tbuckley/cabot-search huggingface dataset:
EFFECTIVENESS OF TRANSFUSIONS OF FRESH AND LYOPHILIZED PLATELETS IN CONTROLLING BLEEDING DUE TO THROMBOCYTOPENIA*
Authors: Dudley P. Jackson, Dale K. Sorensen, Eugene P. Cronkite, Victor P. Bond, Theodore M. Fliedner
Journal: Journal of Clinical Investigation (1959)

lated in recipients suppressed the number of red blood cells in thoracic duct lymph of irradiated dogs (8). In the present studies, the effectiveness of lyophilized platelets was compared with the effectiveness of fresh platelets in suppressing the number of red blood cells in the thoracic duct lymph of irradiated dogs.
Unrecognized Myocardial Infarction: Epidemiology, Clinical Characteristics, and the Prognostic Role of Angina Pectoris: The Reykjavik Study
Authors: Emil Sigurdsson
Journal: Annals of Internal Medicine (1995)

Objective: To evaluate the incidence, prevalence, characteristics, and prognosis associated with clinically unrecognized myocardial infarction as diagnosed by electrocardiographic changes. Design: Prospective, population-based cohort study with 4-to 20-year follow-up. Setting: Icelandic Heart Association Preventive Clinic. Participants: 9141 men residing in the Reykjavik area who were born between 1907 and 1934. Measurements: Patients were assigned to categories of coronary heart disease at first visit on the basis of hospital records, Rose chest pain questionnaire, standardized 12-lead electrocardiogram, and history and physical examination. Incidence and prevalence of unrecognized myocardial infarction were determined, survival was measured, and causes of death were deter-mined from death certificates and autopsy records. Results: Prevalence was strongly influenced by age. Nearly undetectable in the youngest age group, it increased to more than 5% in the group aged 75 to 79 years. Incidence was almost zero up to age 40, then increased steeply to more than 300 cases per year per 100 000 persons at age 60, and decreased with age after age 65. Ten- and 15-year survival probabilities were 51% and 45%, respectively, and were similar to those for patients with recognized myocardial infarction. One third of men with unrecognized and 58% of men with recognized myocardial infarction had a history of angina pectoris (P < 0.001). Angina pectoris had a greater effect on coronary heart disease mortality in the former group than in the latter. The risk ratio for unrecognized myocardial infarction was 4.6 without angina (95% CI, 2.4 to 8.6) and 16.9 with angina (CI, 9.4 to 30.3); the risk ratio for recognized myocardial infarction was 6.3 without angina (CI, 3.7 to 10.6) and 8.5 with angina (CI, 5.8 to 12.6). Conclusion: At least one third of all myocardial infarctions were unrecognized. Prognosis and risk factor profiles for patients with recognized and unrecognized myocardial infarction were similar. Although those with unrecognized myocardial infarction were less likely than those with recognized myocardial infarction to have a history of angina pectoris, angina in these cases was usually associated with ischemic electrocardiographic changes and a poor prognosis, suggesting severe coronary heart disease.
Maintenance therapy with ribavirin in patients with chronic hepatitis C who fail to respond to combination therapy with interferon alfa and ribavirin
Authors: Jay H. Hoofnagle, Marc G. Ghany, David E. Kleiner, Edward Doo, Theo Heller, Kittichai Promrat, Janus Ong, Farooq Khokhar, Alejandro Soza, David Herion, Yoon Park, James E. Everhart, Jake T. Liang
Journal: Hepatology (2003)

To assess the efficacy and safety of maintenance therapy with ribavirin alone in chronic hepatitis C, 108 patients were treated with the combination of interferon alfa and ribavirin for 24 weeks; those who failed to have a virologic response were offered enrollment in a randomized, double-blind, controlled trial of ribavirin (1,000-1,200 mg daily) versus placebo for the subsequent 48 weeks. Patients were monitored at regular intervals with symptom questionnaires, serum aminotransferase levels, hepatitis C virus (HCV) RNA levels, and complete blood counts and underwent liver biopsy at the completion of therapy. Among 108 patients, 50 were still HCV RNA positive after 24 weeks of treatment, of whom 34 agreed to be randomized to continue either ribavirin monotherapy or placebo. Among 17 patients who received placebo, there was no overall improvement in symptoms, serum alanine aminotransferase (ALT) levels, HCV RNA levels, or hepatic histology. Among the 17 patients who received ribavirin, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels, and hepatic fibrosis scores were not changed significantly from baseline. Responses to ribavirin seemed to be categorical, such that 8 patients (47%) had definite improvement in liver histology. Patients with improved histology had improvements in serum ALT levels both on combination therapy and after switching to ribavirin monotherapy. In conclusion, continuation of ribavirin monotherapy may maintain serum biochemical improvements that occur during interferon-ribavirin combination therapy in some patients and that these improvements are often associated with decreases in necroinflammatory changes in the liver. Whether these improvements will ultimately result in prevention of progression of hepatitis C requires further study.
Matrix Metalloproteinase Inhibition During the Development of Congestive Heart Failure
Authors: Francis G. Spinale, Mytsi L. Coker, Stephen R. Krombach, Rupak Mukherjee, Hussein Hallak, Ward V. Houck, Mark J. Clair, Scott B. Kribbs, Linda L. Johnson, J. Thomas Peterson, Michael R. Zile
Journal: Circulation Research (1999)

Abstract —The development of congestive heart failure (CHF) is associated with left ventricle (LV) dilation and myocardial remodeling. The matrix metalloproteinases (MMPs) play a significant role in extracellular remodeling, and recent studies have demonstrated increased MMP expression and activity with CHF. Whether increased MMP activity directly contributes to the LV remodeling with CHF remains unknown. Accordingly, this study examined the effects of chronic MMP inhibition (MMPi) on LV size and function during the progression of CHF. Pigs were assigned to the following groups: (1) CHF, rapid pacing for 3 weeks at 240 bpm (n=12); (2) CHF/MMPi, rapid pacing and concomitant MMPi (PD166793, 20 mg/kg per day [n=10]), and (3) control (n=11). With pacing CHF, LV fractional shortening was reduced (19±1 versus 45±1%), and end-diastolic dimension increased (5.67±0.11 versus 3.55±0.05 cm), compared with baseline values ( P &lt;0.05). In the CHF/MMPi group, LV endocardial shortening increased (25±2%) and the end-diastolic dimension was reduced (4.92±0.17 cm) compared with CHF-only values ( P &lt;0.05). LV midwall shortening was reduced to a comparable degree in the CHF-only and CHF/MMPi groups. LV peak wall stress increased 3-fold with pacing CHF compared with controls and was significantly reduced in the CHF/MMPi group. LV myocardial stiffness was unchanged with CHF but was increased in the CHF/MMPi group. LV myocyte length was increased with pacing CHF compared with controls (180±3 versus 125±4 μm, P &lt;0.05) and was reduced in the CHF/MMPi group (169±4 μm, P &lt;0.05). Basal-state myocyte shortening velocity was reduced with pacing CHF compared with controls (33±2 versus 66±1 μm/s, P &lt;0.05) and was unchanged in the CHF/MMPi group (31±2 μm/s). Using an ex vivo assay system, myocardial MMP activity was increased with pacing CHF and was reduced with chronic MMPi. In summary, concomitant MMPi with developing CHF limited LV dilation and reduced wall stress. These results suggest that increased myocardial MMP activity contributes to LV myocardial remodeling in developing CHF.
Life (and death) in the Fas lane
Authors: A N AKBAR
Journal: Gut (1998)

See article on page48 

The hallmark of an immune response is the generation of a large new cohort of specific lymphocytes dedicated to the removal of the stimulating antigen. The protection afforded by the mobilisation of an army of potentially destructive cells comes at a price as these cells, if uncontrolled, may turn on the host. Thus when excessive immune activity occurs, immunopathology resulting from the “friendly fire” of inflammatory cells may compromise healthy tissue. To safeguard against this, mechanisms have evolved that remove the expanded population of leucocytes both at the end of the immune response, when antigen is eradicated, and also when excessive activation may be taking place.1 The ligation of a surface membrane molecule CD95 (Fas/Apo-1) on activated T cells by its ligand leads to apoptosis.2 Although once activated, the expression of the CD95 receptor is stable, …
Ancillary Benefits for Climate Change Mitigation and Air Pollution Control in the World's Motor Vehicle Fleets
Authors: Michael P. Walsh
Journal: Annual Review of Public Health (2008)

The global motor vehicle population has grown very rapidly in the past half century and is expected to continue to grow rapidly for the next several decades, especially in developing countries. As a result, vehicles are a major source of urban air pollution in many cities and are the fastest-growing source of greenhouse emissions. Strategies exist to reduce both problems, but many countries emphasize one over the other rather than pursuing strategies that reduce both concerns. Using diesel as an example, this article illustrates that it is now possible not only to reduce carbon dioxide with the increased use of diesel vehicles but also to improve urban air pollution. Doing so requires both stringent emissions regulations and clean fuels. Several principles contained in the Bellagio Memorandum are highlighted as guides for policy makers.
The role of smoking in development of endothelial dysfunction in patients with COPD in combination with AH
Authors: Oxana Belina, Natalia Shaporova, Maria Menshutina, Vera Achkasova, Olga Galkina, Margarita Kadinskaya, Vera Didur
Journal: European Respiratory Journal (2011)

Endothelial dysfunction (ED) is a pathological finding of COPD and arterial hypertension (AH) at different stages.Incidence of AH in patients with COPD is higher than in the population.The important risk factor of COPD and AH is smoking which may initiate vascular impairment by stimulate adhesion molecule expression and leukocyte adhesion to endothelium.

Aims: The purpose of study was to find out the role of ED in the pathogenesis of COPD in combination with AH using sVCAM-1, and to study the reversibility of changes in the endothelium after smoking cessation.

Methods: Plasma levels of sVCAM-1 were quantified by ELISA in age-matched 45 patients with COPD and AH (mean age 61±6,5) that were either current smoking COPD patients with AH (n=12) and COPD ex-smokers with AH (n=12),to be compared with smokers (n=10) and nonsmokers with AH (n=11).

Results: The comparison of smoking (19.5±4.8) and ex-smoking (15.5±3.6) COPD patients with AH revealed that level of sVCAM-1 was higher in smokers (p<0.05). There is no difference in smokers with AH (14.7±5.4) comparing with non-smokers (16.5±4.7). We have found difference between smokers with COPD and AH and smokers with AH (p<0.05), and a correlation between sVCAM-1 plasma level and the age (r=0.46,p<0.05).

Conclusions: Our results show that COPD smokers with AH have more evident expression of adhesion molecule to endothelium to be compared with ex-smokers. The combination of COPD and AH has more evident contribution in development of ED.The less evident of ED in ex-smoking patients shows reversibility of these changes.Correlation between sVCAM-1 and age shows that ED in elderly patients plays important pathogenetic role in comparing with middle age patients.
Problems in Management of Acute Myocardial Infarction
Authors: A. R. Gilchrist
Journal: BMJ (1960)

Acute myocardial infarction varies greatly in severity from patient to patient.Its course is treacherous, its complications are frequent and serious, and its super- vision is often testing and exacting.Five aspects of the medical management of these patients are worthy of special consideration in the light of current experience.1. Diagnosis Successful management depends primarily on early and precise diagnosis.The illness can theni be more accurately assessed, the probability of complications more readily anticipated, and appropriate therapy begun from the outset.The first problem is the necessity to establish the diagnosis accurately and early.In assuming responsibility for the management of acute myocardial inf*arctioni, the doctor should not hesitate to enlist the diagnostic help which technical procedures can provide.Many conditions masquerade as myocardial infarction.Electrocardiograms and other tests-transaminase levels, sedimentation rates are not infallible, but in the hands of experienced observers they can provide a standard of accuracy of diagnosis with which the unaided clinician cannot compete.Paton (1957), working in this hospital, had a 94% accuracy of electrocardiographic diagnosis as judged by post- mortem control.This compared with a 35% accuracy amongst a group of patients in whom death occurred after days or weeks of observation by the physician who elected to place reliance purely on his clinical judgment.without the diagnostic help which electrocardiograms can provide.The moral is obvious. Home or Institutional CareAn early decision must be taken on the advisability of home or institutional care.Routine medical
BMA annual meeting: Doctors vote for an end to competitive tendering
Authors: G. Iacobucci
Journal: BMJ (2014)

Doctors have overwhelmingly called on the UK government to repeal legislation that requires many clinical services in England to be tendered on the open market.

Delegates at the BMA’s Annual Representative Meeting in Harrogate carried a motion that said they were “dismayed that private providers have won so many tenders for clinical services” in the NHS in England since the Health and Social Care Act came into force. The motion called for the repeal of competitive tendering legislation, in favour of a “patient focused healthcare system based on collaboration, cooperation, transparency, and accountability.”

The act introduced new rules expanding the role of competition in the NHS in England. Under the rules, clinical commissioning groups must be able to justify any decision not to …
Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine.
Authors: U von Freeden-Jeffry, P Vieira, L A Lucian, T McNeil, S E Burdach, R Murray
Journal: The Journal of Experimental Medicine (1995)

Interleukin (IL)-7 is a potent stimulus for immature T and B cells and, to a lesser extent, mature T cells. We have inactivated the IL-7 gene in the mouse germline by using gene-targeting techniques to further understand the biology of IL-7. Mutant mice were highly lymphopenic in the peripheral blood and lymphoid organs. Bone marrow B lymphopoiesis was blocked at the transition from pro-B to pre-B cells. Thymic cellularity was reduced 20-fold, but retained normal distribution of CD4 and CD8. Splenic T cellularity was reduced 10-fold. Splenic B cells, also reduced in number, showed an abnormal population of immature B cells in adult animals. The remaining splenic populations of lymphocytes showed normal responsiveness to mitogenic stimuli. These data show that proper T and B cell development is dependent on IL-7. The IL-7-deficient mice are the first example of single cytokine-deficient mice that exhibit severe lymphoid abnormalities.
Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture
Authors: M R Bennett
Journal: Cardiovascular Research (1999)

Apoptosis (programmed cell death) of vascular smooth muscle cells (VSMCs) has recently been identified as an important process in a variety of human vascular diseases, including atherosclerosis, arterial injury, and restenosis after angioplasty. VSMC apoptosis is regulated by interactions between the local cell–cell and cytokine environment within the arterial wall, and the expression of pro- and anti-apoptotic proteins by the cell, including death receptors, proto-oncogenes and tumour suppressor genes. This review summarises our current knowledge of the occurrence and mechanisms underlying VSMC apoptosis in atherosclerosis and arterial remodelling.
Mechanisms of Tamoxifen Resistance: Increased Estrogen Receptor-HER2/neu Cross-Talk in ER/HER2-Positive Breast Cancer
Authors: J. Shou, S. Massarweh, C. K. Osborne, A. E. Wakeling, S. Ali, H. Weiss, R. Schiff
Journal: JNCI Journal of the National Cancer Institute (2004)

Patients receiving adjuvant tamoxifen whose tumors express high levels of both HER2/neu (HER2) and the estrogen receptor (ER) coactivator AIB1 often develop tamoxifen resistance. We used a breast cancer model system with high expression of AIB1 and HER2 to investigate the possible mechanisms underlying this resistance.MCF-7 breast cancer cells, which express high levels of AIB1, and a tamoxifen-resistant derivative cell line engineered to overexpress HER2 (MCF-7/HER2-18) were treated with estrogen, tamoxifen, epidermal growth factor (EGF), or heregulin in the absence or presence of the EGF receptor (EGFR) tyrosine kinase inhibitor gefitinib. We analyzed phosphorylation of signaling intermediates by immunoblotting, ER transcriptional activity with reporter gene constructs and immunoblot analysis of endogenous gene products, promoter assembly by chromatin immunoprecipitation (ChIP) assay, and tumor cell growth in vitro by anchorage-independent colony formation and in vivo using xenografts in nude mice.MCF-7/HER2-18 tumors were completely growth inhibited by estrogen deprivation but were growth stimulated by tamoxifen. Molecular cross-talk between the ER and HER2 pathways was increased in the MCF-7/HER-2 cells compared with MCF-7 cells, with cross-phosphorylation and activation of both the ER and the EGFR/HER2 receptors, the signaling molecules AKT and ERK 1,2 mitogen-activated protein kinase (MAPK), and AIB1 itself with both estrogen and tamoxifen treatment. Tamoxifen recruited coactivator complexes (ER, AIB1, CBP, p300) to the ER-regulated pS2 gene promoter in MCF-7/HER2-18 cells and corepressor complexes (NCoR, histone deacetylase 3) in MCF-7 cells. Gefitinib pretreatment blocked receptor cross-talk, reestablished corepressor complexes with tamoxifen-bound ER on target gene promoters, eliminated tamoxifen's agonist effects, and restored its antitumor activity both in vitro and in vivo in MCF-7/HER2-18 cells.Tamoxifen behaves as an estrogen agonist in breast cancer cells that express high levels of AIB1 and HER2, resulting in de novo resistance. Gefitinib's ability to eliminate this cross-talk and to restore tamoxifen's antitumor effects should be tested in the clinic.
Protein Kinase C Inhibitor Sotrastaurin Selectively Inhibits the Growth of CD79 Mutant Diffuse Large B-Cell Lymphomas
Authors: Tara L. Naylor, Huaping Tang, Boris A. Ratsch, Andreas Enns, Alice Loo, Liqing Chen, Peter Lenz, Nigel J. Waters, Walter Schuler, Bernd Dörken, Yung-mae Yao, Markus Warmuth, Georg Lenz, Frank Stegmeier
Journal: Cancer Research (2011)

The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) correlates with poor prognosis. The ABC subtype of DLBCL is associated with constitutive activation of the NF-κB pathway, and oncogenic lesions have been identified in its regulators, including CARD11/CARMA1 (caspase recruitment domain-containing protein 11), A20/TNFAIP3, and CD79A/B. In this study, we offer evidence of therapeutic potential for the selective PKC (protein kinase C) inhibitor sotrastaurin (STN) in preclinical models of DLBCL. A significant fraction of ABC DLBCL cell lines exhibited strong sensitivity to STN, and we found that the molecular nature of NF-κB pathway lesions predicted responsiveness. CD79A/B mutations correlated with STN sensitivity, whereas CARD11 mutations rendered ABC DLBCL cell lines insensitive. Growth inhibitory effects of PKC inhibition correlated with NF-κB pathway inhibition and were mediated by induction of G₁-phase cell-cycle arrest and/or cell death. We found that STN produced significant antitumor effects in a mouse xenograft model of CD79A/B-mutated DLBCL. Collectively, our findings offer a strong rationale for the clinical evaluation of STN in ABC DLBCL patients who harbor CD79 mutations also illustrating the necessity to stratify DLBCL patients according to their genetic abnormalities.
Pancreatic Disease Towards the Year 2000.
Authors: P G LANKISCH
Journal: Gut (1999)

Pancreatic Disease Towards the Year 2000. 2nd edn. Edited by Johnson CD, Imrie CW. (Pp 468; illustrated; £80.00.) Berlin: Springer Verlag, 1999. ISBN 1-85233-037-6.

This interesting book arises from a series of lectures held at a meeting in Glasgow. The editors have chosen a very ambitious title, Pancreatic Disease towards the Year 2000 , which an impartial reader could interpret in two ways: either the book is a review of all pancreatic diseases or it …
Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging
Authors: T. Utsugi, T. Ohno, Y. Ohyama, T. Uchiyama, Y. Saito, Y. Matsumura, H. Aizawa, H. Itoh, M. Kurabayashi, S. Kawazu, S. Tomono, Y. Oka, T. Suga, M. Kuro-o, Y. Nabeshima, R. Nagai
Journal: Metabolism (2000)
Intrarenal Angiotensin-Converting Enzyme Induces Hypertension in Response to Angiotensin I Infusion
Authors: Romer A. Gonzalez-Villalobos, Sandrine Billet, Catherine Kim, Ryousuke Satou, Sebastien Fuchs, Kenneth E. Bernstein, L. Gabriel Navar
Journal: Journal of the American Society of Nephrology (2010)

The contribution of the intrarenal renin-angiotensin system to the development of hypertension is incompletely understood. Here, we used targeted homologous recombination to generate mice that express angiotensin-converting enzyme (ACE) in the kidney tubules but not in other tissues. Mice homozygous for this genetic modification (ACE 9/9 mice) had low BP levels, impaired ability to concentrate urine, and variable medullary thinning. In accord with the ACE distribution, these mice also had reduced circulating angiotensin II and high plasma renin concentration but maintained normal kidney angiotensin II levels. In response to chronic angiotensin I infusions, ACE 9/9 mice displayed increased kidney angiotensin II, enhanced rate of urinary angiotensin II excretion, and development of hypertension. These findings suggest that intrarenal ACE-derived angiotensin II formation, even in the absence of systemic ACE, increases kidney angiotensin II levels and promotes the development of hypertension.