tbuckley/cabot-search huggingface dataset:
Enhanced sensitivity to hypoxia-induced diastolic dysfunction in pressure-overload left ventricular hypertrophy in the rat: role of high-energy phosphate depletion.
Authors: L F Wexler, B H Lorell, S Momomura, E O Weinberg, J S Ingwall, C S Apstein
Journal: Circulation Research (1988)

Isolated buffer-perfused rat hearts with pressure-overload hypertrophy develop a greater decrease in left ventricular (LV) diastolic distensibility and a greater impairment in extent of LV relaxation in response to hypoxia than do normal hearts. Using 31P-NMR spectroscopy, we tested the hypothesis that the enhanced susceptibility of hypertrophied hearts to develop hypoxia-induced diastolic dysfunction is due to an accelerated rate of ATP and/or creatine phosphate depletion. Twelve minutes of hypoxia were imposed on isolated isovolumic (balloon-in-left-ventricle) buffer-perfused hearts from 14 rats with pressure-overload hypertrophy (LVH; LV/body wt ratio = 3.43 +/- 17) secondary to hypertension induced by uninephrectomy plus deoxycorticosterone and salt treatment and from 17 age-matched controls (LV/body wt ratio = 2.22 +/- 0.12, p less than 0.001). Coronary artery flow per gram left ventricle was matched in the LVH and control groups during baseline oxygenated conditions and held constant thereafter. Balloon volume was held constant throughout the experiment so that an increase in LV end-diastolic pressure during hypoxia represented a decrease in LV diastolic distensibility. LV systolic pressure was 165 +/- 9 mm Hg in the LVH group compared with 120 +/- 5 mm Hg in the controls during baseline aerobic perfusion (p less than 0.001). LV end-diastolic pressure rose significantly more in response to 12 minutes of hypoxia in the LVH group (12 +/- 1 to 44 +/- 10 mm Hg) than in the controls (12 +/- 1 to 20 +/- 3 mm Hg, p = 0.04). During baseline aerobic conditions, ATP content was the same in the LVH (17.1 +/- 0.5 mumol/g dry LV wt, n = 4) and control (18.8 +/- 0.6 mumol/g dry LV wt, n = 4, p = NS) groups. During hypoxia, ATP declined at the same rate in the LVH and control groups (3.2 +/- 0.5 versus 3.0 +/- 0.5%/min, p = NS) despite the greater rise in end-diastolic pressure in the LVH group. Creatine phosphate content during baseline aerobic perfusion was 14% lower in the LVH group compared with controls, but the rate of creatine phosphate depletion during 12 minutes of hypoxia was the same. During hypoxia, intracellular pH declined modestly and to the same degree in both groups. Thus, the greater susceptibility to hypoxia-induced diastolic dysfunction observed in isolated buffer-perfused hypertrophied rat hearts cannot be explained by an initially lower total ATP content or by an accelerated rate of decline of ATP or creatine phosphate.(ABSTRACT TRUNCATED AT 400 WORDS)
Clonal heterogeneity in the functional requirement for Lyt-2/3 molecules on cytolytic T lymphocytes: analysis by antibody blocking and selective trypsinization.
Authors: H R MacDonald, A L Glasebrook, J C Cerottini
Journal: The Journal of Experimental Medicine (1982)

While it is well established that murine cytolytic T lymphocytes (CTL) express the Lyt-2/3 molecular complex on their surface, conflicting results have been reported concerning the role of this complex in CTL activity. In the present study this question was reinvestigated at the clonal level. Although different (H-2b anti-H-2d) CTL clones expressed comparable amounts of Lyt-2/3 molecules, as assessed by quantitative flow microfluorometry, the activity of some clones was inhibited by low doses (10 ng) of monoclonal anti-Lyt-2 or anti-Lyt-3 antibodies (in the absence of complement), whereas other clones were not inhibited by either antibody at doses as high as 5 microgram. Treatment of these clones with doses of trypsin sufficient to cleave Lyt-2/3 antigenic determinants from the cell surface resulted in a similar dissociation: clones that were inhibited by antibodies lost cytolytic activity, whereas "uninhibited" clones were unaffected by trypsin treatment. Moreover, the dissociation observed among different alloreactive clones could be demonstrated with self-H-2-restricted (H-2b anti-MSV) clones exhibiting cross-reactivity with normal H-2d products. The lytic activity of these clones against the relevant syngeneic target cells was unaffected by anti-Lyt-2 antibodies or trypsin, whereas their cross-reactivity on H-2d target cells was abolished by either treatment. These results provide direct evidence for clonal heterogeneity in the requirement for Lyt-2/3 molecules in CTL-mediated lysis. It is proposed that the function of Lyt-2/3 molecules is to stabilize the interaction between CTL receptors and the corresponding antigens on the target cells and that the requirement for such a stabilization is correlated with low number and/or affinity of CTL receptors.
Oncostatin M in combination with tumour necrosis factor induces a chondrocyte membrane associated aggrecanase that is distinct from ADAMTS aggrecanase-1 or -2
Authors: W Hui
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To determine whether oncostatin M (OSM) + tumour necrosis factor α (TNFα) induces aggrecanase activity in chondrocyte membranes, to determine the effects of transforming growth factor β1 (TGFβ1), interleukin 4 (IL4), and tissue inhibitor of metalloproteinases (TIMPs) on this activity, and to determine whether this activity is due to a known ADAMTS aggrecanase. <b>Methods:</b> Aggrecanase activity and ability of agents to prevent membrane associated aggrecanase activity were assessed by Western blotting. Expression of known aggrecanases was measured by real time polymerase chain reaction in bovine nasal and human articular chondrocytes. <b>Results:</b> Chondrocyte membrane associated aggrecanase activity and increased mRNA expression of ADAMTS-1, -4, -5, and -9, but not ADAMTS-4 or -15, were enhanced after stimulation by OSM+TNFα in bovine chondrocytes. This activity was inhibited by TIMP-3. In human chondrocytes, OSM+TNFα also enhanced ADAMTS-1 and -4 expression, but not that of other ADAMTSs. TNFα alone induced ADAMTS-9 expression, whereas OSM addition caused suppression. Both TGFβ1 and IL4 blocked membrane associated aggrecanase activity and decreased OSM+TNFα-induced expression of ADAMTS-9 in bovine and human chondrocytes. IL4 down regulated ADAMTS-4 mRNA, whereas TGFβ1 increased this expression in both bovine and human chondrocytes. <b>Conclusions:</b> OSM+TNFα up regulates membrane associated aggrecanase activity and several ADAMTS aggrecanase mRNAs in chondrocytes. The chondroprotective effects of IL4 and TIMP-3 suggest that they may have therapeutic benefit for aggrecanolysis, whereas the differential inhibitory effects of TGFβ1 may limit its therapeutic potential. Induced membrane associated aggrecanase activity is distinct from known soluble ADAMTS aggrecanases and merits further investigation.
Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression
Authors: Silvia Deaglio, Karen M. Dwyer, Wenda Gao, David Friedman, Anny Usheva, Anna Erat, Jiang-Fan Chen, Keiichii Enjyoji, Joel Linden, Mohamed Oukka, Vijay K. Kuchroo, Terry B. Strom, Simon C. Robson
Journal: The Journal of Experimental Medicine (2007)

The study of T regulatory cells (T reg cells) has been limited by the lack of specific surface markers and an inability to define mechanisms of suppression. We show that the expression of CD39/ENTPD1 in concert with CD73/ecto-5′-nucleotidase distinguishes CD4+/CD25+/Foxp3+ T reg cells from other T cells. These ectoenzymes generate pericellular adenosine from extracellular nucleotides. The coordinated expression of CD39/CD73 on T reg cells and the adenosine A2A receptor on activated T effector cells generates immunosuppressive loops, indicating roles in the inhibitory function of T reg cells. Consequently, T reg cells from Cd39-null mice show impaired suppressive properties in vitro and fail to block allograft rejection in vivo. We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation.
Allergy to limpet
Authors: T. Carrillo, F. R. de Castro, M. Cuevas, J. Caminero, P. Cabrera
Journal: Allergy (1991)

Allergy to mollusk has rarely been described. The limpet, belonging to Phylum mollusca , is one of the most frequent mollusks in the Canary Islands, as in all warm maritime regions. We report two cases of atopic patients who developed anaphylactic reactions alter ingestion of this mollusk. Type I hypersensitivity to limpet antigens was demonstrated by means of immediate skin test reactivity, specific IgE determination by RAST, and histamine release test to cooked limpet extract. The controls did not react to any of these tests. Allergic activity was only found with a cooked limpet extract; this suggests that tile offending antigen/s may have been released by cooking this food.
FACTITIOUS WEALING AT THE SITE OF PREVIOUS CUTANEOUS RESPONSE
Authors: JEAN JAMES, ROBERT P. WARIN
Journal: British Journal of Dermatology (1969)

Journal Article FACTITIOUS WEALING AT THE SITE OF PREVIOUS CUTANEOUS RESPONSE Get access JEAN JAMES, JEAN JAMES Department of Dermatology, General Hospital, Bristol Search for other works by this author on: Oxford Academic Google Scholar ROBERT P. WARIN ROBERT P. WARIN Department of Dermatology, General Hospital, Bristol Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 12, 1 December 1969, Pages 882–884, https://doi.org/10.1111/j.1365-2133.1969.tb15968.x Published: 01 December 1969 Article history Accepted: 23 May 1969 Published: 01 December 1969
Intrahepatic Mrna Expression of Interferon–Inducible Antiviral Genes in Liver Diseases: Dsrna–Dependent Protein Kinase Overexpression and Rnase L Inhibitor Suppression in Chronic Hepatitis C
Authors: Shin-Han Yu, Kazuyoshi Nagayama, Nobuyuki Enomoto, Namiki Izumi, Fumiaki Marumo, Chifumi Sato
Journal: Hepatology (2000)

As a part of the defense mechanism of the host to viral infection, interferons induce the transcription of several genes. These interferon-inducible genes contribute to the eradication of the viruses. Whereas some studies suggested the participation of a dsRNA-dependent protein kinase in the host reaction to hepatitis C virus infection, the involvement of other interferon-inducible genes has not been evaluated. Furthermore, there has been no analysis on the expression profile of multiple interferon-inducible genes. The aim of this study was to clarify the hepatic mRNA expression profile of interferon-inducible genes with a special concern to chronic hepatitis C. A total of 76 liver biopsy samples (28 with chronic hepatitis C, 10 with chronic hepatitis B, 9 with alcoholic liver disease, 14 with autoimmune hepatitis, 10 with primary biliary cirrhosis, and 5 of normal liver) were enrolled. The expression of the following genes was quantified by competitive reverse transcription-polymerase chain reaction and was compared according to the etiology; dsRNA-dependent protein kinase (PKR), 2',5'-oligoadenylate synthetase (2,5-AS), latent cellular endoribonuclease (RNase L), RNase L inhibitor, and MxA. As a result, PKR mRNA was significantly overexpressed in the liver of chronic hepatitis C compared with those of other etiologies (P =.0178), and it correlated significantly with serum alanine transaminase values (r =.51, P =.0054). Also, the expression of the RNase L inhibitor showed a significant reduction in chronic hepatitis C (P =.0184). The expressions of 2,5-AS, RNase L, and MxA were not different significantly irrespective to the etiology. In conclusion, hepatic overexpression of PKR and reduced expression of RNase L inhibitor seem to contribute to the anti-HCV mechanism characteristically.
Breast Cancer Following Radiotherapy and Chemotherapy Among Young Women With Hodgkin Disease
Authors: Lois B. Travis, Deirdre A. Hill, Graça M. Dores, Mary Gospodarowicz, Flora E. van Leeuwen, Eric Holowaty, Bengt Glimelius, Michael Andersson, Tom Wiklund, Charles F. Lynch, Mars B. Van't Veer, Ingrid Glimelius, Hans Storm, Eero Pukkala, Marilyn Stovall, Rochelle Curtis, John D. Boice, Ethel Gilbert
Journal: JAMA (2003)

<h3>Context</h3> Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk. <h3>Objective</h3> To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD. <h3>Design, Setting, and Subjects</h3> Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998. <h3>Main Outcome Measures</h3> Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents. <h3>Results</h3> Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (<i>P</i>&lt;.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5;<i>P</i>= .03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (<i>P</i>= .003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses. <h3>Conclusions</h3> Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.
Improvement of Postnatal Neovascularization by Human Adipose Tissue-Derived Stem Cells
Authors: A. Miranville, C. Heeschen, C. Sengenès, C.A. Curat, R. Busse, A. Bouloumié
Journal: Circulation (2004)

Background— Several studies have suggested that stem cells are present in the stroma-vascular fraction (SVF) of adipose tissue (AT). Methods and Results— To characterize the cell populations that compose the SVF of human AT originating from subcutaneous and visceral depots, fluorescence-activated cell sorter analysis was performed by use of fluorescent antibodies directed against the endothelial and stem cell markers CD31, CD34, CD133, and ABCG2. The freshly harvested SVF contained large numbers of CD34 + cells as well as cells expressing CD133 and ABCG2. Further analysis of the CD34 + cells revealed 2 CD34 + cell populations with differential expression of the endothelial cell marker CD31. Selection of the CD34 + /CD31 − cells by use of magnetic microbeads, followed by cell culture, demonstrated that this cell population could differentiate under appropriate conditions into endothelial cells. Moreover, in mouse ischemic hindlimb, intravenous injection of CD34 + /CD31 − cells was associated with an increase in the blood flow and the capillary density and an incorporation of the cells in the leg vasculature. Conclusions— Our data indicate the presence of a cell population within the SVF of human AT characterized as CD34 + /CD31 − exhibiting characteristics of endothelial progenitor cells. Therefore, human AT might represent a source of stem/progenitor cells useful for cell therapy to improve vasculogenesis in adults.
Inhibition of Neovascularization to Simultaneously Ameliorate Graft-vs-Host Disease and Decrease Tumor Growth
Authors: Olaf Penack, Erik Henke, David Suh, Chris G. King, Odette M. Smith, Il-Kang Na, Amanda M. Holland, Arnab Ghosh, Sydney X. Lu, Robert R. Jenq, Chen Liu, George F. Murphy, Theresa T. Lu, Chad May, David A. Scheinberg, Ding Cheng Gao, Vivek Mittal, Glenn Heller, Robert Benezra, Marcel R. M. van den Brink
Journal: JNCI Journal of the National Cancer Institute (2010)

BACKGROUND Blood vessels are formed either by sprouting of resident tissue endothelial cells (angiogenesis) or by recruitment of bone marrow (BM)-derived circulating endothelial progenitor cells (EPCs, vasculogenesis). Neovascularization has been implicated in tumor growth and inflammation, but its roles in graft-vs-host disease (GVHD) and in tumors after allogeneic BM transplantation (allo-BMT) were not known. METHODS We analyzed neovascularization, the contribution of endothelial cells and EPCs, and the ability of anti-vascular endothelial-cadherin antibody, E4G10, to inhibit neovascularization in mice with GVHD after allo-BMT using immunofluorescence microscopy and flow cytometry. We examined survival and clinical and histopathologic GVHD in mice (n = 10-25 per group) in which GVHD was treated with the E4G10 antibody using immunohistochemistry, flow cytometry, and cytokine immunoassay. We also assessed survival, the contribution of green fluorescent protein-marked EPCs to the tumor vasculature, and the ability of E4G10 to inhibit tumor growth in tumor-bearing mice (n = 20-33 per group) after allo-BMT using histopathology and bioluminescence imaging. All statistical tests were two-sided. RESULTS We found increased neovascularization mediated by vasculogenesis, as opposed to angiogenesis, in GVHD target tissues, such as liver and intestines. Administration of E4G10 inhibited neovascularization by donor BM-derived cells without affecting host vascularization, inhibited both GVHD and tumor growth, and increased survival (at 60 days post-BMT and tumor challenge with A20 lymphoma, the probability of survival was 0.29 for control antibody-treated allo-BMT recipients vs 0.7 for E4G10-treated allo-BMT recipients, 95% confidence interval = 0.180 to 0.640, P < .001). CONCLUSIONS Therapeutic targeting of neovascularization in allo-BMT recipients is a novel strategy to simultaneously ameliorate GVHD and inhibit posttransplant tumor growth, providing a new approach to improve the overall outcome of allogeneic hematopoietic stem cell transplantation.
Subcutaneous Enoxaparin Once or Twice Daily Compared with Intravenous Unfractionated Heparin for Treatment of Venous Thromboembolic Disease
Authors: Geno Merli
Journal: Annals of Internal Medicine (2001)

Background: Low-molecular-weight heparins administered subcutaneously once or twice daily have been reported to be as safe and efficacious as intravenous unfractionated heparin in the treatment of acute venous thromboembolic disease. Objective: To determine whether subcutaneous enoxaparin administered once or twice daily is as effective as continuously infused unfractionated heparin in acute symptomatic venous thromboembolic disease. Design: Randomized, controlled, partially blinded equivalence trial. Setting: 74 hospitals in 16 countries. Patients: 900 patients with symptomatic lower-extremity deep venous thrombosis, including 287 (32%) with confirmed pulmonary embolism. Interventions: Initial therapy with dose-adjusted intravenous unfractionated heparin compared with subcutaneous enoxaparin at fixed dosages of 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily. Long-term oral anticoagulation was started in all patients within 72 hours of randomization. Measurements: Clinical end points assessed during a 3-month follow-up period. Results: Equivalent efficacy was seen in the heparin group and both enoxaparin groups. Symptomatic venous thromboembolism recurred in 12 of 290 patients receiving unfractionated heparin (4.1%), 13 of 298 patients receiving once-daily enoxaparin (4.4%), and 9 of 312 patients receiving twice-daily enoxaparin (2.9%). Compared with unfractionated heparin, the treatment difference was 0.2% (95% CI, −3.04% to 3.49%) for once-daily enoxaparin and −1.2% (CI, −4.2% to 1.7%) for twice-daily enoxaparin. Incidence of major hemorrhage did not differ among the three treatment groups. Major hemorrhage occurred in 6 of 290 patients (2.1%) in the unfractionated heparin group, 5 of 298 patients (1.7%) in the once-daily enoxaparin group, and 4 of 312 patients (1.3%) in the twice-daily enoxaparin group. Conclusions: Subcutaneous enoxaparin once or twice daily is as effective and safe as dose-adjusted, continuously infused unfractionated heparin in the prevention of recurrent symptomatic venous thromboembolic disease. *For members of the Enoxaparin Clinical Trial Group and other study participants, see Appendix.
Regeneration of the Infarcted Heart With Stem Cells Derived by Nuclear Transplantation
Authors: Robert Lanza, Malcolm A.S. Moore, Teruhiko Wakayama, Anthony C.F. Perry, Jae-Hung Shieh, Jan Hendrikx, Annarosa Leri, Stefano Chimenti, Alyssa Monsen, Daria Nurzynska, Michael D. West, Jan Kajstura, Piero Anversa
Journal: Circulation Research (2004)

Nuclear transfer techniques have been proposed as a strategy for generating an unlimited supply of rejuvenated and histocompatible stem cells for the treatment of cardiac diseases. For this purpose, c-kit-positive fetal liver stem cells obtained from cloned embryos were injected in the border zone of infarcted mice to induce tissue reconstitution. Cloned embryos were derived from somatic cell fusion between nuclei of cultured LacZ-positive fibroblasts and enucleated oocytes of a different mouse strain. We report that regenerating myocardium replaced 38% of the scar at 1 month. The rebuilt tissue expressed LacZ and was composed of myocytes and vessels connected with the coronary circulation. Myocytes were functionally competent and expressed contractile proteins, desmin, connexin43, and N-cadherin. These structural characteristics indicated that the new myocytes were electrically and mechanically coupled. Similarly, the formed coronary arterioles and capillary structures contained blood and contributed, therefore, to tissue oxygenation. Cardiac replacement resulted in an improvement of ventricular hemodynamics and in a reduction of diastolic wall stress. These beneficial effects were obtained by stem cell transdifferentiation and commitment to the cardiac cell lineages. Myocardial growth was independent from fusion of the injected stem cells with preexisting partner cells. In conclusion, c-kit-positive stem cells derived by nuclear transfer cloning restore infarcted myocardium. Although problems currently plague nuclear transplantation, including the potential for epigenetic and imprinting abnormalities, stem cells derived from cloned embryos are sufficiently normal to repair damaged tissue in vivo. Importantly, the magnitude of myocardial regeneration obtained in this study is significantly superior to that achieved with adult bone marrow cells.