tbuckley/cabot-search huggingface dataset:
A Balance between Positive and Negative Signals in Cytotoxic Lymphocytes Regulates the Polarization of Lipid Rafts during the Development of Cell-Mediated Killing
Authors: Zhenkun Lou, Dragan Jevremovic, Daniel D. Billadeau, Paul J. Leibson
Journal: The Journal of Experimental Medicine (2000)

Plasma membrane microdomains containing sphingolipids and cholesterol (lipid rafts) are enriched in signaling molecules. The cross-linking of certain types of cell surface receptors initiates the redistribution of these lipid rafts, resulting in the formation of signaling complexes. However, little is known about the regulation of the initial raft redistribution and whether negative regulatory signaling pathways target this phase of cellular activation. We used natural killer (NK) cells as a model to investigate the regulation of raft redistribution, as both positive and negative signals have been implicated in the development of their cellular function. Here we show that after NK cells form conjugates with sensitive tumor cells, rafts become polarized to the site of target recognition. This redistribution of lipid rafts requires the activation of both Src and Syk family protein tyrosine kinases. In contrast, engagement of major histocompatibility complex (MHC)-recognizing killer cell inhibitory receptors (KIRs) on NK cells by resistant, MHC-bearing tumor targets blocks raft redistribution. This inhibition is dependent on the catalytic activity of KIR-associated SHP-1, a Src homology 2 (SH2) domain containing tyrosine phosphatase. These results suggest that the influence of integrated positive and negative signals on raft redistribution critically influences the development of cell-mediated cytotoxicity.
TRPM7 Is Required for Breast Tumor Cell Metastasis
Authors: Jeroen Middelbeek, Arthur J. Kuipers, Linda Henneman, Daan Visser, Ilse Eidhof, Remco van Horssen, Bé Wieringa, Sander V. Canisius, Wilbert Zwart, Lodewyk F. Wessels, Fred C.G.J. Sweep, Peter Bult, Paul N. Span, Frank N. van Leeuwen, Kees Jalink
Journal: Cancer Research (2012)

TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II-based cellular tension, thereby modifying focal adhesion number, cell-cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation.
Relationship between cardiac metaiodobenzylguanidine uptake and hemodynamic, functional and neurohormonal parameters in patients with heart failure
Authors: Paul A.R. de Milliano, Berthe L.F. van Eck‐Smit, Pieter A. van Zwieten, Andre C. de Groot, Jan G.P. Tijssen, Kong I. Lie
Journal: European Journal of Heart Failure (2001)
Low dose spiral CT combined with selective use of PET scans can detect early lung cancer
Authors: K Ryanna
Journal: Thorax (2003)

▴ Pastorino U, Bellomi M, Landoni C, et al . Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2 year results. Lancet2003;362:593–7 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This non-randomised study of 1035 smokers (⩾20 pack years) evaluated screening using positron emission tomography (PET) in addition to spiral computed tomography (CT) to improve assessment of lesions. All patients had baseline CT and annual scans for 5 years. Calcified nodular lesions or non-calcified nodules (NCN) <5 mm were deemed … [1]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DPastorino%26rft.auinit1%253DU.%26rft.volume%253D362%26rft.issue%253D9384%26rft.spage%253D593%26rft.epage%253D597%26rft.atitle%253DEarly%2Blung-cancer%2Bdetection%2Bwith%2Bspiral%2BCT%2Band%2Bpositron%2Bemission%2Btomography%2Bin%2Bheavy%2Bsmokers%253A%2B2-year%2Bresults.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252803%252914188-8%26rft_id%253Dinfo%253Apmid%252F12944057%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0140-6736(03)14188-8&link_type=DOI [3]: /lookup/external-ref?access_num=12944057&link_type=MED&atom=%2Fthoraxjnl%2F58%2F12%2F1082.atom [4]: /lookup/external-ref?access_num=000184904100006&link_type=ISI
Reconstitution dynamics of plasmacytoid and myeloid dendritic cell precursors after allogeneic myeloablative hematopoietic stem cell transplantation
Authors: Francesco F. Fagnoni, Barbara Oliviero, Giovanna Giorgiani, Piero De Stefano, Anna Dehò, Carlo Zibera, Nadia Gibelli, Rita Maccario, GianAntonio Da Prada, Marco Zecca, Franco Locatelli
Journal: Blood (2004)
Impairment of Social Perception Associated With Lesions of the Prefrontal Cortex
Authors: Linda Mah, Miriam C. Arnold, Jordan Grafman
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Behavioral and social impairments have been frequently reported after damage to the prefrontal cortex in humans. This study evaluated social perception in patients with prefrontal cortex lesions and compared their performance on a social perception task with that of healthy volunteers. METHOD: Thirty-three patients with prefrontal cortex lesions and 31 healthy volunteers were tested with the Interpersonal Perception Task. In this task, subjects viewed videotaped social interactions and relied primarily on nonverbal cues to make interpersonal judgments, such as determining the degree of intimacy between two persons depicted in the videotaped scene. Patients with prefrontal cortex lesions were classified according to lesion involvement of specific regions, including the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. RESULTS: Relative to the comparison subjects, patients whose lesions involved the orbitofrontal cortex demonstrated impaired social perception. Contrary to predictions, patients with lesions in the dorsolateral prefrontal cortex also showed deficits in using social cues to make interpersonal judgments. All patients, particularly those with lesions in the dorsolateral prefrontal cortex, showed poorer insight into their deficits, relative to healthy volunteers. CONCLUSIONS: These findings of deficits in social perception after damage to the orbitofrontal cortex extend previous clinical and experimental evidence of damage-related impairment in other aspects of social cognition, such as the ability to accurately evaluate emotional facial expressions. In addition, the results suggest that the dorsolateral prefrontal cortex is recruited when inferences about social interactions are made on the basis of nonverbal information.
Blood Pressure, Lipids, and Obesity Are Associated With Retinopathy
Authors: Hendrik A. van Leiden, Jacqueline M. Dekker, Annette C. Moll, Giel Nijpels, Robert J. Heine, Lex M. Bouter, Coen D.A. Stehouwer, Bettine C.P. Polak
Journal: Diabetes Care (2002)

OBJECTIVE—To study potential risk factors for retinopathy in diabetic and nondiabetic individuals. RESEARCH DESIGN AND METHODS—The Hoorn Study is a population-based study including 2,484 50- to 74-year-old Caucasians. A subsample of 626 individuals stratified by age, sex, and glucose tolerance underwent extensive measurements during 1989–1992, including ophthalmologic examination and two-field 45-degree fundus photography. The prevalence of (diabetic) retinopathy was assessed among individuals with normal glucose metabolism (NGM) and impaired glucose metabolism (IGM) and individuals with newly diagnosed diabetes mellitus (NDM) and known diabetes mellitus (KDM) (new World Health Organization 1999 criteria). RESULTS—The prevalence of retinopathy was 9% in NGM, 11% in IGM, 13% in NDM, and 34% in KDM. Retinopathy worse than minimal nonproliferative diabetic retinopathy was present in 8% in KDM and 0–2% in other glucose categories. The prevalence of retinopathy was positively associated with elevated blood pressure, BMI, cholesterol, and triglyceride serum levels in all glucose categories. The age-, sex-, and glucose metabolism category–adjusted odds ratios were 1.5 (95% CI 1.2–1.9), 1.3 (1.0–1.7), and 1.3 (1.0–1.6) per SD increase of systolic blood pressure, BMI, and total cholesterol concentration, respectively, and 1.2 (1.0–1.5) per 50% increase of triglyceride level. Elevated blood pressure and plasma total and LDL cholesterol levels showed associations with retinal hard exudates. CONCLUSIONS—Retinopathy is a multifactorial microvascular complication, which, apart from hyperglycemia, is associated with blood pressure, lipid concentrations, and BMI.
Meta-analysis of Risk Reduction Estimates Associated With Risk-Reducing Salpingo-oophorectomy in BRCA1 or BRCA2 Mutation Carriers
Authors: T. R. Rebbeck, N. D. Kauff, S. M. Domchek
Journal: JNCI Journal of the National Cancer Institute (2009)

Risk-reducing salpingo-oophorectomy (RRSO) is widely used by carriers of BRCA1 or BRCA2 (BRCA1/2) mutations to reduce their risks of breast and ovarian cancer. To guide women and their clinicians in optimizing cancer prevention strategies, we summarized the magnitude of the risk reductions in women with BRCA1/2 mutations who have undergone RRSO compared with those who have not.All reports of RRSO and breast and/or ovarian or fallopian tube cancer in BRCA1/2 mutation carriers published between 1999 and 2007 were obtained from a PubMed search. Hazard ratio (HR) estimates were identified directly from the original articles. Pooled results were computed from nonoverlapping studies by fixed-effects meta-analysis.Ten studies investigated breast or gynecologic cancer outcomes in BRCA1/2 mutation carriers who had undergone RRSO. Breast cancer outcomes were investigated in three nonoverlapping studies of BRCA1/2 mutation carriers, four of BRCA1 mutation carriers, and three of BRCA2 mutation carriers. Gynecologic cancer outcomes were investigated in three nonoverlapping studies of BRCA1/2 mutation carriers and one of BRCA1 mutation carriers. RRSO was associated with a statistically significant reduction in risk of breast cancer in BRCA1/2 mutation carriers (HR = 0.49; 95% confidence interval [CI] = 0.37 to 0.65). Similar risk reductions were observed in BRCA1 mutation carriers (HR = 0.47; 95% CI = 0.35 to 0.64) and in BRCA2 mutation carriers (HR = 0.47; 95% CI = 0.26 to 0.84). RRSO was also associated with a statistically significant reduction in the risk of BRCA1/2-associated ovarian or fallopian tube cancer (HR = 0.21; 95% CI = 0.12 to 0.39). Data were insufficient to obtain separate estimates for ovarian or fallopian tube cancer risk reduction with RRSO in BRCA1 or BRCA2 mutation carriers.The summary estimates presented here indicate that RRSO is strongly associated with reductions in the risk of breast, ovarian, and fallopian tube cancers and should provide guidance to women in planning cancer risk reduction strategies.
Endothelial cells express a spectrin-like cytoskeletal protein.
Authors: C Heltianu, I Bogdan, E Constantinescu, M Simionescu
Journal: Circulation Research (1986)

Vascular endothelium was investigated by indirect immunofluorescence and immunoautoradiography for the possible presence of spectrin-like molecules. Antibodies were raised against electrophoretically purified rat, rabbit, and bovine red blood cell spectrin and against rabbit brain fodrin. Antibody specificity was assessed by immunoblotting and double-diffusion technique. Homogenates of endothelial cells freshly isolated from heart microvasculature or aorta, as well as cultured aortic endothelial cells, were analyzed by gel electrophoresis. Immunoautoradiograms of gels incubated with spectrin specific antibody, followed by radio-labeled protein A, revealed two bands of electrophoretic mobility similar to that of the alpha- and beta-subunits of spectrin. Indirect immunofluorescence of endothelial cells, both in situ and in vitro, showed the existence of a protein which cross-reacted with the antibodies against spectrin and fodrin. Controls, in which endothelial cells were exposed to spectrin antibody absorbed with pure spectrin or preimmune serum, were negative. These findings indicate that endothelial cells express a protein antigenically related to the spectrin family; both spectrin- and fodrin-like molecules, in various proportions, may coexist. In the endothelial cell, these proteins may play an important role in modulation of the cytoskeleton in response to various stimuli, and in maintaining the biochemically differentiated microdomains of plasmalemma.
Molecular mechanisms of intensive care unit-acquired weakness
Authors: S. Bloch, M.I. Polkey, M. Griffiths, P. Kemp
Journal: European Respiratory Journal (2011)

Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and important clinical consequence of critical illness. It is associated with significant morbidity and mortality. The aetiology of this disease is not well understood. The purpose of this article is to review our understanding of the molecular pathogenesis of ICUAW in the context of current knowledge of clinical risk factors and aetiology. Key features of the disease are loss of muscle mass resulting from a shift in the dynamic balance of muscle protein synthesis and breakdown and a reduction in force-generating capacity. These alternations are secondary to neuropathy, disruption of the myofilament structure and function, a disrupted sarcoplasmic reticulum, electrical inexcitability and bioenergenetic failure. As knowledge and understanding of ICUAW grows, potential therapeutic targets will be identified, hopefully leading to multiple strategies for prevention and treatment of this important condition.
KIR: Diverse, Rapidly Evolving Receptors of Innate and Adaptive Immunity
Authors: Carlos Vilches, Peter Parham
Journal: Annual Review of Immunology (2002)

KIR genes have evolved in primates to generate a diverse family of receptors with unique structures that enable them to recognize MHC-class I molecules with locus and allele-specificity. Their combinatorial expression creates a repertoire of NK cells that surveys the expression of almost every MHC molecule independently, thus antagonizing the spread of pathogens and tumors that subvert innate and adaptive defense by selectively downregulating certain MHC class I molecules. The genes encoding KIR that recognize classical MHC molecules have diversified rapidly in human and primates; this contrasts with conservation of immunoglobulin- and lectin-like receptors for nonclassical MHC molecules. As a result of the variable KIR-gene content in the genome and the polymorphism of the HLA system, dissimilar numbers and qualities of KIR:HLA pairs function in different humans. This diversity likely contributes variability to the function of NK cells and T-lymphocytes by modulating innate and adaptive immune responses to specific challenges.
The Combi-Targeting Concept: <i>In vitro</i> and <i>In vivo</i> Fragmentation of a Stable Combi-Nitrosourea Engineered to Interact with the Epidermal Growth Factor Receptor while Remaining DNA Reactive
Authors: Qiyu Qiu, Juozas Domarkas, Ranjita Banerjee, Nuria Merayo, Fouad Brahimi, James P. McNamee, Bernard F. Gibbs, Bertrand J. Jean-Claude
Journal: Clinical Cancer Research (2007)

Abstract Purpose: JDA58 (NSC 741282), a “combi-molecule” optimized in the context of the “combi-targeting concept,” is a nitrosourea moiety tethered to an anilinoquinazoline. Here, we sought to show its binary epidermal growth factor receptor (EGFR)/DNA targeting property and to study its fragmentation in vitro and in vivo. Experimental Design: The fragmentation of JDA58 was detected in cells in vitro and in vivo by fluorescence microscopy and tandem mass spectrometry. EGFR phosphorylation and DNA damage were determined by Western blotting and comet assay, respectively. Tumor data were examined for statistical significance using the Student's t test. Results: JDA58 inhibited EGFR tyrosine kinase (IC50, 0.2 μmol/L) and blocked EGFR phosphorylation in human DU145 prostate cancer cells. It induced significant levels of DNA damage in DU145 cells in vitro or in vivo and showed potent antiproliferative activity both in vitro and in a DU145 xenograft model. In cell-free medium, JDA58 was hydrolyzed to JDA35, a fluorescent amine that could be observed in tumor cells both in vitro and in vivo. In tumor cells in vitro or in vivo, or in plasma collected from mice, the denitrosated species JDA41 was the predominant metabolite. However, mass spectrometric analysis revealed detectable levels of the hydrolytic product JDA35 in tumor cells both in vitro and in vivo. Conclusions: The results in toto suggest that growth inhibition in vitro and in vivo may be sustained by the intact combi-molecule plus JDA35 plus JDA41, three inhibitors of EGFR, and the concomitantly released DNA-damaging species. This leads to a model wherein a single molecule carries a complex multitargeted-multidrug combination.
Studies of the Transferrin Receptor on both Human Reticulocytes and Nucleated Human Cells in Culture
Authors: Janet L. Frazier, Jennifer H. Caskey, Mark Yoffe, Paul A. Seligman
Journal: Journal of Clinical Investigation (1982)

The transferrin receptor, present on reticulocytes and nucleated cells in tissue culture, has been measured with both immunoassay techniques and transferrin binding studies. The total cellular immunoreactive receptor is rapidly lost from erythrocytes during the process of reticulocyte maturation (from as many as 400,000 molecules to <20,000 molecules/reticulocyte). This event parallels the loss of cell surface transferrin binding sites and RNA content, and correlates with previous studies that have measured the decline in hemoglobin synthesis.
VITAMIN E, OXIDATIVE STRESS, AND INFLAMMATION
Authors: U. Singh, S. Devaraj, I. Jialal
Journal: Annual Review of Nutrition (2005)

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Western world. Its incidence has also been increasing lately in developing countries. Several lines of evidence support a role for oxidative stress and inflammation in atherogenesis. Oxidation of lipoproteins is a hallmark in atherosclerosis. Oxidized low-density lipoprotein induces inflammation as it induces adhesion and influx of monocytes and influences cytokine release by monocytes. A number of proinflammatory cytokines such as interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) modulate monocyte adhesion to endothelium. C-reactive protein (CRP), a prototypic marker of inflammation, is a risk marker for CVD and it could contribute to atherosclerosis. Hence, dietary micronutrients having anti-inflammatory and antioxidant properties may have a potential beneficial effect with regard to cardiovascular disease. Vitamin E is a potent antioxidant with anti-inflammatory properties. Several lines of evidence suggest that among different forms of vitamin E, alpha-tocopherol (AT) has potential beneficial effects with regard to cardiovascular disease. AT supplementation in human subjects and animal models has been shown to decrease lipid peroxidation, superoxide (O2-) production by impairing the assembly of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase as well as by decreasing the expression of scavenger receptors (SR-A and CD36), particularly important in the formation of foam cells. AT therapy, especially at high doses, has been shown to decrease the release of proinflammatory cytokines, the chemokine IL-8 and plasminogen activator inhibitor-1 (PAI-1) levels as well as decrease adhesion of monocytes to endothelium. In addition, AT has been shown to decrease CRP levels, in patients with CVD and in those with risk factors for CVD. The mechanisms that account for nonantioxidant effects of AT include the inhibition of protein kinase C, 5-lipoxygenase, tyrosine-kinase as well as cyclooxygenase-2. Based on its antioxidant and anti-inflammatory activities, AT (at the appropriate dose and form) could have beneficial effects on cardiovascular disease in a high-risk population.
Comparison of Three Fluid Solutions for Resuscitation in Dengue Shock Syndrome
Authors: Bridget A. Wills, Nguyen M. Dung, Ha T. Loan, Dong T.H. Tam, Tran T.N. Thuy, Le T.T. Minh, Tran V. Diet, Nguyen T. Hao, Nguyen V. Chau, Kasia Stepniewska, Nicholas J. White, Jeremy J. Farrar
Journal: New England Journal of Medicine (2005)

Dengue shock syndrome is characterized by severe vascular leakage and disordered hemostasis and progresses to death in 1 to 5 percent of cases. Although volume replacement is recognized as the critical therapeutic intervention, World Health Organization management guidelines remain empirical rather than evidence-based.
It Is Follicular… . So, Why CHOP?
Authors: Chadi Nabhan
Journal: Journal of Clinical Oncology (2007)

instability, at least in Eurasian patients, without referring to matching, normal DNA.Our article 1 was an extensive analysis of the frequency of allelic variants for these five markers in a series of 1,206 individuals belonging to 55 distinct populations worldwide.We did not analyze these markers in all populations of all countries.Instead, germline DNA samples from 52 of 55 analyzed populations were obtained from the Human Genome Diversity Project-Centre d'Etude du Polymorphisme Humain diversity panel, which is the best approximation available of the world populations. 3As Cossio et al pointed out, the Brazilian population is heterogeneous with, apart from Native Americans, a very large proportion of individuals of European and African origin.In our multipopulation study, we analyzed two American Indian populations from South America, but we did not indicate that they were representative of the actual Brazilian population.We also analyzed seven population groups from sub-Saharan Africa and eight population groups from Europe.The allelic characteristics of these mononucleotide repeat loci in the actual Brazilian population can be deduced from those of the different American Indian, European, and African populations from which they originate, according to the relative frequencies of these origins.Accordingly, because Cossio et al report that 146 million of 188 million inhabitants of Brazil claim at least 10% sub-Saharan African ancestry, it is not surprising that the actual Brazilian population presents a relatively high percentage of size variants for the BAT-25 and BAT-26 markers.We showed that BAT-25 and BAT-26 variant allele frequencies can be as high as 57% and 15% in the San and Biaka pygmy populations, respectively, and within a 4.0% to 12.5% range in less isolated African populations like the Yoruba from Nigeria or Mandenka from Senegal.As we were aware of worldwide allelic variation at these marker loci, we proposed that five mononucleotide repeats, instead of one or two, should be analyzed.We showed that 99.8% of the worldwide population that we examined did not present more than two markers of the pentaplex with variant alleles. 1 The three exceptions (with three variant alleles) belong to specific populations of the Biaka pygmy and San people.Since we confirmed that MSI-H tumors showed instability in at least four markers, and more frequently in five of the markers, we concluded that these five markers could be used, without referring to matching normal DNA, to determine the MSI status of tumors from all human populations.We can affirm that this fact is also true for Brazilian patients, whatever their ethnic background, provided that the five markers of the pentaplex are analyzed.