tbuckley/cabot-search huggingface dataset:
Fibroblast chemotaxis induction by human recombinant interleukin-4. Identification by synthetic peptide analysis of two chemotactic domains residing in amino acid sequences 70-88 and 89-122.
Authors: A E Postlethwaite, J M Seyer
Journal: Journal of Clinical Investigation (1991)

Interleukin-4 is a T lymphocyte- and mast cell-derived cytokine with pleiotropic properties with biological effects on a variety of target cells including B and T lymphocytes, macrophages, hematopoietic cells, mast cells, and fibroblasts. In addition to the proliferation effect of IL-4 on fibroblasts, which has been previously described, in this report the chemotactic properties of IL-4 for fibroblasts is described. Human recombinant IL-4 induced the chemotactic migration of dermal fibroblasts in vitro in modified Boyden-type chambers at concentrations between 10(-12) and 10(-11) M. The chemotactic activity of IL-4 was neutralized by anti-human recombinant IL-4 IgG antibodies. Oligopeptides representing the complete deduced amino acid sequence of human IL-4 were synthesized by the Merrifield technique and tested for their ability to induce fibroblast chemotaxis. Two peptides representing residues 70-88 and 89-122 induced fibroblast migration. Peptide 70-88 was the more potent of the two causing chemotaxis of fibroblasts at 10(-8)-10(-6) M while peptide 89-129 induced migration at 10(-7)-10(-5) M. Although the mechanism by which IL-4 and these two peptides induce fibroblast chemotaxis is unknown, each of these three compounds were able to chemotactically desensitize fibroblasts to the chemotactic effects of the other two but not to a structurally unrelated chemotactic cytokine, transforming growth factor beta-1. These studies suggest that IL-4 might function in vivo to induce the accumulation of fibroblasts at sites of tissue injury, inflammatory and immune reactions in which T lymphocytes and mast cells participate.
Current Evidence Base for Use of the Implantable Cardioverter–Defibrillator
Authors: Stefan H. Hohnloser, Carsten W. Israel
Journal: Circulation (2013)

Evidence Base for ICD Therapy 173arrhythmic mortality was reduced by the ICD, an unexpected increase in death from other causes offset this effect and caused the study to be neutral.A similar phenomenon was seen in 2 other more recent trials, the Defibrillator IN Acute Myocardial Infarction Trial (DINAMIT) and the Immediate Risk-Stratification Improves Survival (IRIS) studies that enrolled patients early after an acute MI. 14,16 In both trials, the benefit of the ICD in reducing arrhythmic death was counterbalanced by excess mortality from nonarrhythmic causes. Primary Prevention Trials in Patients With Nonischemic CardiomyopathyThe largest prospective study of exclusively nonischemic patients was the Defibrillator In Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, 13 which randomly assigned 458 patients with a LVEF ≤35% and nonsustained VT to medical therapy or the ICD.The primary end point of all-cause mortality did not reach statistical significance (2-year mortality 14% versus 8%, P=0.08).
Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case–control study
Authors: Thomas N Williams, Sophie Uyoga, Alex Macharia, Carolyne Ndila, Charlotte F McAuley, Daniel H Opi, Salim Mwarumba, Julie Makani, Albert Komba, Moses N Ndiritu, Shahnaaz K Sharif, Kevin Marsh, James A Berkley, J Anthony G Scott
Journal: The Lancet (2009)
Trans-nodal migration of resident dendritic cells into medullary interfollicular regions initiates immunity to influenza vaccine
Authors: Matthew C. Woodruff, Balthasar A. Heesters, Caroline N. Herndon, Joanna R. Groom, Paul G. Thomas, Andrew D. Luster, Shannon J. Turley, Michael C. Carroll
Journal: The Journal of Experimental Medicine (2014)

Dendritic cells (DCs) are well established as potent antigen-presenting cells critical to adaptive immunity. In vaccination approaches, appropriately stimulating lymph node–resident DCs (LNDCs) is highly relevant to effective immunization. Although LNDCs have been implicated in immune response, their ability to directly drive effective immunity to lymph-borne antigen remains unclear. Using an inactive influenza vaccine model and whole node imaging approaches, we observed surprising responsiveness of LNDC populations to vaccine arrival resulting in a transnodal repositioning into specific antigen collection sites within minutes after immunization. Once there, LNDCs acquired viral antigen and initiated activation of viral specific CD4+ T cells, resulting in germinal center formation and B cell memory in the absence of skin migratory DCs. Together, these results demonstrate an unexpected stimulatory role for LNDCs where they are capable of rapidly locating viral antigen, driving early activation of T cell populations, and independently establishing functional immune response.
Protein Overload Induces Fractalkine Upregulation in Proximal Tubular Cells through Nuclear Factor κB– and p38 Mitogen-Activated Protein Kinase–Dependent Pathways
Authors: Roberta Donadelli, Cristina Zanchi, Marina Morigi, Simona Buelli, Cristian Batani, Susanna Tomasoni, Daniela Corna, Daniela Rottoli, Ariela Benigni, Mauro Abbate, Giuseppe Remuzzi, Carla Zoja
Journal: Journal of the American Society of Nephrology (2003)

Investigated was the effect of high albumin concentrations on proximal tubular cell expression of fractalkine. Human proximal tubular cells (HK-2) were incubated with human serum albumin (HSA), which induced a dose-dependent increase in fractalkine mRNA associated with increased levels of both membrane-bound and soluble forms of the protein. To evaluate the role of nuclear factor kappaB (NF-kappaB) activation in HSA-induced fractalkine mRNA, HK-2 cells were infected with a recombinant adenovirus encoding the natural inhibitor of NF-kappaB, IkBalpha; a 43% reduction of fractalkine mRNA levels resulted. Similarly, when cells were infected with the recombinant adenovirus expressing dominant negative mutant of the IkB kinase 2, a 55% inhibition of fractalkine mRNA was achieved. p38 mitogen-activated protein kinase was activated by HSA and was involved in NF-kappaB-dependent transcription of fractalkine. In kidneys of mice with bovine serum albumin overload proteinuria, fractalkine mRNA levels were 2.3-fold greater than those of controls. Fractalkine expression was also induced in tubular epithelial cells in this model. Anti-CXCR1 antibody treatment limited interstitial accumulation of mononuclear cells. Protein overload is a promoter of fractalkine gene induction mediated by NF-kappaB and p38 activation in proximal tubular cells. Fractalkine might contribute to direct mononuclear cells into peritubular interstitium and enhance their adhesion property, which in turn would favor inflammation and disease progression.
Vaccine-induced hepatitis B surface antigen positivity in adult hemodialysis patients
Authors: L Janzen, G Y Minuk, M Fast, K N Bernstein
Journal: Journal of the American Society of Nephrology (1996)

This report describes hepatitis B vaccinations that resulted in transient hepatitis B surface antigen positivity in six adult hemodialysis patients. Initially, three patients were incidentally discovered to be hepatitis B surface antigen-positive temporally related to hepatitis B vaccination. Two other patients who displayed transient positivity were among 15 hemodialysis patients under prospective surveillance after receiving a dose of hepatitis B vaccine. The sixth patient was negative for hepatitis B surface antigen when monitored in the prospective surveillance group but was incidentally found to be positive after a nonsurveillance dose of the vaccine. All positive cases cleared hepatitis B surface antigen within 20 days of vaccination. In our search of the literature, this is the first report of hepatitis B vaccine inducing hepatitis B surface antigen positivity in adult hemodialysis patients. Because this study proposes that this transient surface antigen positivity is vaccine-induced and not a true hepatitis B infection, we recommend that renal dialysis patients not be screened for hepatitis B surface antigen for at least 21 to 28 days after hepatitis B vaccination. As well, blood donors should not donate blood in this early postvaccination period. These guidelines would incorporate a measure of safety to prevent individuals in the early postinoculation period from being erroneously labeled as having hepatitis B viral infections.
EphB3 Is Overexpressed in Non–Small-Cell Lung Cancer and Promotes Tumor Metastasis by Enhancing Cell Survival and Migration
Authors: Xiao-Dan Ji, Guo Li, Yu-Xiong Feng, Jiang-Sha Zhao, Jing-Jing Li, Zhi-Jian Sun, Shuo Shi, Yue-Zhen Deng, Jun-Feng Xu, Yin-Qiu Zhu, H. Phillip Koeffler, Xiang-Jun Tong, Dong Xie
Journal: Cancer Research (2011)

Abstract Eph receptors, the largest subfamily of transmembrane tyrosine kinase receptors, have been increasingly implicated in various physiologic and pathologic processes, and the roles of the Eph family members during tumorigenesis have recently attracted growing attention. Until now, research on EphB3 function in cancer is limited to focusing on tumor suppression by EphB receptors in colorectal cancer. However, its function in other types of cancer remains poorly investigated. In this study, we explored the function of EphB3 in non–small-cell lung cancer (NSCLC). We found that the expression of EphB3 was significantly upregulated in clinical samples and cell lines, and the expression level correlated with the patient pathologic characteristics, including tumor size, differentiation, and metastasis. Overexpression of EphB3 in NSCLC cell lines accelerated cell growth and migration and promoted tumorigenicity in xenografts in a kinase-independent manner. In contrast, downregulation of EphB3 inhibited cell proliferation and migration and suppressed in vivo tumor growth and metastasis. Furthermore, we showed that silencing of EphB3 inhibited cell growth by reducing DNA synthesis and caspase-8–mediated apoptosis and suppressed cell migration by increasing accumulation of focal adhesion formation. Taken together, our findings suggest that EphB3 provides critical support to the development and progression of NSCLC by stimulating cell growth, migration, and survival, thereby implicating EphB3 as a potential therapeutic target in NSCLC. Cancer Res; 71(3); 1156–66. ©2011 AACR.
The effects of chemical and physical factors on mammalian embryo culture and their importance for the practice of assisted human reproduction
Authors: Petra L. Wale, David K. Gardner
Journal: Human Reproduction Update (2015)

Although laboratory procedures, along with culture media formulations, have improved over the past two decades, the issue remains that human IVF is performed in vitro (literally 'in glass'). Using PubMed, electronic searches were performed using keywords from a list of chemical and physical factors with no limits placed on time. Examples of keywords include oxygen, ammonium, volatile organics, temperature, pH, oil overlays and incubation volume/embryo density. Available clinical and scientific evidence surrounding physical and chemical factors have been assessed and presented here. Development of the embryo outside the body means that it is constantly exposed to stresses that it would not experience in vivo. Sources of stress on the human embryo include identified factors such as pH and temperature shifts, exposure to atmospheric (20%) oxygen and the build-up of toxins in the media due to the static nature of culture. However, there are other sources of stress not typically considered, such as the act of pipetting itself, or the release of organic compounds from the very tissue culture ware upon which the embryo develops. Further, when more than one stress is present in the laboratory, there is evidence that negative synergies can result, culminating in significant trauma to the developing embryo. It is evident that embryos are sensitive to both chemical and physical signals within their microenvironment, and that these factors play a significant role in influencing development and events post transfer. From the viewpoint of assisted human reproduction, a major concern with chemical and physical factors lies in their adverse effects on the viability of embryos, and their long-term effects on the fetus, even as a result of a relatively brief exposure. This review presents data on the adverse effects of chemical and physical factors on mammalian embryos and the importance of identifying, and thereby minimizing, them in the practice of human IVF. Hence, optimizing the in vitro environment involves far more than improving culture media formulations.
Nonspecific recruitment of cytotoxic effector cells in the intestinal mucosa of antigen-primed mice.
Authors: J R Klein, M F Kagnoff
Journal: The Journal of Experimental Medicine (1984)

We have examined cytotoxic responses of lymphocytes derived from the gut epithelium of mice primed systemically and enterically with alloantigens. Both gut intraepithelial (IEL) and splenic lymphocytes from alloantigen-primed mice were found to contain antigen-specific cytotoxic T cell activity. However, after priming, gut IEL also developed high levels of natural killer and spontaneous cytotoxic cell activities. We suggest that this nonspecific activation of additional cytotoxic effector populations during an antigen-specific response is an important host immune defense within the intestinal mucosa.
Reply to F. Bellati et al
Authors: Neil L. Spector, Kimberly L. Blackwell
Journal: Journal of Clinical Oncology (2010)

The antitumor activity of trastuzumab in human epidermal growth factor receptor 2 (HER2) –positive breast cancer has been ascribed to both immunologic and nonimmunologic mechanisms. It is unlikely that any one of these mechanisms alone is responsible for the antitumor activity of trastuzumab. We thank Bellati et al for pointing out the importance of the adaptive immune response as another mechanism involved in mediating trastuzumab antitumor activity. We agree with Bellati et al that HER2-based vaccines represent a promising therapeutic approach in the treatment of breast cancer. Our group is conducting an ongoing study combining lapatinib with a HER2-directed vaccine to further understand the role of the immune system in HER2-directed therapy antitumor activity (ClinicalTrials .gov Identifier: NCT00952692). As we have previously shown in preclinical models, total HER2 blockade using anti-HER2 antibodies generated in response to various HER2 vaccines in combination with lapatinib results in enhanced antitumor activity compared with either treatment alone. These experiments were conducted in cell culture without the addition of immune effector cells, which further implicates the role of nonimmunologic mechanisms in the antitumor activity. The clinical validation of these studies was recently demonstrated in a randomized phase III clinical trial in women with advanced stage HER2-positive breast cancer who had progressed on trastuzumab-containing therapy, where we showed the clinical benefit of combining trastuzumab with lapatinib compared with lapatinib treatment alone. This should dispel some of the concern about possible antagonistic effects of combining trastuzumab with small molecule inhibitors of ErbB2 tyrosine kinase activity. In addition, the article referenced in the correspondence of Bellati et al described the binding of lapatinib to epidermal growth factor receptor by x-ray crystallography, not HER2. To our knowledge, similar x-ray crystallographic studies of lapatinib interaction with HER2 have not been reported. Finally, we completely agree with Bellati et al and Winer and Burstein in their Editorial that greater insight into predictors of response to targeted therapies, such as trastuzumab, is needed. Quantitative HER2 status alone has clearly not been sufficient to predict for clinical response to trastuzumab. To more effectively treat individuals with HER2-positive breast cancer, a greater understanding of the tumor profile and patient immunological status that predict for clinical response to trastuzumab and potentially other HER2-targeted therapies is needed.
Chronic inflammatory demyelinating polyradiculoneuropathy with ataxia
Authors: R C Stockdale, C K Biswas
Journal: Journal of the Royal Society of Medicine (2004)

Nevertheless, in the largest case series SLE developed in only 2 of 108 patients, so the association may be a chance finding. 6REFERENCES 1 Kikuchi M. Lymphadenitis showing focal reticulum cell hyperplasia with nuclear debris and phagocytes: a clinicopathological study [In Japanese].
Efficient Removal of Immunoglobulin Free Light Chains by Hemodialysis for Multiple Myeloma
Authors: Colin A. Hutchison, Paul Cockwell, Steven Reid, Katie Chandler, Graham P. Mead, John Harrison, John Hattersley, Neil D. Evans, Mike J. Chappell, Mark Cook, Hermann Goehl, Markus Storr, Arthur R. Bradwell
Journal: Journal of the American Society of Nephrology (2007)

Of patients with newly diagnosed multiple myeloma, approximately 10% have dialysis-dependent acute renal failure, with cast nephropathy, caused by monoclonal free light chains (FLC). Of these, 80 to 90% require long-term renal replacement therapy. Early treatment by plasma exchange reduces serum FLC concentrations, but randomized, controlled trials have shown no evidence of renal recovery. This outcome can be explained by the low efficiency of the procedure. A model of FLC production, distribution, and metabolism in patients with myeloma indicated that plasma exchange might remove only 25% of the total amount during a 3-wk period. For increasing FLC removal, extended hemodialysis with a protein-leaking dialyzer was used. <i>In vitro</i> studies indicated that the Gambro HCO 1100 dialyzer was the most efficient of seven tested. Model calculations suggested that it might remove 90% of FLC during 3 wk. This dialyzer then was evaluated in eight patients with myeloma and renal failure. Serum FLC reduced by 35 to 70% within 2 hr, but reduction rates slowed as extravascular re-equilibration occurred. FLC concentrations rebounded on successive days unless chemotherapy was effective. Five additional patients with acute renal failure that was caused by cast nephropathy then were treated aggressively, and three became dialysis independent. A total of 1.7 kg of FLC was removed from one patient during 6 wk. Extended hemodialysis with the Gambro HCO 1100 dialyzer allowed continuous, safe removal of FLC in large amounts. Proof of clinical value now will require larger studies.
European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. III. Assessment of the construct validity of the preliminary activity criteria
Authors: G Valentini
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To further assess the construct validity of the three European Scleroderma Study Group (EScSG) preliminary activity indices for systemic sclerosis (SSc): for SSc as a whole, for diffuse SSc (dcSSc), and for limited SSc (lcSSc). <b>Methods:</b> 30/290 SSc clinical charts collected for the EScSG study used to develop activity criteria for SSc were selected and sent to four clinical experts in SSc. The experts ranked the charts from 1 to 30 (1=lowest activity, 30=highest activity). The relationships among the ranks given by each investigator and each of the three scores, and between any two of the ranks were investigated. <b>Results:</b> A consistently significant correlation (<i>r</i><sub>s</sub>=0.530–0.712) was found between the ranks given by each of the four investigators and the index for the entire patient group. A similar level of agreement was detected between each couple of the four experts (<i>r</i><sub>s</sub>=0.428–0.720). Moreover, the ranks given in patients with an index &gt;3 were significantly higher than those given for patients with an index ⩽3. This cut off point had previously been shown to best discriminate patients with active disease. <b>Conclusions:</b> Of the originally developed activity indexes, the whole series index has been externally validated. The index comprises the first preliminary, but necessary, groundwork to improve the concept of disease activity in SSc, which is still ill defined. It can be used as a preliminary activity index in clinical investigational studies.
Relationship between supramaximal flows and flow-limiting mechanisms
Authors: H Sala, F Galindez, A Badolati, D Rodenstein
Journal: European Respiratory Journal (1996)

The aim of this study was to evaluate the relationship between supramaximal flows (SF) and indices of airway mechanics. We studied 26 asymptomatic young subjects (13 smokers, mean +/- SD 15.9 +/- 6.6 pack-years. Subjects performed maximal expiratory flow-volume (MEFV) curves, according to the American Thoracic Society (ATS) criteria, on a rolling-seal spirometer and then repeated them through a specially devised valve, which occluded the mouthpiece either 3 or 6 times.s-1 with a ratio of open:closed time of 3:1. Envelope MEFV curves for 3 and 6 Hz occlusions were constructed passing through the SF obtained after each occlusion, and the increment in flow at 50% of vital capacity was measured with respect to the basal curve (delta V' max50). We found that the delta V' max50 at 3 and 6 Hz correlated to the baseline forced mid-expiratory flow (FEF25-75) in % of predicted value (r = -0.73 and r = -0.55, respectively). our results suggest that inhomogeneities within the lung are an important mechanism in the occurrence of supramaximal flow in normal subjects.
Phase II Placebo-Controlled Randomized Discontinuation Trial of Sorafenib in Patients With Metastatic Renal Cell Carcinoma
Authors: Mark J. Ratain, Tim Eisen, Walter M. Stadler, Keith T. Flaherty, Stan B. Kaye, Gary L. Rosner, Martin Gore, Apurva A. Desai, Amita Patnaik, Henry Q. Xiong, Eric Rowinsky, James L. Abbruzzese, Chenghua Xia, Ronit Simantov, Brian Schwartz, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2006)

This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma.Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with > or = 25% tumor shrinkage continued open-label sorafenib; patients with > or = 25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib.Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of > or = 25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were progression free versus 18% of the placebo-treated patients (P = .0077). Median progression-free survival (PFS) from randomization was significantly longer with sorafenib (24 weeks) than placebo (6 weeks; P = .0087). Median overall PFS was 29 weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was readministered in 28 patients whose disease progressed on placebo; these patients continued on sorafenib until further progression, for a median of 24 weeks. Common adverse events were skin rash/desquamation, hand-foot skin reaction, and fatigue; 9% of patients discontinued therapy, and no patients died from toxicity.Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.
Prevention Strategies for Cardiovascular Disease in HIV-Infected Patients
Authors: James H. Stein, Colleen M. Hadigan, Todd T. Brown, Ellen Chadwick, Judith Feinberg, Nina Friis-Møller, Anuradha Ganesan, Marshall J. Glesby, David Hardy, Robert C. Kaplan, Peter Kim, Janet Lo, Esteban Martinez, James M. Sosman
Journal: Circulation (2008)