tbuckley/cabot-search huggingface dataset:
Randomized Phase II Trial of Docetaxel Plus Thalidomide in Androgen-Independent Prostate Cancer
Authors: William L. Dahut, James L. Gulley, Philip M. Arlen, Yinong Liu, Katherine M. Fedenko, Seth M. Steinberg, John J. Wright, Howard Parnes, Clara C. Chen, Elizabeth Jones, Catherine E. Parker, W. Marston Linehan, William D. Figg
Journal: Journal of Clinical Oncology (2004)

Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC.Seventy-five patients with chemotherapy-naïve metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m(2) intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression.After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P =.32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group.In this randomized phase II trial, the addition of thalidomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination.
CD36-mediated cholesterol efflux is associated with PPARγ activation via a MAPK-dependent COX-2 pathway in macrophages
Authors: Kim Bujold, David Rhainds, Christian Jossart, Maria Febbraio, Sylvie Marleau, Huy Ong
Journal: Cardiovascular Research (2009)

Growth hormone-releasing peptides (GHRPs) as CD36 selective ligands feature potent anti-atherosclerotic activity that is associated with an upregulation of the peroxisome proliferator-activated receptor gamma (PPARgamma)-liver X receptor alpha (LXRalpha)-ATP-binding cassette (ABC) transporter pathway. However, the mechanism involved in PPARgamma activation in response to CD36 signalling has yet to be determined. Therefore, the present study aims to elucidate the upstream molecular mechanisms through which EP 80317, a selective CD36 ligand, promotes lipid efflux from macrophages through PPARgamma activation.[3H]-Cholesterol- and [3H]-methylcholine chloride-labelled murine macrophages treated with EP 80317 showed a significant increase in cholesterol and phospholipid efflux to both apolipoprotein A-I and high-density lipoprotein in a CD36-dependent manner. Lipid efflux was associated with enhanced activation of PPARgamma. The signalling pathway by which this CD36 ligand promoted lipid efflux involved an increase in intracellular 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) levels induced by extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent cyclooxygenase-2 (COX-2) expression, leading to PPARgamma activation. In agreement, EP 80317-mediated cholesterol efflux was abrogated by inhibitors of PPARgamma, ERK1/2, and COX-2 as well as ABC transporter inhibitors, whereas a p38 mitogen-activated protein kinase inhibitor had no effect.These findings suggest a central role for the prostanoid 15d-PGJ2 in PPARgamma activation and the upregulation of the ABC transporter pathway in response to CD36 activation by synthetic GHRPs analogues. The resulting enhanced cholesterol efflux might explain, at least in part, the atheroprotective effect of selective CD36 ligands.
Classical protein kinase C and its hypoxic stimulus-induced translocation in the cat and rat carotid body
Authors: M. Pokorski, H. Sakagami, H. Kondo
Journal: European Respiratory Journal (2000)

The presence, subcellular distribution, species specificity and possible hypoxic stimulus-induced translocation of classical protein kinase C (cPKC) isozymes were examined in the carotid body. Carotid bodies were dissected from cats exposed in vivo to normoxic or acute hypoxic conditions and from normoxic rats. For immunohistochemistry isoform-specific monoclonal antisera to PKCalpha, PKCbetaI, PKCbetaII and PKCgamma were used. The immunoreactivity was visualized by fluorescein isothiocyanate (FITC) labelling. FITC/Texas red double-labelled specimens for the cPKC isozymes/tyrosine hydroxylase were used to demonstrate the chemoreceptor cell localization of cPKC isozymes. The immunofluorescence was detected using laser scanning confocal image technology. The results showed expression of the PKCalpha and PKCgamma but not PKCbeta isoforms in the cytoplasm of carotid body chemoreceptor cells. The double labelling provided evidence for the chemoreceptor cell localization of the cPKC isoforms detected. The immunostaining was most intense in the periphery of the perikarya, the nuclear envelope and, occasionally, the nucleoplasm. No major differences were found in the immunolocalization of PKCalpha and PKCgamma under normoxic and hypoxic conditions or between species. However, the immunoreactivity tended to accumulate more in the peripheral cytoplasm and away from the nucleus in the hypoxic chemoreceptor cell. This study demonstrates the presence of classical protein kinase C enzymes in chemoreceptor cells. The intensity of the immunoreactivity may suggest a role for the classical protein kinase C signalling pathway in shaping the hypoxic response at the carotid body. However, this study failed to provide firm evidence of this.
Mixed-Lineage Kinases: A Target for the Prevention of Neurodegeneration
Authors: Leo H. Wang, Cagri G. Besirli, Eugene M. Johnson
Journal: The Annual Review of Pharmacology and Toxicology (2004)

The activation of the c-Jun N-terminal kinase (JNK) pathway is critical for naturally occurring neuronal cell death during development and may be important for the pathological neuronal cell death of neurodegenerative diseases. The small molecule inhibitor of the mixed-lineage kinase (MLK) family of kinases, CEP-1347, inhibits the activation of the JNK pathway and, consequently, the cell death in many cell culture and animal models of neuronal death. CEP-1347 has the ability not only to inhibit cell death but also to maintain the trophic status of neurons in culture. The possible importance of the JNK pathway in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases provides a rationale for the use of CEP-1347 for the treatment of these diseases. CEP-1347 has the potential of not only retarding disease progression but also reversing the severity of symptoms by improving the function of surviving neurons.
The Biology of Interleukin-2
Authors: Thomas R. Malek
Journal: Annual Review of Immunology (2007)

Much data support an essential role for interleukin (IL)-2 in immune tolerance. This idea is much different from the early paradigm in which IL-2 is central for protective immune responses. This change in thinking occurred when a T regulatory cell defect was shown to be responsible for the lethal autoimmunity associated with IL-2/IL-2R deficiency. This realization allowed investigators to explore immune responses in IL-2-nonresponsive mice rendered autoimmune-free. Such studies established that IL-2 sometimes contributes to optimal primary immune responses, but it is not mandatory. Emerging findings, however, suggest an essential role for IL-2 in immune memory. Here, the current understanding of the dual role of IL-2 in maintaining tolerance and contributing to immunity in vivo is reviewed with some emphasis on T regulatory cell production and homeostasis. Also discussed are implications of this new appreciation concerning the immunobiology of IL-2 with respect to targeting IL-2 or its receptor in immunotherapy.
FDA-PPTA Workshop
Authors: Lester M. Crawford, Jr
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
D2 Dopamine Receptor Gene Is Associated but Not Linked With Alcoholism
Authors: C. Robert Cloninger
Journal: JAMA (1991)

There has been intense interest in replicating the 1990 report in<i>JAMA</i>that the minor allele of<i>DRD2</i>(the D<sub>2</sub>dopamine receptor gene on human chromosome 11 at q22-q23) may increase susceptibility to severe alcoholism in some cases. In May 1990 Blum et al<sup>1</sup>reported that 24 (69%) of 35 alcoholics carried the Al allele of<i>DRD2</i>compared with only seven (20%) of 35 nonalcoholics. Their analysis was based on brain tissue of deceased subjects, and the alcoholics were described as having experienced repeated treatment failures in their alcoholism rehabilitation, with their deaths attributable primarily to the chronic damaging effects of alcohol. It was surprising that a single gene could be so strongly associated with a common disorder that is known to be developmentally complex and genetically heterogeneous.<sup>2</sup>Accordingly, there was caution and skepticism about the report because of its small sample size and the surprising strength
Reply: The Alveolar Macrophage and Acute Respiratory Distress Syndrome: A Silent Actor?
Authors: Laura C. Barr, Mairi Brittan, Andrew Conway Morris, Daniel F. McAuley, Chiara McCormack, Alison M. Fletcher, Hamish Richardson, Martin Connell, Dilip Patel, William A. H. Wallace, Adriano G. Rossi, Donald J. Davidson, Lynn Manson, Marc Turner, Nikhil Hirani, Timothy S. Walsh, Niall H. Anderson, Kevin Dhaliwal, A. John Simpson
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Human IgM Monoclonal Antibody 16.88: Pharmacokinetics and Immunogenicity in Colorectal Cancer Patients
Authors: H. J. Haisma, H. M. Pinedo, M. A. P. Kessel, M. van Muijen, E. Boven, J. C. Roos, M. A. B. D. Plaizier, H. J. M. Martens, R. Dejager
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Human IgM Monoclonal Antibody 16.88: Pharmacokinetics and Immunogenicity in Colorectal Cancer Patients Get access Hidde J. Haisma, Hidde J. Haisma * 1Department of Oncology, Free University HospitalAmsterdam, The Netherlands * Hidde J. Haisma, Ph.D., Free University Hospital P.O.Box 7057, 1007 MB Amsterdam, The Netherlands. Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert M. Pinedo, Herbert M. Pinedo 1Department of Oncology, Free University HospitalAmsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Mieke A. P. Kessel, Mieke A. P. Kessel 1Department of Oncology, Free University HospitalAmsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Monique van Muijen, Monique van Muijen 1Department of Oncology, Free University HospitalAmsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Epie Boven, Epie Boven 1Department of Oncology, Free University HospitalAmsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Jan C. Roos, Jan C. Roos Department of Nuclear Medicine, Free University HospitalAmsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Marian A. B. D. Plaizier, Marian A. B. D. Plaizier Department of Nuclear Medicine, Free University HospitalAmsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Harrie J. M. Martens, Harrie J. M. Martens Department of Pharmacy, Free University Hospital AmsterdamAmsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Dejager Robert Dejager Biotechnlogy Research InstituteRockville, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 24, 18 December 1991, Pages 1813–1819, https://doi.org/10.1093/jnci/83.24.1813 Published: 18 December 1991 Article history Received: 22 April 1991 Revision received: 30 August 1991 Accepted: 27 September 1991 Published: 18 December 1991
Human T <sub>H</sub> 9 Cells Are Skin-Tropic and Have Autocrine and Paracrine Proinflammatory Capacity
Authors: Christoph Schlapbach, Ahmed Gehad, Chao Yang, Rei Watanabe, Emmanuella Guenova, Jessica E. Teague, Laura Campbell, Nikhil Yawalkar, Thomas S. Kupper, Rachael A. Clark
Journal: Science Translational Medicine (2014)

T helper type 9 (TH9) cells can mediate tumor immunity and participate in autoimmune and allergic inflammation in mice, but little is known about the TH9 cells that develop in vivo in humans. We isolated T cells from human blood and tissues and found that most memory TH9 cells were skin-tropic or skin-resident. Human TH9 cells coexpressed tumor necrosis factor-α and granzyme B and lacked coproduction of TH1/TH2/TH17 cytokines, and many were specific for Candida albicans. Interleukin-9 (IL-9) production was transient and preceded the up-regulation of other inflammatory cytokines. Blocking studies demonstrated that IL-9 was required for maximal production of interferon-γ, IL-9, IL-13, and IL-17 by skin-tropic T cells. IL-9-producing T cells were increased in the skin lesions of psoriasis, suggesting that these cells may contribute to human inflammatory skin disease. Our results indicate that human TH9 cells are a discrete T cell subset, many are tropic for the skin, and although they may function normally to protect against extracellular pathogens, aberrant activation of these cells may contribute to inflammatory diseases of the skin.
Regulation of Iron Metabolism by Hepcidin
Authors: Elizabeta Nemeth, Tomas Ganz
Journal: Annual Review of Nutrition (2006)

▪ Abstract Hepcidin, a peptide hormone made in the liver, is the principal regulator of systemic iron homeostasis. Hepcidin controls plasma iron concentration and tissue distribution of iron by inhibiting intestinal iron absorption, iron recycling by macrophages, and iron mobilization from hepatic stores. Hepcidin acts by inhibiting cellular iron efflux through binding to and inducing the degradation of ferroportin, the sole known cellular iron exporter. Synthesis of hepcidin is homeostatically increased by iron loading and decreased by anemia and hypoxia. Hepcidin is also elevated during infections and inflammation, causing a decrease in serum iron levels and contributing to the development of anemia of inflammation, probably as a host defense mechanism to limit the availability of iron to invading microorganisms. At the opposite side of the spectrum, hepcidin deficiency appears to be the ultimate cause of most forms of hemochromatosis, either due to mutations in the hepcidin gene itself or due to mutations in the regulators of hepcidin synthesis. The emergence of hepcidin as the pathogenic factor in most systemic iron disorders should provide important opportunities for improving their diagnosis and treatment.
Beryllium: A Modern Industrial Hazard
Authors: Kathleen Kreiss, Gregory A. Day, Christine R. Schuler
Journal: Annual Review of Public Health (2006)

Beryllium exposure can cause a granulomatous lung disease in workers who develop a lymphocyte-mediated sensitization to the metal. Workers in diverse industries are at risk because beryllium's properties are critical to nuclear, aerospace, telecommunications, electronic, metal alloy, biomedical, and semiconductor industries. The occupational air concentration standard's failure to protect beryllium workers is driving many scientific and occupational health advances. These developments include study of bioavailability of different physicochemical forms of beryllium, medical surveillance to show effectiveness of skin protection in preventing sensitization in high-risk processes, gene-environment interaction, transgenic mice for use in experimental research, and risk-based management of industrial exposures in the absence of effective exposure-response information. Beryllium sensitization and disease prevention are paradigms for much broader public health action in both occupational and general population settings.
826-4 B-type natriuretic peptide levels on admission predict short-term mortality and angiographic success of procedure in patients with acute ST elevation myocardial infarction treated with primary angioplasty
Authors: Marcin Grabowski, Krzysztof J Filipiak, Grzegorz Karpinski, Adam Rdzanek, Arkadiusz Pietrasik, Zenon Huczek, Grzegorz Horszczaruk, Janusz Kochman, Grzegorz Opolski
Journal: Journal of the American College of Cardiology (2004)
Frequency Function of Transit Times through Dog Pulmonary Circulation
Authors: ATTILIO MASERI, PAOLO CALDINI, SOLBERT PERMUTT, KENNETH L. ZIERLER
Journal: Circulation Research (1970)

The frequency function of transit times through the pulmonary vascular system in dogs was obtained by deconvolution of a pair of simultaneous tracer dilution curves. One tracer dilution curve represented transit times from pulmonary artery to aorta; the other represented transit times from left atrium to aorta. Theory of and requirements for deconvolution are presented. Two preparations were used: closed chest with recirculation, open chest with only myocardial recirculation. The frequency function of pulmonary vascular transit times was skewed markedly to the right. At constant cardiac output and left atrial pressure it was unaffected by change in heart rate or by respiratory movements. Frequency functions of transit time obtained by deconvolution of observed tracer concentration curves, including recirculation, were compared with those obtained by monoexponential extrapolation of the same tracer concentration curves to "eliminate" recirculation. If recirculation seemed to appear before the observed concentration curve (aortic sampling following pulmonary arterial injection) fell to 20% of peak, monoexponential extrapolation led to a 10% overestimate of mean transit time and to greater errors in estimate of higher moments. If recirculation did not seem to occur until the concentration fell to 10% or less of peak, there was no difference between the frequency functions of transit times calculated by the two methods. Increased coefficients of variance and skewness were associated with large mean transit times produced by hypovolemia and reduced cardiac output secondary to withdrawal of blood.
B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma
Authors: Robert O. Carpenter, Moses O. Evbuomwan, Stefania Pittaluga, Jeremy J. Rose, Mark Raffeld, Shicheng Yang, Ronald E. Gress, Frances T. Hakim, James N. Kochenderfer
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Multiple myeloma is a usually incurable malignancy of plasma cells. New therapies are urgently needed for multiple myeloma. Adoptive transfer of chimeric antigen receptor (CAR)–expressing T cells is a promising new therapy for hematologic malignancies, but an ideal target antigen for CAR-expressing T-cell therapies for multiple myeloma has not been identified. B-cell maturation antigen (BCMA) is a protein that has been reported to be selectively expressed by B-lineage cells including multiple myeloma cells. Our goal was to determine if BCMA is a suitable target for CAR-expressing T cells. Experimental Design: We conducted an assessment of BCMA expression in normal human tissues and multiple myeloma cells by flow cytometry, quantitative PCR, and immunohistochemistry. We designed and tested novel anti-BCMA CARs. Results: BCMA had a restricted RNA expression pattern. Except for expression in plasma cells, BCMA protein was not detected in normal human tissues. BCMA was not detected on primary human CD34+ hematopoietic cells. We detected uniform BCMA cell-surface expression on primary multiple myeloma cells from five of five patients. We designed the first anti-BCMA CARs to be reported and we transduced T cells with lentiviral vectors encoding these CARs. The CARs gave T cells the ability to specifically recognize BCMA. The anti-BCMA-CAR–transduced T cells exhibited BCMA-specific functions including cytokine production, proliferation, cytotoxicity, and in vivo tumor eradication. Importantly, anti-BCMA-CAR–transduced T cells recognized and killed primary multiple myeloma cells. Conclusions: BCMA is a suitable target for CAR-expressing T cells, and adoptive transfer of anti-BCMA-CAR–expressing T cells is a promising new strategy for treating multiple myeloma. Clin Cancer Res; 19(8); 2048–60. ©2013 AACR.
Transcapillary exchange: role and importance of the interstitial fluid pressure and the extracellular matrix
Authors: Rolf K. Reed, Kristofer Rubin
Journal: Cardiovascular Research (2010)

This review will summarize current knowledge on the role of the extracellular matrix (ECM) in general and on the interstitial fluid pressure (Pif) in particular with regard to their importance in transcapillary exchange. The fluid volume in the interstitial space is normally regulated within narrow limits by automatic re-adjustment of the interstitial hydrostatic and colloid osmotic pressures in response to perturbations in capillary filtration and by the lymphatics. Contrary to this commonly accepted view, Pif can become an active force and create a fluid flux across the capillaries in several inflammatory reactions and trauma situations rather than limit the changes occurring. The molecular mechanisms involved in the lowering of Pif include the release of cellular tension exerted on the collagen and microfibril networks in the connective tissue via the collagen-binding β1-integrins, thereby allowing the glycosaminoglycan ground substance, which is normally underhydrated, to expand and take up fluid. Several growth factors and cytokines, including the platelet-derived growth factor BB, are able to reverse a lowering of Pif and restore the normal compaction of the ECM. The magnitude of the lowering of Pif varies with the inflammatory response. In several inflammatory reactions, a lowering of Pif to −5 to −10 mmHg is seen, which will increase capillary filtration by 10–20 times since the normal capillary filtration pressure is usually 0.5–1 mmHg (skin and skeletal muscle). Unless this lowering of Pif is taken into account, the enhanced solute flux resulting from an inflammatory response will be ascribed to an increased capillary permeability.