tbuckley/cabot-search huggingface dataset:
Glycosylated Serum Albumin: An Intermediate Index of Diabetic Control
Authors: Ian R Jones, David R Owens, Sheila Williams, Robert E J Ryder, Anthony J Birtwell, Martin K Jones, Kimani Gicheru, Tom M Hayes
Journal: Diabetes Care (1983)

Glycosylated hemoglobin (HbA1) is widely used as an index of glycemic control in diabetic patients. However, due to the long survival time of erythrocytes (120 days), it remains elevated for several weeks after improved control. Other plasma proteins are similarly glycosylated, and as glycosylated serum albumin (GSA) has a shorter half-life (20 days), it should detect glycemic changes earlier. Fasting blood glucose (FBG), GSA, and HbA1 were measured weekly in newly diagnosed diabetic patients (N = 12) for 8 wk after beginning treatment. After 4 wk, a similar fall in FBG and GSA levels, i.e., 72% and 58% respectively, was observed. In contrast, HbA1 fell significantly less (P &amp;lt; 0.01), by only 39% of its initial value. By 8 wk there was no significant difference between the percentage reduction in the three indices of control. Therefore, GSA provides the clinician with earlier objective evidence of the metabolic response to therapeutic intervention and can be regarded as an intermediate index of diabetic control.
Inhibition of Src Family Kinases and Receptor Tyrosine Kinases by Dasatinib: Possible Combinations in Solid Tumors
Authors: Juan Carlos Montero, Samuel Seoane, Alberto Ocaña, Atanasio Pandiella
Journal: Clinical Cancer Research (2011)

Abstract Dasatinib is a small molecule tyrosine kinase inhibitor that targets a wide variety of tyrosine kinases implicated in the pathophysiology of several neoplasias. Among the most sensitive dasatinib targets are ABL, the SRC family kinases (SRC, LCK, HCK, FYN, YES, FGR, BLK, LYN, and FRK), and the receptor tyrosine kinases c-KIT, platelet-derived growth factor receptor (PDGFR) α and β, discoidin domain receptor 1 (DDR1), c-FMS, and ephrin receptors. Dasatinib inhibits cell duplication, migration, and invasion, and it triggers apoptosis of tumoral cells. As a consequence, dasatinib reduces tumoral mass and decreases the metastatic dissemination of tumoral cells. Dasatinib also acts on the tumoral microenvironment, which is particularly important in the bone, where dasatinib inhibits osteoclastic activity and favors osteogenesis, exerting a bone-protecting effect. Several preclinical studies have shown that dasatinib potentiates the antitumoral action of various drugs used in the oncology clinic, paving the way for the initiation of clinical trials of dasatinib in combination with standard-of-care treatments for the therapy of various neoplasias. Trials using combinations of dasatinib with ErbB/HER receptor antagonists are being explored in breast, head and neck, and colorectal cancers. In hormone receptor–positive breast cancer, trials using combinations of dasatinib with antihormonal therapies are ongoing. Dasatinib combinations with chemotherapeutic agents are also under development in prostate cancer (dasatinib plus docetaxel), melanoma (dasatinib plus dacarbazine), and colorectal cancer (dasatinib plus oxaliplatin plus capecitabine). Here, we review the preclinical evidence that supports the use of dasatinib in combination for the treatment of solid tumors and describe various clinical trials developed following a preclinical rationale. Clin Cancer Res; 17(17); 5546–52. ©2011 AACR.
Use of BCG as an immunostimulant in the surgical treatment of carcinoma of the lung
Authors: F. R. Edwards, F. Whitwell
Journal: Thorax (1974)

<b>Edwards, F. R. and Whitwell, F. (1974).</b><i>Thorax</i>, <b>29</b>, 654-658. <b>Use of BCG as an immunostimulant in the surgical treatment of carcinoma of the lung.</b> Cell-mediated immunity to cancer cells would appear to exert some control over the extension of tumour growth, and stimulation of this factor might result in increased survival after surgical treatment of the tumour. Of the various agents used as stimulators in experimental work, BCG would seem to be the most convenient to use in man. A single dose of BCG-Glaxo (500,000 organisms) was given subdermally 10 days after excision of lung carcinoma. The length of survival was used as the index of the effect of the BCG. Two trials were initiated, the first to study the safety of BCG and a survival study of 120 consecutive cases (60 used as controls). This is an interim report at two years of this trial. The main features at this stage show that the overall survival rate has increased from 38% in the controls to 52% in the BCG group. In the squamous-cell group survival has risen from 50% to 62% and, in those with positive nodes, from 33% to 53%. In the oat-cell group, two-year survival has risen from 11% in the controls to 50% in the BCG groups, though the numbers are small. Although encouraging, the results are not statistically significant. The second trial is a randomized trial in which five surgeons have taken part, and 500 consecutive cases of lung resection for carcinoma are documented (250 control and 250 BCG). It is too early for results to be assessed in this group. It is hoped that at three, four, and five years more favourable survival figures will be obtained.
The Brain's Default Mode Network
Authors: Marcus E. Raichle
Journal: Annual Review of Neuroscience (2015)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its discovery was an unexpected consequence of brain-imaging studies first performed with positron emission tomography in which various novel, attention-demanding, and non-self-referential tasks were compared with quiet repose either with eyes closed or with simple visual fixation. The default mode network consistently decreases its activity when compared with activity during these relaxed nontask states. The discovery of the default mode network reignited a longstanding interest in the significance of the brain's ongoing or intrinsic activity. Presently, studies of the brain's intrinsic activity, popularly referred to as resting-state studies, have come to play a major role in studies of the human brain in health and disease. The brain's default mode network plays a central role in this work.
Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301)
Authors: L. Dahan, F. Bonnetain, M. Ychou, E. Mitry, M. Gasmi, J.-L. Raoul, S. Cattan, J.-M. Phelip, P. Hammel, B. Chauffert, P. Michel, J.-L. Legoux, P. Rougier, L. Bedenne, J.-F. Seitz
Journal: Gut (2010)

<h3>Purpose</h3> Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma. Although the 5-fluorouracil (5FU), folinic acid and cisplatin combination (LV5FU2-CDDP) is an option, the optimal order of the regimens must be determined. The first strategic phase III trial comparing LV5FU2-CDDP followed by gemcitabine versus gemcitabine followed by LV5FU2-CDDP was conducted. <h3>Methods</h3> Patients with metastatic pancreatic adenocarcinoma, performance status (PS) 0–2, without prior chemotherapy were randomly assigned (1:1) to receive either LV5FU2-CDDP followed by gemcitabine at disease progression or toxicity (Arm A), or the opposite sequence (Arm B). 202 patients had to be included and 170 deaths had to be observed to detect an expected improvement in median overall survival (OS) from 6.5 to 10 months in Arm A (two-sided α = 5% and β = 20%). <h3>Results</h3> 202 patients were included (Arm A, 102; Arm B, 100). Median age, male/female ratio, PS 0–1 and previous surgery were similar in the two arms. After a median follow-up of 44 months, median OS in Arm A was 6.6 months versus 8.0 months in Arm B (p = 0.85). Median progression-free survival was similar between Arms A and B. More grade 3/4 toxicities were observed when LV5FU2-CDDP was administered as a first-line treatment compared with gemcitabine: 79% versus 64% (p = 0.018). <h3>Conclusion</h3> This trial did not show any strategic advantage to using LV5FU2-CDDP as a first-line treatment and suggests that gemcitabine remains the standard first-line treatment. Sixty-one per cent of patients were able to receive a second line of chemotherapy.
Synergistic Induction of Adaptive Antitumor Immunity by Codelivery of Antigen with α-Galactosylceramide on Exosomes
Authors: Ulf Gehrmann, Stefanie Hiltbrunner, Anna-Maria Georgoudaki, Mikael C. Karlsson, Tanja I. Näslund, Susanne Gabrielsson
Journal: Cancer Research (2013)

Abstract Exosomes and the invariant NKT (iNKT) immune cell ligand α-galactosylceramide (αGC) may offer novel tools for cancer immunotherapy. In this study, we investigated whether exosomes loaded with αGC can activate iNKT cells and potentiate a cancer-specific adaptive immune response. αGC loaded exosomes readily activated iNKT cells both in vitro and in vivo. Exosomes loaded with αGC plus the model antigen ovalbumin (OVA) induced potent NK and γδ T-cell innate immune responses, and they also synergistically amplified T- and B-cell responses that were OVA specific. In contrast to soluble αGC, which anergizes iNKT cells, we found that αGC/OVA-loaded exosomes did not induce iNKT cell anergy but were more potent than soluble αGC + OVA in inducing adaptive immune responses. In an OVA-expressing mouse model of melanoma, treatment of tumor-bearing mice with αGC/OVA-loaded exosomes decreased tumor growth, increased antigen-specific CD8+ T-cell tumor infiltration, and increased median survival, relative to control mice immunized with soluble αGC + OVA alone. Notably, an additional injection of αGC/OVA-loaded exosomes further augmented the treatment effects. Our findings show that exosomes loaded with protein antigen and αGC will activate adaptive immunity in the absence of triggering iNKT-cell anergy, supporting their application in the design of a broad variety of cancer immunotherapy trials. Cancer Res; 73(13); 3865–76. ©2013 AACR.
Chemical and hard metal induced exogenous toxic alveolitis (ETA) (follow up 1,5 years)
Authors: Galina Orlova, Anatoliy Lavrushin
Journal: European Respiratory Journal (2013)

Aim. To study the prognostic criteria for ETA.

Methods. 44 patients with ETA, mean age 39,3±1,2 yrs were examined during 0,5-1-1,5 yrs. 77 % of patients were exposed to chemicals for 17,5±3,5 yrs, 23 % of patients - to hard metals for 11,4±3,6 yrs. X-ray, computer tomography (CT), complex lung function examination, were performed. All patients received prednisolone and plasmapheresis courses. The diagnosis was verified histologically by lung biopsy in 30 cases. Blood neutrophil phagocytic activity, spontaneous chemiluminescence (SpCl) and stimulated by formil peptide chemiluminescence (StCl) of blood neutrophils, BALF antioxidant activity (AOA) were examined.

Results. The clinical and CT improvement was observed in 31 (70%) patients; stabilization of clinical status - in 7 (16 %) and deterioration – in 6 (14 %) patients. The analysis of X2 criteria, Kramer coefficient (C) confirmed the close connection of CT signs aggravation with exposure duration (X2 =181,6; p<0,05; C=1,0). The significant (p<0,05) gradient of increasing VC, FEV1, DLCO was noted after 1 yr. of treatment. Morphological signs (neutrophil, lymphocyte infiltration, granuloma formation,) correlated with neutrophil phagocytic activity: r=0,47; p<0,05 for phagocyte number; r=0,5; p<0,05 for phagocyte index. CT signs of “ground glass”, infiltration correlated with decreased BALF AOA (r=-0,74) and “honeycombing” - with increased SpCl (r=1,0), StCl (r=0,9); p<0,05 for all parameters.

Conclusion. Protracted exposure to harmful factors, oxidative activity of blood neutrophils associated with decreased BALF AOA are poor prognostic criteria for ETA. Systemic steroids and plasmapheresis is the pathogenic therapy of this disease.
CpG Blocks Immunosuppression by Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice
Authors: Christine Zoglmeier, Helen Bauer, Daniel Nörenberg, Georg Wedekind, Philipp Bittner, Nadja Sandholzer, Moritz Rapp, David Anz, Stefan Endres, Carole Bourquin
Journal: Clinical Cancer Research (2011)

The Toll-like receptor (TLR) 9 ligand CpG has been used successfully for the immunotherapy of cancer. Chronic CpG application in tumor-free hosts leads, however, to the expansion of myeloid-derived suppressor cells (MDSC), which can cause T-cell suppression and may thus hamper the development of an effective immune response. Here, we investigated the effect of TLR9 activation on the function of MDSC in tumor-bearing mice.We investigated the effect of CpG treatment on the number, phenotype, and function of MDSC in mice bearing subcutaneous C26 tumors and in CEA424-TAg mice bearing autochthonous gastric tumors.CpG treatment blocks the suppressive activity of MDSC on T-cell proliferation in both tumor models. Inhibition of MDSC function by CpG was particularly pronounced for a highly suppressive Ly6G(hi) polymorphonuclear subset of MDSC. We further show that TLR9 activation by CpG promotes maturation and differentiation of MDSC and strongly decreases the proportion of Ly6G(hi) MDSC in both tumor-bearing and tumor-free mice. We demonstrate that IFN-α produced by plasmacytoid dendritic cells upon CpG stimulation is a key effector for the induction of MDSC maturation in vitro and show that treatment of mice with recombinant IFN-α is sufficient to block MDSC suppressivity.We show here for the first time that TLR9 activation inhibits the regulatory function of MDSC in tumor-bearing mice and define a role for the antitumoral cytokine IFN-α in this process.
Functional tissue-engineered blood vessels from bone marrow progenitor cells
Authors: J LIU, D SWARTZ, H PENG, S GUGINO, J RUSSELL, S ANDREADIS
Journal: Cardiovascular Research (2007)

Stem cells have significant potential for development of cell-based therapeutics for cardiovascular tissue regeneration.We developed a novel method for isolating smooth muscle cells (SMC) from ovine bone marrow using a tissue-specific promoter and fluorescence-activated cell sorting.As compared to vascular SMC, bone marrow-derived smooth muscle progenitor cells (BM-SMPC) exhibited similar morphology, showed higher proliferation potential and expressed several SMC markers including alpha-actin, calponin, myosin heavy chain, smoothelin, caldesmon and SM22. When embedded in fibrin hydrogels, BM-SMPC contracted the matrix and displayed receptor- and non-receptor-mediated contractility, indicating that BM-SMPC can generate force in response to vasoreactive agonists. We also prepared tissue-engineered blood vessels from BM-SMPC and BM-derived endothelial cells and implanted them into the jugular veins of lambs. As early as five weeks post-implantation, grafted tissues displayed a confluent endothelial layer overlaying the medial layer in which BM-SMPC were aligned circumferentially and synthesized significant amounts of collagen. In contrast to previous results with vascular SMC, BM-SMPC synthesized high amounts of elastin that was organized in a fibrillar network very similar to that of native vessels.Our results suggest that BM-SMPC may be useful in studying SMC differentiation and have high potential for development of cell therapies for the treatment of cardiovascular disease.
GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO
Authors: Judith A. Kapp, Carl W. Pierce, Stuart Schlossman, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1974)

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-theta serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained theta-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.
5-Methyltetrahydrofolate for biochemical modulation of fluorouracil (FU) in patients with advanced colorectal cancer: A randomized phase I–II study of two different FU administration schedules
Authors: M. Hejna, G.V. Kornek, M. Raderer, J. Valencak, G. Weinländer, W. Fiebiger, J. Miholic, W. Scheithauer
Journal: Annals of Oncology (1998)
Decreased TNF-α synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging
Authors: Elaine Agius, Katie E. Lacy, Milica Vukmanovic-Stejic, Ann L. Jagger, Anna-Pia Papageorgiou, Sue Hall, John R. Reed, S. John Curnow, Judilyn Fuentes-Duculan, Christopher D. Buckley, Mike Salmon, Leonie S. Taams, James Krueger, John Greenwood, Nigel Klein, Malcolm H.A. Rustin, Arne N. Akbar
Journal: The Journal of Experimental Medicine (2009)

Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4+ T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-α secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-α after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging.
Reproductive Toxicity of Environmental Agents
Authors: K. S. Rao, B. A. Schwetz
Journal: Annual Review of Public Health (1982)

Reproductive processes may be affected adversely by exposure to certain levels of environmental agents, in both animals and humans. It is not only exposure during pregnancy itself that may be hazardous, but exposure of males and females to some environmental agents at any time may cause changes in the germ cells; this can result in infertility or an adverse outcome for a subsequent conceptus. For perspective, it must be emphasized that there is no indication that most reproductive difficulties are associated with chemicals of any sort. However, some chemicals can interfere with repro­ duction if humans or animals are exposed to large enough concentrations over a prolonged period of time. Therefore, it is important that such effects . be understood and the causative conditions avoided. Of the injury to the reproduction of man and domestic animals that can be traced to chemicals, almost all is somatic, including injury to the embryo leading to the produc­ tion of deformed young. We do not consider here agents that induce repro­ ductive effects via teratogenesis; we refer the reader to extensive volumes by Wilson & Fraser (1). Reproductive effects can also be induced by modu­ lation of the genotype in the germ cells, namely mutations and clastogenesis (chromosome damage). Although agents that induce mutations and clasto­ genesis have been identified in laboratory studies, such an effect has not hitherto been demonstrated in humans. It is not the purpose of this review to catalogue all such agents; rather, we refer the reader to Fishbein (2). Our objective in this essay is to present an overall view of the reproductive toxic potential of various classes of chemicals. Obviously, a discussion of such a broad topic as reproductive toxicity requires selectivity. We used the following guidelines:
The accuracy and reliability of commercial heart rate monitors.
Authors: M J Burke, M V Whelan
Journal: British Journal of Sports Medicine (1987)

In recent years increasing emphasis has been placed on the benefits of exercise to normal healthy adults as well as to those recovering from heart attacks and other illnesses. As an aid to exercise training many portable heart-rate monitors have been placed on the market but little appears to have been done to assess the performance of these machines. The authors have examined the performance of four such monitors both under bench-test and practical exercising conditions. When tested on the bench using electronic equipment, the machines rarely exhibited errors exceeding 2-3 bpm over a measurement range of 30-240 bpm. However, when tested with subjects walking or jogging at low speeds on a treadmill, typically 20-70% of the readings given by the machines had errors of greater than 20 bpm. In some cases over 50% of readings had errors exceeding 50 bpm.
Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women
Authors: Maria Creatsa, Eleni Armeni, Kimon Stamatelopoulos, Demetrios Rizos, Georgios Georgiopoulos, Maria Kazani, Andreas Alexandrou, Spyridon Dendrinos, Areti Augoulea, Christos Papamichael, Irene Lambrinoudaki
Journal: Metabolism (2011)
Proline-, Glutamic Acid-, and Leucine-Rich Protein-1 Is Essential in Growth Factor Regulation of Signal Transducers and Activators of Transcription 3 Activation
Authors: Bramanandam Manavathi, Sujit S. Nair, Rui-An Wang, Rakesh Kumar, Ratna K. Vadlamudi
Journal: Cancer Research (2005)

Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1) is a novel estrogen receptor coactivator that plays an important role in the genomic and nongenomic actions of estrogen receptor by interacting with histones and src-mitogen-activated protein kinase pathway, respectively. A great deal of information has emerged in recent years about the possible role of PELP1 in estrogen receptor signaling. However, the participation and significance of PELP1 in other cellular signaling pathways remains unknown. Using a yeast two-hybrid screen, we identified PELP1 as a novel interacting protein of signal transducers and activators of transcription 3 (STAT3) and found evidence of physiologic interaction between PELP1 and STAT3. We also found that these interactions played a mechanistic role in the positive regulation of STAT3 transcription from synthetic promoters and endogenous target genes such as cyclin D1, c-myc, and c-fos. Overexpression of PELP1 enhanced phosphorylation of STAT3 at Ser727 in a src-mitogen-activated protein kinase-sensitive manner and, conversely, down-regulation of PELP1 compromised growth factor-mediated induction of STAT3 target genes. We also discovered that PELP1 interacts with STAT3 in the nuclear compartment and down-regulation of PELP1 interfered with the recruitment of STAT3 to its target gene promoters. In summary, our results highlight a novel role for PELP1 in growth factor signaling and indicate that PELP1-mediated genomic and nongenomic functions play a role in the growth factor-mediated STAT3 transactivation functions. Such regulatory interactions of PELP1 may have important functional implications in the cross-talk of estrogen receptor and growth factor signaling.