor and by inducing SGK1.
Disordered Eating Behavior in Individuals With Diabetes
Authors: Deborah L. Young-Hyman, Catherine L. Davis
Journal: Diabetes Care (2010)

This review was conducted to examine disordered eating behavior (DEB), including diagnosable eating disorders, in the context of diabetes. The use of criteria and assessment methods standardized on the healthy population is examined. Also considered is the need for modified assessment methods and classification of this behavior when evaluating patients with diabetes. Future directions for research are suggested.

Literature published from 1980 to present was examined using “eating disorders and diabetes” as search terms. Over 100 peer-reviewed articles were identified via PubMed, Cochrane Reviews, PsycInfo, etc. Bibliographies from articles were reviewed to ascertain additional publications. Cited articles include reviews and individual studies indicating experimental design (self as control, healthy control, or population estimate), assessment methods (self-report, questionnaires, and structured/clinical interviews), and use of standard diagnostic criteria. Not all relevant articles could be included. However, some older references (published before 2000) are included because they provide foundation literature from which our understanding of DEB in the population of patients with diabetes derives and/or are validation studies for measurement methods. Additional references pertinent to hypothesized mechanisms are cited.

Most studies, including those in a 2005 meta-analysis ( N = 8 case-controlled studies), tend to focus on young women with type 1 diabetes, usually between ages 15–35 years, when weight concerns, DEB, and eating disorders are at a high prevalence (1). Recent studies have included type 2 diabetic patients, minorities, and male patients (2–9). The diagnosis of diabetes has been associated with elevated rates of DEB and eating disorders, particularly when insulin omission is considered purging (1,8–11).

Diagnosed eating disorders and subclinical DEB have been associated with poorer health in individuals with type 1 diabetes. Early reports found prevalence rates of the co-occurrence of diabetes and DEB to be low and accompanied by psychiatric comorbidity and weight …