tbuckley/cabot-search huggingface dataset:
Induction of stress proteins in cultured myogenic cells. Molecular signals for the activation of heat shock transcription factor during ischemia.
Authors: I J Benjamin, S Horie, M L Greenberg, R J Alpern, R S Williams
Journal: Journal of Clinical Investigation (1992)

Expression of major stress proteins is induced rapidly in ischemic tissues, a response that may protect cells from ischemic injury. We have shown previously that transcriptional induction of heat-shock protein 70 by hypoxia results from activation of DNA binding of a preexisting, but inactive, pool of heat shock factor (HSF). To determine the intracellular signals generated in hypoxic or ischemic cells that trigger HSF activation, we examined the effects of glucose deprivation and the metabolic inhibitor rotenone on DNA-binding activity of HSF in cultured C2 myogenic cells grown under normoxic conditions. Whole-cell extracts were examined in gel mobility shift assays using a 39-bp synthetic oligonucleotide containing a consensus heat-shock element as probe. ATP pools were determined by high-pressure liquid chromatography and intracellular pH (pHi) was measured using a fluorescent indicator. Glucose deprivation alone reduced the cellular ATP pool to 50% of control levels but failed to activate HSF. However, 2 x 10(-4) M rotenone induced DNA binding of HSF within 30 min, in association with a fall in ATP to 30% of control levels, and a fall in pHi from 7.3 to 6.9. Maneuvers (sodium propionate and amiloride) that lowered pHi to 6.7 without ATP depletion failed to activate HSF. Conversely, in studies that lowered ATP stores at normal pH (high K+/nigericin) we found induction of HSF-DNA binding activity. Our data indicate that the effects of ATP depletion alone are sufficient to induce the DNA binding of HSF when oxidative metabolism is impaired, and are consistent with a model proposed recently for transcriptional regulation of stress protein genes during ischemia.
Osteopontin Promotes Integrin Activation through Outside-In and Inside-Out Mechanisms: OPN-CD44V Interaction Enhances Survival in Gastrointestinal Cancer Cells
Authors: Jia-Lin Lee, Mei-Jung Wang, Putty-Reddy Sudhir, Gen-Der Chen, Chin-Wen Chi, Jeou-Yuan Chen
Journal: Cancer Research (2007)

Abstract Osteopontin (OPN) and splice variants of CD44 (CD44V) have independently been identified as markers for tumor progression. In this study, we show that both OPN and CD44V are frequently overexpressed in human gastric cancer and that OPN-engaged CD44V ligation confers cells an increased survival mediated through integrin activation. First, we show that OPN treatment confers cells an increased resistance to UV-induced apoptosis. The OPN-mediated antiapoptosis is dependent on the expression of the variant exon 6 (V6)- or V7-containing CD44 as shown by overexpression of individual CD44V in gastric AZ521 cells that express no or very low level of endogenous CD44 and by knockdown of the constitutively expressed V6-containing CD44 isoforms in colon HT29 cells. Although OPN also interacts with RGD integrins, OPN-RGD sequence is dispensable for OPN-mediated antiapoptosis. OPN-induced antiapoptosis is mainly attributed to the engagement of CD44V isoforms and the relay of an inside-out signaling via Src activity, leading to robust integrin activation. Furthermore, OPN-elicited antiapoptosis was observed when cells were plated on fibronectin but not on poly-d-lysin, and preincubation of cells with anti-integrin β1 antibody to block integrin-extracellular matrix (ECM) interaction or ectopic expression of the dominant-negative forms of focal adhesion kinase to block ECM-derived signal abolished OPN-induced survival, suggesting that OPN-elicited antiapoptotic function is propagated from matrix transduced by integrin. Taken together, we showed that OPN-CD44V interaction promotes ECM-derived survival signal mediated through integrin activation, which may play an important role in the pathogenic development and progression of gastric cancer. [Cancer Res 2007;67(5):2089–97]
Thrombin Receptor Protease-Activated Receptor 4 Is a Key Regulator of Exaggerated Intimal Thickening in Diabetes Mellitus
Authors: Goran Pavic, Maria Grandoch, Seema Dangwal, Klaus Jobi, Bernhard H. Rauch, Anke Doller, Alexander Oberhuber, Payam Akhyari, Karsten Schrör, Jens W. Fischer, Anke C. Fender
Journal: Circulation (2014)

Diabetes mellitus predisposes to thrombotic and proliferative vascular remodeling, to which thrombin contributes via activation of protease-activated receptor (PAR) 1. However, the use of PAR-1 inhibitors to suppress remodeling may be limited by severe bleeding. We recently reported upregulation of an additional thrombin receptor, PAR-4, in human vascular smooth muscle cells exposed to high glucose and have now examined PAR-4 as a novel mediator linking hyperglycemia, hypercoagulation, and vascular remodeling in diabetes mellitus.PAR-4 expression was increased in carotid atherectomies and saphenous vein specimens from diabetic versus nondiabetic patients and in aorta and carotid arteries from streptozotocin-diabetic versus nondiabetic C57BL/6 mice. Vascular PAR-1 mRNA was not increased in diabetic mice. Ligated carotid arteries from diabetic mice developed more extensive neointimal hyperplasia and showed greater proliferation than arteries from nondiabetic mice. The augmented remodeling response was absent in diabetic mice deficient in PAR-4. At the cellular level, PAR-4 expression was controlled via the mRNA stabilizing actions of human antigen R, which accounted for the stimulatory actions of high glucose, angiotensin II, and H2O2 on PAR-4 expression, whereas cicaprost via protein kinase A activation counteracted this effect.PAR-4 appears to play a hitherto unsuspected role in diabetic vasculopathy. The development of PAR-4 inhibitors might serve to limit mainly proliferative processes in restenosis-prone diabetic patients, particularly those patients in whom severe bleeding attributed to selective PAR-1 blockade or complete thrombin inhibition must be avoided or those who do not require anticoagulation.
Tightly spiral shaped bacteria in the human stomach: another cause of active chronic gastritis?
Authors: A Morris, M R Ali, L Thomsen, B Hollis
Journal: Gut (1990)

Tightly spiral shaped Gram negative bacteria were seen in the gastric biopsies obtained from two patients undergoing gastroscopy. Active chronic gastritis was present in both patients and one patient also had gastric ulceration. Attempts to culture the organism by a number of methods were unsuccessful but positive urease results were obtained in both patients. Both patients were treated with colloidal bismuth subcitrate. Biopsies taken after treatment showed resolution of infection and histological gastritis. These results suggest that Helicobacter pylori is not the only organism associated with chronic active gastritis in man.
Evolutionary Analysis of the Contact System Indicates that Kininogen Evolved Adaptively in Mammals and in Human Populations
Authors: Rachele Cagliani, Diego Forni, Stefania Riva, Uberto Pozzoli, Marta Colleoni, Nereo Bresolin, Mario Clerici, Manuela Sironi
Journal: Molecular Biology and Evolution (2013)

Activation of the contact system leads to the cleavage of kininogen by plasma kallikrein resulting in kinin release and in the initiation of the intrinsic pathway of coagulation. Proteolysis of kininogen also generates antimicrobial peptides (AMPs) and can be induced by diverse pathogens. Thus, the contact system is regarded as a branch of innate immunity. We performed an evolutionary analysis of contact system genes by analyzing both inter- and intraspecies diversity. Results indicated that mammalian kininogen genes evolved adaptively. Positively selected sites are located in all protein domains with the exclusion of the bradykinin region and also involve AMP sequences (including the highly effective NAT26 peptide); positively selected sites also occur at alternative cleavage sites for neutrophil-released kinins. Population genetic analysis in humans indicated that a region of the kininogen gene (KNG1) has been a target of long-standing multiallelic balancing selection and that the coalescence time of the haplotype phylogeny dates back to the split between the humans and chimpanzees. No selection signature was detected in the Pan troglodytes KNG1 gene or in human genes encoding other components of the contact system. The selection targets in human KNG1 might be accounted for by variants with transcriptional regulatory activity. Results herein indicate a continuum in selective pressure acting on different timescales and targeting KNG1. This is in line with evidences suggesting a central role for kininogen in modulating of immune response and with its being a target of an extremely diverse array of pathogen species.
patient's view
Authors: Maria Tomasa, Giorgina Barbara Piccoli
Journal: BMJ (2004)

My nickname is Tommy. At the time of the story I was 35 years old.1 I have been diabetic almost all my life, and this has had a big effect on me. I have wanted a baby since the day of my marriage, or even before that. Someone asked me if I wanted a baby to feel more “normal.” That is not the reason. I wanted a baby because it is a fundamental part of life and because I needed a child. I wanted it. When you deeply want something you have no particular reasons for doing it; you just want it day and night. …
Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis
Authors: Ludovic Arnold, Adeline Henry, Françoise Poron, Yasmine Baba-Amer, Nico van Rooijen, Anne Plonquet, Romain K. Gherardi, Bénédicte Chazaud
Journal: The Journal of Experimental Medicine (2007)

Macrophages (MPs) are important for skeletal muscle regeneration in vivo and may exert beneficial effects on myogenic cell growth through mitogenic and antiapoptotic activities in vitro. However, MPs are highly versatile and may exert various, and even opposite, functions depending on their activation state. We studied monocyte (MO)/MP phenotypes and functions during skeletal muscle repair. Selective labeling of circulating MOs by latex beads in CX3CR1GFP/+ mice showed that injured muscle recruited only CX3CR1lo/Ly-6C+ MOs from blood that exhibited a nondividing, F4/80lo, proinflammatory profile. Then, within muscle, these cells switched their phenotype to become proliferating antiinflammatory CX3CR1hi/Ly-6C− cells that further differentiated into F4/80hi MPs. In vitro, phagocytosis of muscle cell debris induced a switch of proinflammatory MPs toward an antiinflammatory phenotype releasing transforming growth factor β1. In co-cultures, inflammatory MPs stimulated myogenic cell proliferation, whereas antiinflammatory MPs exhibited differentiating activity, assessed by both myogenin expression and fusion into myotubes. Finally, depletion of circulating MOs in CD11b–diphtheria toxin receptor mice at the time of injury totally prevented muscle regeneration, whereas depletion of intramuscular F4/80hi MPs at later stages reduced the diameter of regenerating fibers. In conclusion, injured skeletal muscle recruits MOs exhibiting inflammatory profiles that operate phagocytosis and rapidly convert to antiinflammatory MPs that stimulate myogenesis and fiber growth.
Chlorophyll c–Containing Plastid Relationships Based on Analyses of a Multigene Data Set with All Four Chromalveolate Lineages
Authors: Tsvetan R. Bachvaroff, M. Virginia Sanchez Puerta, Charles F. Delwiche
Journal: Molecular Biology and Evolution (2005)

The chlorophyll c–containing algae comprise four major lineages: dinoflagellates, haptophytes, heterokonts, and cryptophytes. These four lineages have sometimes been grouped together based on their pigmentation, but cytological and rRNA data had suggested that they were not a monophyletic lineage. Some molecular data support monophyly of the plastids, while other plastid and host data suggest different relationships. It is uncontroversial that these groups have all acquired plastids from another eukaryote, probably from the red algal lineage, in a secondary endosymbiotic event, but the number and sequence of such event(s) remain controversial. Understanding chlorophyll c–containing plastid relationships is a first step towards determining the number of endosymbiotic events within the chromalveolates. We report here phylogenetic analyses using 10 plastid genes with representatives of all four chromalveolate lineages. This is the first organellar genome-scale analysis to include both haptophytes and dinoflagellates. Concatenated analyses support the monophyly of the chlorophyll c–containing plastids and suggest that cryptophyte plastids are the basal member of the chlorophyll c–containing plastid lineage. The gene psbA, which has at times been used for phylogenetic purposes, was found to differ from the other genes in its placement of the dinoflagellates and the haptophytes, and in its lack of support for monophyly of the green and red plastid lineages. Overall, the concatenated data are consistent with a single origin of chlorophyll c–containing plastids from red algae. However, these data cannot test several key hypothesis concerning chromalveolate host monophyly, and do not preclude the possibility of serial transfer of chlorophyll c–containing plastids among distantly related hosts.
Celiac disease and non-celiac gluten sensitivity
Authors: Benjamin Lebwohl, Jonas F Ludvigsson, Peter H R Green
Journal: BMJ (2015)

Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.
Catastrophic secondary antiphospholipid syndrome with concomitant antithrombin III deficiency.
Authors: V R Peddi, K S Kant
Journal: Journal of the American Society of Nephrology (1995)

The association between thrombotic events and primary or secondary antiphospholipid/anticardiolipin syndrome is now well recognized. A spectrum of renal involvement ranging from glomerular thrombosis to renal infarction has been described. A case of systemic lupus erythematosus with immunoglobulin G and M antiphospholipid/anticardiolipin antibodies is reported. The patient developed catastrophic thrombosis in multiple organs, and glomerular thrombosis was documented by renal biopsy. The patient had an acquired antithrombin III deficiency, and the combination of secondary antiphospholipid syndrome with accompanying antithrombin III deficiency predisposed to thrombosis. Several mechanisms by which antiphospholipid/anticardiolipin antibodies cause thrombosis have been proposed and are briefly reviewed.
Matrix Metalloproteinase Activity, Bone Matrix Turnover, and Tumor Cell Proliferation in Prostate Cancer Bone Metastasis
Authors: Jeffrey A. Nemeth, Rafid Yousif, Michael Herzog, Mingxin Che, Jyoti Upadhyay, Bijan Shekarriz, Sunita Bhagat, Chadwick Mullins, Rafael Fridman, Michael L. Cher
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: The metastasis of prostate cancer to bone is associated with a substantial increase in bone matrix turnover. Matrix metalloproteinases (MMPs) play roles in both normal bone remodeling and invasion and metastasis of prostate cancer. This study was designed to determine the role of MMP activity in prostate cancer that has metastasized to bone. Methods: Single human fetal bone fragments were implanted subcutaneously in immunodeficient mice. Four weeks later, PC3 human prostate cancer cells were injected directly into some of the implants, and daily treatment was begun with batimastat (a broad-spectrum MMP inhibitor). There were six mice (i.e., six implants) in each of four experimental arms: bone alone with and without batimastat and bone injected with PC3 cells with and without batimastat. Bone implants were harvested after 14 days of treatment and analyzed for MMP expression, bone histomorphometry, osteoclast counts, blood vessel density, and tumor cell proliferation and apoptosis. Complementary data were obtained from bone biopsy samples from patients and a bone organ coculture system. All statistical tests were two-sided. Results: MMPs were detected in tumor and stromal cells of clinical specimens and experimental bone implants. In vivo, MMP inhibition reduced the number of osteoclasts per millimeter in PC3-injected implants—from 8.2 (95% confidence interval [CI] = 7.9 to 8.5) to 3.0 (95% CI = 2.3 to 3.7) (P = .006). In addition, it prevented degradation of marrow trabeculae within the bone implants (cross-sectional area of implant occupied by mineralized trabeculae: untreated implant = 29.1% [95% CI = 27.1% to 31.1%], PC3-injected implant = 14.0% [95% CI = 10.9% to 17.1%] [P = .005 versus untreated], and batimastat-treated PC3-injected implant = 27.2% [95% CI = 22.4% to 32.0%] [P = .03 versus PC3 injected alone]). MMP inhibition reduced proliferating tumor cells from 20.8% (95% CI = 19.9% to 21.7%) to 7.4% (95% CI = 5.2% to 9.6%) (P = .006), without affecting angiogenesis or apoptosis. In vitro, MMP inhibition had no toxic effect on PC3 cells but prevented calcium release from bone fragments cocultured with PC3 cells. Conclusions: MMP activity appears to play an important role in bone matrix turnover when prostate cancer cells are present in bone. Bone matrix turnover and metastatic tumor growth appear to be involved in a mutually supportive cycle that is disrupted by MMP inhibition.
Peripheral Blood Mononuclear Cell Proliferation to Heat Shock Protein–70 Derived from Autologous Lung Carcinoma
Authors: Alain Michils, Dominique Dutry, Valérie Zegers de Beyl, Myriam Remmelink, Viviane de Maertelaer, Pierre Rocmans
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

In animals, tumor-derived heat shock proteins (HSP) induce immune-mediated protection against autologous cancer. We investigated whether HSP-70 derived from human lung carcinoma are also complexed to tumor-specific antigens. Peripheral blood mononuclear cells collected 10 days after surgery from patients with lung cancer were stimulated with HSP-70 purified from autologous and heterologous tumors. The stimulation index (SI) obtained when stimulating cells with autologous tumor-derived HSP-70 averaged 3.07 +/- 0.75 in patients with lung cancer and 1.57 +/- 0.33 in control subjects (p < 0.001 by analysis of variance). No significant stimulation was observed with HSP-70 derived either from the majority of heterologous tumors or from autologous tumor-free lung tissue. SI decreased from 3.59 +/- 0.65 to 1.65 +/- 0.38 in six patients tested again 3 months after surgery (p = 0.02 by Wilcoxon test for paired data). HSP-70 derived from lung carcinoma are shown to be associated with T cell antigens. The T cell reactivity appears transient and restricted to antigens complexed to HSP-70 derived from autologous tumors only. This suggests that the antigenicity of human lung tumors is unique, which may be crucial for the design of new vaccines.
The Public Health and Economic Benefits of Taxing Sugar-Sweetened Beverages
Authors: Kelly D. Brownell, Thomas Farley, Walter C. Willett, Barry M. Popkin, Frank J. Chaloupka, Joseph W. Thompson, David S. Ludwig
Journal: New England Journal of Medicine (2009)

Consumption of sugar-sweetened beverages has increased in recent decades; evidence suggests that consumption of these beverages contributes to obesity and adverse health outcomes. The authors discuss the potential public health and economic benefits of taxing sugar-sweetened beverages.
Macrophage-Mediated In Vitro Sensitization of T-Lymphocytes. I. Detection of Murine Leukemia Virus-Associated Antigens2
Authors: Abraham J. Treves, Michael Feldman, Henry S. Kaplan
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Macrophage-Mediated In Vitro Sensitization of T-Lymphocytes. I. Detection of Murine Leukemia Virus-Associated Antigens Get access Abraham J. Treves, Abraham J. Treves Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Feldman, Michael Feldman Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry S. Kaplan Henry S. Kaplan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 5, May 1977, Pages 1527–1529, https://doi.org/10.1093/jnci/58.5.1527 Published: 01 May 1977 Article history Received: 30 August 1976 Accepted: 01 November 1976 Published: 01 May 1977
Differences in the expression of pemphigus antigens during epidermal differentiation
Authors: K. IWATSUKI, H. HARADA, R. YOKOTE, F. KANEKO
Journal: British Journal of Dermatology (1995)

Journal Article Differences in the expression of pemphigus antigens during epidermal differentiation Get access K. IWATSUKI, K. IWATSUKI Department of Dermatology, Fukushima Medical College, 1‐Hikarigaoka, Fukushima 960‐12, Japan Search for other works by this author on: Oxford Academic Google Scholar H. HARADA, H. HARADA Department of Dermatology, Fukushima Medical College, 1‐Hikarigaoka, Fukushima 960‐12, Japan Search for other works by this author on: Oxford Academic Google Scholar R. YOKOTE, R. YOKOTE Department of Dermatology, Hamatnatsu University School of Medicine, Hamantatsu, japan Search for other works by this author on: Oxford Academic Google Scholar F. KANEKO F. KANEKO Department of Dermatology, Fukushima Medical College, 1‐Hikarigaoka, Fukushima 960‐12, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 2, 1 August 1995, Pages 209–216, https://doi.org/10.1111/j.1365-2133.1995.tb02617.x Published: 01 August 1995 Article history Accepted: 14 September 1994 Published: 01 August 1995
Comparative analysis of human and bovine papillomaviruses.
Authors: S Karlin, G Ghandour, D E Foulser, L J Korn
Journal: Molecular Biology and Evolution (1984)

A method is presented for the analysis and comparison of nucleic acid and protein sequences utilizing all identity blocks (the term "identity block" refers to a set of consecutive matches between two sequences) above a prescribed length. Moreover, such identity blocks are determined for various groupings of amino acids according to chemical, functional, charge, and hydrophobic classifications. Alignment maps based on these classifications and containing all statistically significant identity blocks between two or more sequences are constructed. New theoretical results for determining the expected length of the longest identity block between sequences are also presented and are used, along with permutation procedures, to ascertain the significance of sequence identity blocks. As an example of the type of information that can be obtained, comparison has been made of the complete DNA sequences and the E1, E2, L1, and L2 genes of human and bovine papillomaviruses based on the classification schemes described above.