tbuckley/cabot-search huggingface dataset:
Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture.
Authors: M Ishibashi, T Yamaji
Journal: Journal of Clinical Investigation (1984)

To determine the mechanism and the site of action of catecholamines as well as hormones including thyrotropin-releasing hormone (TRH)1 and somatostatin on pituitary hormone release in patients with acromegaly and in normal subjects, the effects of these substances on growth hormone (GH) and prolactin (PRL) secretion from adenomatous and nonadenomatous human pituitary cells in culture were examined. When dopamine (0.01-0.1 microM) or bromocriptine (0.01-0.1 microM) was added to the culture media, a significant inhibition of GH and PRL secretion from adenoma cells from acromegalic patients was observed. This inhibition was blocked by D2 receptor blockade with metoclopramide or sulpiride, but not by D1 receptor blockade. Similarly, dopamine suppressed GH and PRL release by nonadenomatous pituitary cells in a dose-dependent manner, which was again blocked by D2 receptor blockade. The minimum effective concentration of dopamine required for a significant inhibition of PRL secretion (0.01 microM) was lower than that for GH release (0.1 microM). Norepinephrine, likewise, caused a suppression of PRL secretion from adenomatous and nonadenomatous pituitary cells. This effect was blocked by sulpiride, phentolamine, however, was ineffective. When TRH was added to the media, both GH and PRL secretion were enhanced in adenoma cells, while only the stimulation of PRL release was observed in nonadenomatous pituitary cells. Coincubation of TRH and dopamine resulted in variable effects on GH and PRL secretion. Somatostatin consistently lowered GH and PRL secretion in both adenomatous and nonadenomatous pituitary cells and completely blocked the TRH-induced stimulation of GH and PRL secretion from adenoma cells. Opioid peptides (1 microM) failed to affect hormone release. These results suggest that no qualitative difference in GH and PRL responses to dopaminergic agonists or to somatostatin exists between adenoma cells of acromegalic patients and normal pituitary cells, and that the direct effect of catecholamines on GH and PRL secretion from human pituitary cells is mediated mainly through dopamine receptor activation.
Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis
Authors: M Ruhwald, T Bodmer, C Maier, M Jepsen, M B Haaland, J Eugen-Olsen, P Ravn
Journal: European Respiratory Journal (2008)

The aim of the present study was to evaluate the potential of diagnostic tests based on interferon-γ inducible protein (IP)-10 and monocyte chemotactic protein (MCP)-2, and compare the performance with the QuantiFERON TB® Gold In-Tube (QFT-IT; Cellestis, Carnagie, Australia) test. IP-10 and MCP-2 were determined in supernatants from whole blood stimulated with <i>Mycobacterium tuberculosis</i>-specific antigens. Samples were obtained from 80 patients with culture- and/or PCR-proven tuberculosis (TB), and 124 unexposed healthy controls: 86 high school students and 38 high school staff. IP-10 and MCP-2 test cut-offs were established based on receiver operating characteristic curve analysis. TB patients produced significantly higher levels (median) of IP-10 (2158 pg·mL<sup>−1</sup>) and MCP-2 (379 pg·mL<sup>−1</sup>) compared with interferon (IFN)-γ (215 pg·mL<sup>−1</sup>). The QFT-IT, IP-10 and MCP-2 tests detected 81, 83 and 71% of the TB patients; 0, 3 and 0% of the high school students and 0, 16 and 3% of the staff, respectively. Agreement between tests was high (&gt;89%). By combining IP-10 and IFN-γ tests, the detection rate increased among TB patients to 90% without a significant increase in positive responders among the students. In conclusion, interferon-γ inducible protein-10 and monocyte chemotactic protein-2 responses to<i> Mycobacterium tuberculosis</i>-specific antigens could be used to diagnose infection. Combining interferon-γ inducible protein-10 and interferon-γ may be a simple approach to increase the detection rate of the <i>Mycobacterium tuberculosis</i>-specific <i>in vitro</i> tests.
Designing and implementing a COPD discharge care bundle
Authors: Nicholas S Hopkinson, Catherine Englebretsen, Nicholas Cooley, Kevin Kennie, Mun Lim, Thomas Woodcock, Anthony A Laverty, Sandra Wilson, Sarah L Elkin, Cielito Caneja, Christine Falzon, Helen Burgess, Derek Bell, Dilys Lai
Journal: Thorax (2011)

National surveys have revealed significant differences in patient outcomes following admission to hospital with acute exacerbation of COPD which are likely to be due to variations in care. We developed a care bundle, comprising a short list of evidence-based practices to be implemented prior to discharge for all patients admitted with this condition, based on a review of national guidelines and other relevant literature, expert opinion and patient consultation. Implementation was then piloted using action research methodologies with patient input. Actively involving staff was vital to ensure that the changes introduced were understood and the process followed. Implementation of a care bundle has the potential to produce a dramatic improvement in compliance with optimum health care practice.
<i>mda</i>-9/Syntenin: More than Just a Simple Adapter Protein When It Comes to Cancer Metastasis
Authors: Devanand Sarkar, Habib Boukerche, Zao-zhong Su, Paul B. Fisher
Journal: Cancer Research (2008)

Abstract Cancer is a progressive disease that, in many instances, if untreated, can culminate in metastatic spread of primary tumor cells to distant sites in the body. Metastasis frequently confers virulence and therapy resistance to cancer cells, and defining the molecular events that control metastasis will be mandatory to develop rational, targeted therapies for effective intervention, prevention of recurrence, and the “holy grail” of engendering a cure. Adapter proteins are physiologically pertinent molecules that, through interactions with key regulatory proteins via specific conserved domains, control important cellular events. Melanoma differentiation associated gene-9 (mda-9), also known as syntenin, is a PDZ domain–containing adapter protein that is involved in organization of protein complexes in the plasma membranes, regulation of B-cell development, intracellular trafficking and cell-surface targeting, synaptic transmission, and axonal outgrowth. Recent studies now define a seminal role for mda-9/sytenin in cancer metastasis. The present review provides a current perspective of our understanding of this important aspect of mda-9/sytenin, suggesting that this gene and its encoded protein and interacting protein partners may provide viable targets for intervening in the final and invariably the most lethal stage of cancer progression, namely, cancer metastasis. [Cancer Res 2008;68(9):3087–93]
Reply to N.-K.V. Cheung et al
Authors: Katherine K. Matthay, Wendy B. London, John Maris, Peter C. Adamson, Julie R. Park
Journal: Journal of Clinical Oncology (2014)

The randomized trial reported by Matthay et al1 used event-free survival (EFS) as the primary end point, which has been sustained as significant even in an unplanned later long-term follow-up: 5-year EFS for autologous bone marrow transplant (ABMT), 30%; chemotherapy consolidation, 19% (P = .04).1,2 Although overall survival (OS) was not statistically significant, in the analysis of all four randomized arms, 5-year OS for ABMT with isotretinoin was higher than both non-ABMT arms (P = .054; Fig 4B1), even though this was an unplanned analysis for these subgroups.1 As noted by Cheung et al,3 the only two additional randomized trials showed a significant advantage for ABMT over conventional chemotherapy.4,5 It is noteworthy that the Children’s Cancer Group trial used an intensive chemotherapy comparison arm to ABMT with similar hospitalization days, death related to toxicity rate, and second malignancy, and still showed a significant advantage in EFS for the ABMT arm.2
DNA Methylation in Anal Intraepithelial Lesions and Anal Squamous Cell Carcinoma
Authors: Jun Zhang, Ciro R. Martins, Zoya B. Fansler, Kristina L. Roemer, Erik A. Kincaid, Karen S. Gustafson, Daniel F. Heitjan, Douglas P. Clark
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Anal intraepithelial neoplasia is associated with human papillomavirus infection and may progress to invasive squamous cell carcinoma (SCC), which is increasing in immunocompromised patients. We hypothesize that anal intraepithelial neoplasia is associated with abnormal DNA methylation and that detection of these events may be used to improve screening programs. Experimental Design: Seventy-six patients were identified who underwent anal cytology screening and subsequent biopsy at our institution between 1999 and 2004. The specimens from these patients included 184 anal biopsies [normal, n = 57; low-grade squamous intraepithelial lesion (LSIL), n = 74; high-grade squamous intraepithelial lesion (HSIL), n = 41; and invasive SCC, n = 12] and 37 residual liquid-based anal cytology specimens (normal, n = 11; LSIL, n = 12; HSIL, n = 14). The methylation status of the following genes was determined for each biopsy and cytology sample using real-time methylation-specific PCR: HIC1, RASSF1, RARB, CDKN2A, p14, TP73, APC, MLH1, MGMT, DAPK1, and IGSF4. Results: Methylation-specific PCR analysis of biopsy samples revealed that DNA methylation was more common in SCC and HSIL than LSIL and normal mucosa. Specifically, methylation of IGSF4 and DAPK1 was prevalent in SCC (75% and 75% of cases, respectively) and HSIL (59% and 71%, respectively) but was absent in LSIL and normal biopsy samples. Methylation profiles of cytologic samples were similar to those found in the biopsy samples. Conclusions: Aberrant DNA methylation is a frequent event in anal HSIL and SCC. Methylation of IGSF4 and DAPK1 is specific for HSIL and SCC, and may serve as a useful molecular biomarker.
Contribution of ABL Kinase Domain Mutations to Imatinib Resistance in Different Subsets of Philadelphia-Positive Patients: By the GIMEMA Working Party on Chronic Myeloid Leukemia
Authors: Simona Soverini, Sabrina Colarossi, Alessandra Gnani, Gianantonio Rosti, Fausto Castagnetti, Angela Poerio, Ilaria Iacobucci, Marilina Amabile, Elisabetta Abruzzese, Ester Orlandi, Franca Radaelli, Fabrizio Ciccone, Mario Tiribelli, Roberto di Lorenzo, Clementina Caracciolo, Barbara Izzo, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Giovanni Martinelli
Journal: Clinical Cancer Research (2006)

Abstract Purpose: ABL kinase domain mutations have been implicated in the resistance to the BCR-ABL inhibitor imatinib mesylate of Philadelphia-positive (Ph+) leukemia patients. Experimental Design: Using denaturing high-performance liquid chromatography and sequencing, we screened for ABL kinase domain mutations in 370 Ph+ patients with evidence of hematologic or cytogenetic resistance to imatinib. Results: Mutations were found in 127 of 297 (43%) evaluable patients. Mutations were found in 27% of chronic-phase patients (14% treated with imatinib frontline; 31% treated with imatinib post-IFN failure), 52% of accelerated-phase patients, 75% of myeloid blast crisis patients, and 83% of lymphoid blast crisis/Ph+ acute lymphoblastic leukemia (ALL) patients. Mutations were associated in 30% of patients with primary resistance (44% hematologic and 28% cytogenetic) and in 57% of patients with acquired resistance (23% patients who lost cytogenetic response; 55% patients who lost hematologic response; and 87% patients who progressed to accelerated phase/blast crisis). P-loop and T315I mutations were particularly frequent in advanced-phase chronic myeloid leukemia and Ph+ ALL patients, and often accompanied progression from chronic phase to accelerated phase/blast crisis. Conclusions: We conclude that (a) amino acid substitutions at seven residues (M244V, G250E, Y253F/H, E255K/V, T315I, M351T, and F359V) account for 85% of all resistance-associated mutations; (b) the search for mutations is important both in case of imatinib failure and in case of loss of response at the hematologic or cytogenetic level; (c) advanced-phase chronic myeloid leukemia and Ph+ ALL patients have a higher likelihood of developing imatinib-resistant mutations; and (d) the presence of either P-loop or T315I mutations in imatinib-treated patients should warn the clinician to reconsider the therapeutic strategy.
Artemin causes hypersensitivity to warm sensation, mimicking warmth-provoked pruritus in atopic dermatitis
Authors: Hiroyuki Murota, Mayuko Izumi, Mostafa I.A. Abd El-Latif, Megumi Nishioka, Mika Terao, Mamori Tani, Saki Matsui, Shigetoshi Sano, Ichiro Katayama
Journal: Journal of Allergy and Clinical Immunology (2012)
Stretch-induced alternative splicing of serum response factor promotes bronchial myogenesis and is defective in lung hypoplasia
Authors: Yan Yang, Safedin Beqaj, Paul Kemp, Ilana Ariel, Lucia Schuger
Journal: Journal of Clinical Investigation (2000)

Smooth muscle (SM) develops only in organs and sites that sustain mechanical tensions. Therefore, we determined the role of stretch in mouse and human bronchial myogenesis. Sustained stretch induced expression of SM proteins in undifferentiated mesenchymal cells and accelerated the differentiation of cells undergoing myogenesis. Moreover, bronchial myogenesis was entirely controlled in lung organ cultures by the airway intraluminal pressure. Serum response factor (SRF) is a transcription factor critical for the induction of muscle-specific gene expression. Recently, a SRF-truncated isoform produced by alternative splicing of exon 5 has been identified (SRFΔ5). Here we show that undifferentiated mesenchymal cells synthesize both SRF and SRFΔ5 but that SRFΔ5 synthesis is suppressed during bronchial myogenesis in favor of increased SRF production. Stretch induces the same change in SRF alternative splicing, and its myogenic effect is abrogated by overexpressing SRFΔ5. Furthermore, human hypoplastic lungs related to conditions that hinder cell stretching continue to synthesize SRFΔ5 and show a marked decrease in bronchial and interstitial SM cells and their ECM product, tropoelastin. Taken together, our findings indicate that stretch plays a critical role in SM myogenesis and suggest that its decrease precludes normal bronchial muscle development.
Vaccination by Genetically Modified Dendritic Cells Expressing a Truncated<b><i>neu</i></b>Oncogene Prevents Development of Breast Cancer in Transgenic Mice
Authors: Yoshio Sakai, Brian J. Morrison, J. Douglas Burke, Jong-Myun Park, Masaki Terabe, John E. Janik, Guido Forni, Jay A. Berzofsky, John C. Morris
Journal: Cancer Research (2004)

Abstract Dendritic cells (DCs) are powerful antigen-presenting cells that process antigens and present peptide epitopes in the context of the major histocompatibility complex molecules to generate immune responses. DCs are being studied as potential anticancer vaccines because of their ability to present antigens to naïve T cells and to stimulate the expansion of antigen-specific T-cell populations. We investigated an antitumor vaccination using DCs modified by transfer of a nonsignaling neu oncogene, a homologue of human HER-2/neu, in a transgenic model of breast cancer. BALB-neuT mice develop breast cancers as a consequence of mammary gland-specific expression of an activated neu oncogene. We vaccinated BALB-neuT mice with bone marrow-derived DCs transduced with Ad.Neu, a recombinant adenovirus expressing a truncated neu oncoprotein. The vaccine stimulated the production of specific anti-neu antibodies, enhanced interferon-γ expression by T cells, and prevented or delayed the onset of mammary carcinomas in the mice. Over 65% of vaccinated mice remained tumor free at 28 weeks of age, whereas all of the mice in the control groups developed tumors. When challenged with a neu-expressing breast cancer cell line, vaccinated tumor-free animals had delayed tumor growth compared with controls. The antitumor effect of the vaccine was specific for expression of neu. Studies showed that CD4+ T cells were required in order to generate antitumor immunity. Importantly, the effectiveness of the vaccine was not diminished by preexisting immunity to adenovirus, whereas the protection afforded by vaccination that used direct injection of Ad.Neu was markedly reduced in mice with anti-adenovirus antibody titers. DCs modified by recombinant adenoviruses expressing tumor-associated antigens may provide an effective antitumor vaccination strategy.
Redox regulation of cardiac calcium channels and transporters
Authors: A ZIMA, L BLATTER
Journal: Cardiovascular Research (2006)

Intracellular concentrations of redox-active molecules can significantly increase in the heart as a result of activation of specific signal transduction pathways or the development of certain pathophysiological conditions. Changes in the intracellular redox environment can affect many cellular processes, including the gating properties of ion channels and the activity of ion transporters. Because cardiac contraction is highly dependent on intracellular Ca(2+) levels ([Ca(2+)](i)) and [Ca(2+)](i) regulation, redox modification of Ca(2+) channels and transporters has a profound effect on cardiac function. The sarcoplasmic reticulum (SR) Ca(2+) release channel, or ryanodine receptor (RyR), is one of the well-characterized redox-sensitive ion channels in the heart. The redox modulation of RyR activity is mediated by the redox modification of sulfhydryl groups of cysteine residues. Other key components of cardiac excitation-contraction (e-c) coupling such as the SR Ca(2+) ATPase and L-type Ca(2+) channel are subject to redox modulation. Redox-mediated alteration of the activity of ion channels and pumps is directly involved in cardiac pathologies such as ischemia-reperfusion injury. Significant bursts of reactive oxygen species (ROS) generation occur during reperfusion of the ischemic heart, and changes in the activity of the major components of [Ca(2+)](i) regulation, such as RyR, Na(+)-Ca(2+) exchange and Ca(2+) ATPases, are likely to play an important role in ischemia-related Ca(2+) overload. This article summarizes recent findings on redox regulation of cardiac Ca(2+) transport systems and discusses contributions of this redox regulation to normal and pathological cardiac function.
Monitoring CD4 counts in HIV infection
Authors: V. Harindra, R. Basu Roy, AndrewM. Hili, Theresa Ekong, Colin Clark, Mark Gompels, AnthonyJ. Pinching, Andrew Phillips, ChristineA. Lee, Jonathan Elford, George Janossy, PeterB.A. Kernoff
Journal: The Lancet (1991)
High-dose paclitaxel plus G-CSF for malignant mesothelioma: CALGB phase II study 9234
Authors: N J Vogelzang, J E Herndon, A Miller, G Strauss, G Clamon, F M Stewart, J Aisner, A Lyss, M R Cooper, Y Suzuki, M R Green
Journal: Annals of Oncology (1999)
Leptin Promotes Fibroproliferative Acute Respiratory Distress Syndrome by Inhibiting Peroxisome Proliferator–activated Receptor-γ
Authors: Manu Jain, G. R. Scott Budinger, Amy Lo, Daniela Urich, Stephanie E. Rivera, Asish K. Ghosh, Angel Gonzalez, Sergio E. Chiarella, Katie Marks, Helen K. Donnelly, Saul Soberanes, John Varga, Kathryn A. Radigan, Navdeep S. Chandel, Gökhan M. Mutlu
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Diabetic patients have a lower incidence of acute respiratory distress syndrome (ARDS), and those who develop ARDS are less likely to die. The mechanisms that underlie this protection are unknown.Objectives: To determine whether leptin resistance, a feature of diabetes, prevents fibroproliferation after lung injury.Methods: We examined lung injury and fibroproliferation after the intratracheal instillation of bleomycin in wild-type and leptin-resistant (db/db) diabetic mice. We examined the effect of leptin on transforming growth factor (TGF)-β1–mediated transcription in primary normal human lung fibroblasts. Bronchoalveolar lavage fluid (BAL) samples from patients with ARDS and ventilated control subjects were obtained for measurement of leptin and active TGF-β1 levels.Measurements and Main Results: Diabetic mice (db/db) were resistant to lung fibrosis. The db/db mice had higher levels of peroxisome proliferator–activated receptor-γ (PPARγ), an inhibitor of the transcriptional response to TGF-β1, a cytokine critical in the pathogenesis of fibroproliferative ARDS. In normal human lung fibroblasts, leptin augmented the transcription of profibrotic genes in response to TGF-β1 through a mechanism that required PPARγ. In patients with ARDS, BAL leptin levels were elevated and correlated with TGF-β1 levels. Overall, there was no significant relationship between BAL leptin levels and clinical outcomes; however, in nonobese patients, higher BAL leptin levels were associated with fewer intensive care unit– and ventilator-free days and higher mortality.Conclusions: Leptin signaling is required for bleomycin-induced lung fibrosis. Leptin augments TGF-β1 signaling in lung fibroblasts by inhibiting PPARγ. These findings provide a mechanism for the observed protection against ARDS observed in diabetic patients.
LOCALIZATION OF ADRENOCORTICOTROPIC HORMONE BY HISTOCHEMICAL AND IMMUNOCHEMICAL METHODS
Authors: John M. Marshall
Journal: The Journal of Experimental Medicine (1951)

The fluorescent antibody technique was adapted to the localization of native protein antigens in cells and tissues. This method was applied specifically to the localization of adrenocorticotropic hormone in the pituitary gland. An antiserum to hog ACTH was produced in an adrenalectomized rabbit. The gamma(2)-globulin fraction of the serum was conjugated with fluorescein. After purification, the fluorescent antibody solution stained selectively the cytoplasm of basophil cells of the hog pituitary. No cells of sheep or beef pituitary or of hog kidney were stained. A fluorescent globulin solution prepared from normal rabbit serum gave no selective staining in any of these tissues. Immunochemical tests showed that the fluorescent antibody gave a precipitin reaction with a highly active ACTH preparation of low molecular weight. The supernatant solution from this reaction showed a loss of hormone activity.
Brief Communication: High Incidence of Venous Thrombotic Events among Patients with Wegener Granulomatosis: The Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study
Authors: Peter A. Merkel, Grace H. Lo, Janet T. Holbrook, Andrea K. Tibbs, Nancy B. Allen, John C. Davis, Gary S. Hoffman, W. Joseph McCune, E. William St. Clair, Ulrich Specks, Robert Spiera, Michelle Petri, John H. Stone
Journal: Annals of Internal Medicine (2005)

Venous thrombotic events (VTEs) have been observed in Wegener granulomatosis, but the incidence rate is not known.To measure the incidence of VTEs in patients with Wegener granulomatosis.Prospective, observational cohort study.A multicenter, randomized, double-blind, placebo-controlled treatment trial for Wegener granulomatosis.180 patients with Wegener granulomatosis enrolled during periods of active disease.Venous thrombotic events (deep venous thromboses or pulmonary emboli) were documented and confirmed prospectively. Incidence rates were calculated on the basis of time to first VTE.Thirteen patients had VTEs before enrollment. During 228 person-years of prospective follow-up, 16 VTEs occurred in 167 patients with no history of VTE. Median time from enrollment to VTE for patients with an event was 2.1 months. The incidence of VTE among patients with Wegener granulomatosis was 7.0 per 100 person-years (95% CI, 4.0 to 11.4).Although prospectively recorded, screening for VTEs did not occur.The incidence rate of VTEs in Wegener granulomatosis is high when compared with available rates in the general population, patients with lupus, and patients with rheumatoid arthritis. These results have important implications for clinical care of patients with Wegener granulomatosis.