tbuckley/cabot-search huggingface dataset:
Immunocompetent Cell Functions in Mice Infected With Friend Leukemia Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Michael Bennett, Richard A. Steeves
Journal: JNCI Journal of the National Cancer Institute (1970)

Immunocompetent cell functions were evaluated in mice infected with a preparation of Friend leukemia virus complex (FV) that induces spleen focus formation and polycythemia. FV infection did not impair graft-versus-host reactions, irrespective of whether donor or host mice were infected. Also, alloantigen-sensitive units, which proliferate on exposure to foreign histocompatibility antigens, were not impaired by FV infection. Cells responsible for rejection of hematopoietic allografts in irradiated mice were similarly unaffected. Antigen-sensitive units of lymph nodes responsive to sheep red-blood cell antigens and leading to the formation of hemolytic plaque-forming cells were suppressed by FV infection. The thymic component of antigen-sensitive units, called antigen-reactive cells, was not functionally impaired. However, marrow precursors of plaque-forming cells were markedly suppressed by FV infection. Therefore, FV infection selectively affected precursors of humoral antibody-producing cells. Suppression apparently did not require continued presence of virus, since this effect was detected in infected marrow cell preparations after incubation with Friend antiserum. Immunosuppression was unaffected by previous adrenalectomy, which suggested that the effect was not mediated by adrenal hormones. Cortisol, which also suppresses marrow precursors of plaque-forming cells, enhanced spleen focus formation in susceptible mice. Thus interaction between FV and immunocompetent cells analogous to these precursors was not required for viral induction of erythropoiesis. C57BL/10 mice, genetically refractory to most strains of FV, were not made susceptible to spleen focus formation by prior treatment with cortisol. Therefore, the cellular basis for this genetic refractoriness to FV does not reside in immunocompetent precursors, but probably resides in erythropoietic “target” cells.
The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis
Authors: Camille Roubille, Vincent Richer, Tara Starnino, Collette McCourt, Alexandra McFarlane, Patrick Fleming, Stephanie Siu, John Kraft, Charles Lynde, Janet Pope, Wayne Gulliver, Stephanie Keeling, Jan Dutz, Louis Bessette, Robert Bissonnette, Boulos Haraoui
Journal: Annals of the Rheumatic Diseases (2015)

The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p&lt;0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.
Heterogeneity of the hypoxic state in perfused rat heart.
Authors: C Steenbergen, G Deleeuw, C Barlow, B Chance, J R Williamson
Journal: Circulation Research (1977)

Tissue oxygen gradients were examined in the saline-perfused rat heart by NADH fluorescence photography. In high flow hypoxia, where the coronary flow was maintained and the arterial oxygen tension was gradually reduced, oxygen extraction was virtually complete before oxygen consumption was significantly diminished. Inadequate oxygen delivery resulted in a well defined pattern of anoxic zones. The anoxic zones were several hundred microns in width, an order of magnitude greater than intercapillary distances. In low flow hypoxia (ischemia), where the arterial oxygen tension remained at its control value and the coronary flow was diminished, anoxic zones also developed, following the same pattern as in high flow hypoxia. However, in ischemia, the anoxic areas developed while the effluent oxygen tesion was significantly greater than zero. Whereas respiratory acidosis between pH 7.3 and 6.9 resulted in vasodilation, below PH 6.8 there was a marked increase in vascular resistance. Anoxic zones appeared despite only a slight change in effluent oxygen tension from the control. In high flow hypoxia, ischemia, and acidosis-induced ischemia, the anoxic zones disappeared when control perfusion conditions were restored. The data demonstrate that tissue oxygen gradients are very steep in the hypoxic state, so that ischemia and hypoxia result in discrete heterogeneous areas of anoxic tissue bounded by sharp areas where the oxygen supply is sufficient to maintain normal mitochondrial oxidative function. In these states in which oxygen delivery is less than oxygen demand, coronary perfusion appears to be regulated at the level of the arterioles rather than the capillaries.
Effect of exercise on the nasal transmucosal potential difference in patients with cystic fibrosis and normal subjects.
Authors: S Alsuwaidan, A Li Wan Po, G Morrison, A Redmond, J A Dodge, J McElnay, E Stewart, C F Stanford
Journal: Thorax (1994)

BACKGROUND--Normal subjects have a negative nasal transmucosal potential difference (TPD) at rest which becomes more negative with exercise. Patients with cystic fibrosis have a more negative resting nasal TPD than controls. The present study was designed to determine the effects of exercise on the TPD of patients with cystic fibrosis. METHODS--Seven subjects with cystic fibrosis and seven control subjects had their usual TPD measured at rest, and during and after a 12 minute period on an exercise bicycle designed to produce a pulse rate of 80% of their maximum predicted value. RESULTS--The normal subjects developed a more negative nasal TPD during exercise which returned towards normal at the completion of the rest period. The patients with cystic fibrosis had higher resting values which became less negative during exercise. At the end of the exercise period there was no difference between the two groups. At the end of the recovery period the results for the patients with cystic fibrosis had returned to their resting values. CONCLUSIONS--Exercise reduces the abnormally high resting values for nasal TPD in patients with cystic fibrosis. Elucidation of the mechanism for this change may help to produce functional improvement for patients with this disease.
Psychological Approaches to Origins and Treatments of Somatoform Disorders
Authors: Michael Witthöft, Wolfgang Hiller
Journal: Annual Review of Clinical Psychology (2010)

Medically unexplained symptoms are the defining feature of somatoform disorders (SFD) as currently included in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the International Classification of Diseases, Tenth Edition. Cognitive, behavioral, biological, and social variables are important to our understanding of SFD. Research in the past decade has highlighted the central role of (a) prolonged attention allocation to bodily sensations, (b) the dysfunctional role of catastrophizing symptoms as signs of severe illness, (c) neuroendocrine alterations, and (d) the influence of illness behavior (e.g., the avoidance of physical activity) on the maintenance and chronicity of SFD. Additionally, conditioning approaches have demonstrated that perceiving somatic discomfort can easily be learned. In addition to current models of etiology and pathogenesis, the existing evidence on the efficacy and effectiveness of psychotherapy for SFD is reviewed. Finally, future directions and some current blind spots in research on SFD are outlined.
Treatment Options for Relapsed and Refractory Multiple Myeloma
Authors: Sagar Lonial, Constantine S. Mitsiades, Paul G. Richardson
Journal: Clinical Cancer Research (2011)

Abstract Treatment options for patients with relapsed myeloma have benefited from the development of new targeted agents. The use of bortezomib, thalidomide, and lenalidomide have dramatically changed outcomes for patients with relapsed myeloma. New agents are also in development, on the basis of preclinical rationale, as well as combinations of conventional and novel agents. Together each of these treatment approaches are being tested in phase I, II, and III clinical trials, with the goal of prolonged duration of remission and, ultimately, improved overall survival. Clin Cancer Res; 17(6); 1264–77. ©2011 AACR.
Survivin expression promotes VEGF-induced tumor angiogenesis via PI3K/Akt enhanced β-catenin/Tcf-Lef dependent transcription
Authors: Jaime G Fernández, Diego A Rodríguez, Manuel Valenzuela, Claudia Calderon, Ulises Urzúa, David Munroe, Carlos Rosas, David Lemus, Natalia Díaz, Mathew C Wright, Lisette Leyton, Julio C Tapia, Andrew FG Quest
Journal: Molecular Cancer (2014)

Early in cancer development, tumour cells express vascular endothelial growth factor (VEGF), a secreted molecule that is important in all stages of angiogenesis, an essential process that provides nutrients and oxygen to the nascent tumor and thereby enhances tumor-cell survival and facilitates growth. Survivin, another protein involved in angiogenesis, is strongly expressed in most human cancers, where it promotes tumor survival by reducing apoptosis as well as favoring endothelial cell proliferation and migration. The mechanisms by which cancer cells induce VEGF expression and angiogenesis upon survivin up-regulation remain to be fully established. Since the PI3K/Akt signalling and β-catenin-Tcf/Lef dependent transcription have been implicated in the expression of many cancer-related genes, including survivin and VEGF, we evaluated whether survivin may favor VEGF expression, release from tumor cells and induction of angiogenesis in a PI3K/Akt-β-catenin-Tcf/Lef-dependent manner. Here, we provide evidence linking survivin expression in tumor cells to increased β-catenin protein levels, β-catenin-Tcf/Lef transcriptional activity and expression of several target genes of this pathway, including survivin and VEGF, which accumulates in the culture medium. Alternatively, survivin downregulation reduced β-catenin protein levels and β-catenin-Tcf/Lef transcriptional activity. Also, using inhibitors of PI3K and the expression of dominant negative Akt, we show that survivin acts upstream in an amplification loop to promote VEGF expression. Moreover, survivin knock-down in B16F10 murine melanoma cells diminished the number of blood vessels and reduced VEGF expression in tumors formed in C57BL/6 mice. Finally, in the chick chorioallantoid membrane assay, survivin expression in tumor cells enhanced VEGF liberation and blood vessel formation. Importantly, the presence of neutralizing anti-VEGF antibodies precluded survivin-enhanced angiogenesis in this assay. These findings provide evidence for the existance of a posititve feedback loop connecting survivin expression in tumor cells to PI3K/Akt enhanced β-catenin-Tcf/Lef-dependent transcription followed by secretion of VEGF and angiogenesis.
Bone and cartilage tissue constructs grown using human bone marrow stromal cells, silk scaffolds and rotating bioreactors
Authors: Darja Marolt, Alexander Augst, Lisa E. Freed, Charu Vepari, Robert Fajardo, Nipun Patel, Martha Gray, Michelle Farley, David Kaplan, Gordana Vunjak-Novakovic
Journal: Biomaterials (2006)
Prof. Isabelle Tillie-Leblond
Authors: André-Bernard Tonnel, Benoit Wallaert, Arnaud Scherpereel, Alain Didier, Bruno Housset
Journal: European Respiratory Journal (2013)

We are very sad to announce the passing of Isabelle Tillie-Leblond on March 13, 2013, at the age of 48, after a too-short but intense career. Born to a large family, she was the youngest of seven siblings, and consequently very close to her parents. Her father, a teacher in a private college, was Isabelle’s model and taught his youngest daughter the great principles of life: courage, perseverance and love of others, but also cheerfulness and joie de vivre . Isabelle also knew well a close friend of the Tillie family, Albert Decourtray, a priest who was to become the Cardinal-Archbishop of Lyon; he was her godfather. After her father died, Isabelle kept a close relationship with this eminent Prelate. He remained her valued advisor, always available despite the heavy burden of his work: he always was a confidant and her mentor en humanisme .

Isabelle loved life passionately. She loved her family: her husband David, a radiologist, and her twins Nathan and Francois, whom she admired a lot. One of her qualities was the capacity to throw her whole being (energy, mind and heart) into what she was doing at every moment. It was also true for her patients: …
Bimodal optical diagnostics of oral cancer based on Rose Bengal conjugated gold nanorod platform
Authors: Jia-Hong Wang, Beike Wang, Qian Liu, Qian Li, Hao Huang, Li Song, Tian-Ying Sun, Huaiyu Wang, Xue-Feng Yu, Chengzhang Li, Paul K. Chu
Journal: Biomaterials (2013)
Retrospective Multicenter Study in Non Small Cell Lung Cancer (Nsclc) Patients with Epidermal Growth Factor Receptor (Egfr) Activating Mutation Treated First-Line Tyrosine Kinase Inhibitor (Tki): Evaluation of Progression According to Recist, Therapeutic Approach and Its Effect
Authors: J.B. Auliac, C. Fournier, C. Audigier Valette, M. Perol, A. Bizieux, I. Monnet, C. croisette Phan De van Ho, S. Bota Ouchlif, R. Corre, G. Le Garff, P. Fournel, N. Baize, R. Lamy, A. Vergnenegre, D. Arpin, B. Marin, L. Greillier, R. Gervais
Journal: Annals of Oncology (2014)
An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane.
Authors: M W Wakelin, M J Sanz, A Dewar, S M Albelda, S W Larkin, N Boughton-Smith, T J Williams, S Nourshargh
Journal: The Journal of Experimental Medicine (1996)

Platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) plays an active role in the process of leukocyte migration through cultured endothelial cells in vitro and anti-PECAM-1 antibodies (Abs) inhibit accumulation of leukocytes into sites of inflammation in vivo. Despite the latter, it is still not clear at which stage of leukocyte emigration in vivo PECAM-1 is involved. To address this point directly, we studied the effect of an anti-PECAM-1 Ab, recognizing rat PECAM-1, on leukocyte responses within rat mesenteric microvessels using intravital microscopy. In mesenteric preparations activated by interleukin (IL)-1 beta, the anti-PECAM-1 Ab had no significant effect on the rolling or adhesion of leukocytes, but inhibited their migration into the surrounding extravascular tissue in a dose-dependent manner. Although in some vessel segments these leukocytes had come to a halt within the vascular lumen, often the leukocytes appeared to be trapped within the vessel wall. Analysis of these sections by electron microscopy revealed that the leukocytes had passed through endothelial cell junctions but not the basement membrane. In contrast to the effect of the Ab in mesenteric preparations treated with IL-1 beta, leukocyte extravasation induced by topical or intraperitoneal administration of the chemotactic peptide formyl-methionyl-leucyl-phenylalanine was not inhibited by the anti-PECAM-1 Ab. These results directly demonstrate a role for PECAM-1 in leukocyte extravasation in vivo and indicate that this involvement is selective for leukocyte extravasation elicited by certain inflammatory mediators. Further, our findings provide the first in vivo indication that PECAM-1 may have an important role in triggering the passage of leukocytes through the perivascular basement membrane.
Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden
Authors: P. Raaschou, J. F. Simard, M. Holmqvist, J. Askling
Journal: BMJ (2013)

<b>Objectives</b> To investigate the potential association between tumour necrosis factor (TNF) inhibitor treatment and malignant melanomas in rheumatoid arthritis, melanoma risks in rheumatoid arthritis patients not treated with biological drugs, and risk of all site cancer with TNF inhibitors as used in rheumatoid arthritis. <b>Design</b> Population based cohort study. <b>Setting</b> Prospectively recorded data from national clinical, health, and demographic registers in Sweden 2001-10. Patients with rheumatoid arthritis treated (n=10 878) or not (n=42 198) with TNF inhibitors and matched general population comparators (n=162 743). <b>Main outcome measures</b> The primary outcome was first invasive melanoma in people without any history of invasive cancer of any type. Hazard ratios were estimated using Cox regression, comparing non-biological drug treated rheumatoid arthritis patients with the general population comparator and TNF inhibitor treated rheumatoid arthritis patients with those not treated with biological drugs. Secondary outcomes included in situ melanomas, second primary melanomas, and all site cancer. <b>Results</b> 113 first invasive melanomas occurred in rheumatoid arthritis patients not treated with biological drugs, and 393 occurred in the general population comparator cohort. Rheumatoid arthritis patients not treated with biological drugs were not at significantly increased risk of melanoma compared with the general population (hazard ratio 1.2, 95% confidence interval 0.9 to 1.5). 38 first invasive melanomas occurred in rheumatoid arthritis patients treated with TNF inhibitors; these patients had an increased risk of melanoma compared with rheumatoid arthritis patients not treated with biological drugs (hazard ratio 1.5, 1.0 to 2.2; 20 additional cases per 100 000 person years). The risk of a second primary melanoma was non-significantly increased (hazard ratio 3.2, 0.8 to 13.1; n=3 <i>v</i> 10) in rheumatoid arthritis patients treated with TNF inhibitors compared with those not treated with biological drugs. <b>Conclusion</b> Overall, patients with rheumatoid arthritis who have not been treated with biological drugs are not at increased risk of invasive melanoma compared with the general population. Rheumatoid arthritis patients selected for TNF inhibitor treatment are not at increased overall risk for cancer but have a 50% increased relative risk of invasive melanoma. Given the small increase in absolute risk, these finding may not markedly shift the overall risk-benefit balance of TNF inhibitors as used in clinical practice but might do so in patients at high risk of melanoma for other reasons.
Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer
Authors: Raju R Raval, Andrew B Sharabi, Amanda J Walker, Charles G Drake, Padmanee Sharma
Journal: Journal for ImmunoTherapy of Cancer (2014)

Knowledge of the basic mechanisms of the immune system as it relates to cancer has been increasing rapidly. These developments have accelerated the translation of these advancements into medical breakthroughs for many cancer patients. The immune system is designed to discriminate between self and non-self, and through genetic recombination there is virtually no limit to the number of antigens it can recognize. Thus, mutational events, translocations, and other genetic abnormalities within cancer cells may be distinguished as "altered-self" and these differences may play an important role in preventing the development or progression of cancer. However, tumors may utilize a variety of mechanisms to evade the immune system as well. Cancer biologists are aiming to both better understand the relationship between tumors and the normal immune system, and to look for ways to alter the playing field for cancer immunotherapy. Summarized in this review are discussions from the 2013 SITC Primer, which focused on reviewing current knowledge and future directions of research related to tumor immunology and cancer immunotherapy, including sessions on innate immunity, adaptive immunity, therapeutic approaches (dendritic cells, adoptive T cell therapy, anti-tumor antibodies, cancer vaccines, and immune checkpoint blockade), challenges to driving an anti-tumor immune response, monitoring immune responses, and the future of immunotherapy clinical trial design.
Fiber Implantation for Pattern Baldness
Authors: C. William Hanke
Journal: JAMA (1979)

Examination of 20 patients who had fiber implantation for the treatment of pattern baldness showed that nearly all the fibers had fallen out by ten weeks. Complications observed were facial swelling, infection, foreign-body granulomas, scarring, and permanent hair loss. Scanning electron microscopy identified the fibers as modacrylic fibers. The complications, high monetary cost, and ultimate futility of fiber implantation make it an unacceptable procedure. (<i>JAMA</i>241:146-148, 1979)
Tetrahydrobiopterin-dependent preservation of nitric oxide–mediated endothelial function in diabetes by targeted transgenic GTP–cyclohydrolase I overexpression
Authors: Nicholas J. Alp, Shafi Mussa, Jeffrey Khoo, Shijie Cai, Tomasz Guzik, Andrew Jefferson, Nicky Goh, Kirk A. Rockett, Keith M. Channon
Journal: Journal of Clinical Investigation (2003)

Increased production of reactive oxygen species and loss of endothelial NO bioactivity are key features of vascular disease states such as diabetes mellitus. Tetrahydrobiopterin (BH4) is a required cofactor for eNOS activity; pharmacologic studies suggest that BH4 may mediate some of the adverse effects of diabetes on eNOS function. We have now investigated the importance and mechanisms of BH4 availability in vivo using a novel transgenic mouse model with endothelial-targeted overexpression of the rate-limiting enzyme in BH4 synthesis, guanosine triphosphate–cyclohydrolase I (GTPCH). Transgenic (GCH-Tg) mice demonstrated selective augmentation of endothelial BH4 levels. In WT mice, induction of diabetes with streptozotocin (STZ) increased vascular oxidative stress, resulting in oxidative loss of BH4, forming BH2 and biopterin. Endothelial cell superoxide production in diabetes was increased, and NO-mediated endothelium-dependent vasodilatation was impaired. In diabetic GCH-Tg mice, superoxide production from the endothelium was markedly reduced compared with that of WT mice, endothelial BH4 levels were maintained despite some oxidative loss of BH4, and NO-mediated vasodilatation was preserved. These findings indicate that BH4 is an important mediator of eNOS regulation in diabetes and is a rational therapeutic target to restore NO-mediated endothelial function in diabetes and other vascular disease states.