tbuckley/cabot-search huggingface dataset:
Oxygen and extracellular fluid restriction in cultured heart cells: electron microscopy studies
Authors: Z Ne'eman, A Pinson
Journal: Cardiovascular Research (1990)

Journal Article Oxygen and extracellular fluid restriction in cultured heart cells: electron microscopy studies Get access Zvi Ne'eman, Zvi Ne'eman Correspondence to: Dr Pinson Search for other works by this author on: Oxford Academic PubMed Google Scholar Arié Pinson Arié Pinson Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 7, July 1990, Pages 555–559, https://doi.org/10.1093/cvr/24.7.555 Published: 01 July 1990 Article history Received: 03 January 1990 Accepted: 19 February 1990 Published: 01 July 1990
Respiratory Intensive Care.
Authors: H Pontoppidan, R S Wilson, M A Rie, R C Schneider
Journal: Annals of Internal Medicine (1988)

To surgeons trained before 1970, the techniques, concepts, and vocabulary of respiratory intensive care are frequently bewildering. Even those surgeons trained more recently or house officers now in training could be helped by a guide to the complexities of this field. Dr. Robert M. Rogers, chief of the pulmonary section of the University of Oklahoma, offers such a manual in this collection of essays by contributing authors on the analysis and treatment of the patient in respiratory failure. A number of the chapters appeared in a special issue of CHEST on respiratory intensive care published in August, 1972. Those chapters and others written for this collection give a reasonably complete picture of the management of the moderately or seriously ill patient with respiratory failure. Difficult subjects such as hypercapnia and hypocapnia, acid-base balance, and the physiology and management of hypoxia are attacked in crisp, clear discussions. The beautiful diagrams in a chapter on oxygen transport by Dr. Klocke will aid the uninitiated in understanding this field. Many find working with ventilators confusing. There is a good, full description of ventilator management, including a chapter on positive endexpiratory pressure. Reading this section of the book should clarify the use of respirators considerably, particularly for anyone who at 2:OO a.m. and alone, has wondered how to set the dials on a MA-1. For surgeons, the chapter on pulmonary complications of general surgery by Dr. Pierce should be useful, although the concepts of diffuse microatelectasis and of increased closing volume in the perioperative period (both of which are stressed) are not particularly new. There are good sections on setting up a respiratory intensive care unit and on two procedures (fiberoptic bronchoscopy and bronchopulmonary lavage) used in some patients with failure of gas exchange. As in any multi-authored book, there is some padding and overlap. The proportion here, however, is acceptably low. In general, Respiratory Intensive Care can be recommended as an accurate, clear, and sensible introduction to the subject.
Inhibition of MDM2 attenuates neointimal hyperplasia via suppression of vascular proliferation and inflammation
Authors: Toru Hashimoto, Toshihiro Ichiki, Jiro Ikeda, Eriko Narabayashi, Hirohide Matsuura, Ryohei Miyazaki, Keita Inanaga, Kotaro Takeda, Kenji Sunagawa
Journal: Cardiovascular Research (2011)

Tumour protein p53 plays an important role in the vascular remodelling process as well as in oncogenesis. p53 is negatively regulated by murine double minute 2 (MDM2). A recently developed MDM2 inhibitor, nutlin-3, is a non-genotoxic activator of the p53 pathway. So far, the effect of MDM2 inhibition on vascular remodelling has not been elucidated. We therefore investigated the effect of nutlin-3 on neointima formation. Nutlin-3 up-regulated p53 and its downstream target p21 in vascular smooth muscle cells (VSMCs). DNA synthesis assay and flow cytometric analysis revealed that nutlin-3 inhibited platelet-derived growth factor (PDGF)-induced VSMC proliferation by cell cycle arrest. This inhibitory effect was abrogated in p53-siRNA-transfected VSMCs. Furthermore, nutlin-3 inhibited PDGF-stimulated VSMC migration. Treatment with nutlin-3 attenuated neointimal hyperplasia at 28 days after vascular injury in mice, associated with up-regulation of p53 and p21. BrdU incorporation was decreased at 14 days after injury in nutlin-3-treated mice. TUNEL assay showed that nutlin-3 did not exaggerate apoptosis of the injured vessels. Infiltration of macrophages and T-lymphocytes and mRNA expression of chemokine (C-C motif) ligand-5, interleukin-6, and intercellular adhesion molecule-1 were decreased in the injured vessels of nutlin-3-treated mice. Nutlin-3 suppressed NF-κB activation in VSMCs, but not in p53-siRNA-transfected VSMCs. The MDM2 antagonist nutlin-3 inhibits VSMC proliferation, migration, and NF-κB activation, and also attenuates neointimal hyperplasia after vascular injury in mice, which is associated with suppression of vascular cell proliferation and an inflammatory response. Targeting MDM2 might be a potential therapeutic strategy for the treatment of vascular proliferative diseases.
Off-Label Use of Cancer Drugs: A Benchmark Is Established
Authors: Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2013)

Off-labelprescribing,whichisbroadlydefinedastheprescribing of drugs outside of the marketing authorization determined by a licensing body such as the US Food and Drug Administration, is a controversial issue. On the pro side, off-label prescribing allows individualclinicianstomaketheultimatedecisionastowhetheror notaparticularlicenseddrugisofpotentialbenefittoanindividual patient. There are a number of circumstances in which a physician may be compelled to prescribe off label, some of which may be considered more appropriate than others. Early use of an already licensed drug in a setting that is supported by data from a newly reported randomized study, but that has not yet been vetted through the drug approval process, may be an example of a more appropriateoff-labeluse.Thismaybeparticularlysalientwhenthe approval process is slow, thus limiting access of patients and providers to effective treatments in a timely manner. Additionally, for many cancers, notably rare tumors, there may never be enough evidencetosupportalabelingindicationbecauseoftheinabilityto conduct the appropriate trial as a result of inadequate patient numbers or lack of financial incentives. Not surprisingly, a previous survey found that American oncologists do discuss off-label use with their patients and feel comfortable prescribing for offlabel indications in some circumstances. 1
The Rising Prevalence of Diabetes and Impaired Glucose Tolerance
Authors: David W. Dunstan, Paul Z. Zimmet, Timothy A. Welborn, Maximilian P. de Courten, Adrian J. Cameron, Richard A. Sicree, Terry Dwyer, Stephen Colagiuri, Damien Jolley, Matthew Knuiman, Robert Atkins, Jonathan E. Shaw
Journal: Diabetes Care (2002)

OBJECTIVE—To determine the population-based prevalence of diabetes and other categories of glucose intolerance (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) in Australia and to compare the prevalence with previous Australian data. RESEARCH DESIGN AND METHODS—A national sample involving 11,247 participants aged ≥25 years living in 42 randomly selected areas from the six states and the Northern Territory were examined in a cross-sectional survey using the 75-g oral glucose tolerance test to assess fasting and 2-h plasma glucose concentrations. The World Health Organization diagnostic criteria were used to determine the prevalence of abnormal glucose tolerance. RESULTS—The prevalence of diabetes in Australia was 8.0% in men and 6.8% in women, and an additional 17.4% of men and 15.4% of women had IGT or IFG. Even in the youngest age group (25–34 years), 5.7% of subjects had abnormal glucose tolerance. The overall diabetes prevalence in Australia was 7.4%, and an additional 16.4% had IGT or IFG. Diabetes prevalence has more than doubled since 1981, and this is only partially explained by changes in age profile and obesity. CONCLUSIONS—Australia has a rapidly rising prevalence of diabetes and other categories of abnormal glucose tolerance. The prevalence of abnormal glucose tolerance in Australia is one of the highest yet reported from a developed nation with a predominantly Europid background.
Hemoglobin istanbul: substitution of glutamine for histidine in a proximal histidine (F8(92)β)
Authors: M. Aksoy, S. Erdem, G. D. Efremov, J. B. Wilson, T. H. J. Huisman, W. A. Schroeder, J. R. Shelton, J. B. Shelton, O. N. Ulitin, A. Müftüoglu
Journal: Journal of Clinical Investigation (1972)

A presumably spontaneous mutation has resulted in the formation of Hemoglobin (Hb) Istanbul in which glutamine is substituted for histidine in the proximal position of the beta-chain (F8(92)). The anemia and other physiological effects that occur in the presence of Hb Istanbul were much ameliorated by splenectomy. Hb Istanbul is a relatively unstable molecule which produces a rather moderate case of "unstable hemoglobin hemolytic anemia."In the determination of structure, a method of preferential cleavage of an aspartyl-proline bond at residues 99-100 of the beta-chain was used.
Delayed Hemolytic Transfusion Reaction Presenting as Sickle-Cell Crisis
Authors: W. JOHN DIAMOND
Journal: Annals of Internal Medicine (1980)

Eighteen patients with sickle-cell disease underwent partial exchange transfusion. Three developed delayed hemolytic reactions, with selective disappearance of transfused cells. All reactions occurred within 6 days of transfusion, and patients presented with the clinical features of painful crises. The two most severe reactions were associated with antibodies to Jka. These patients developed fever, arthritis, and a clinical course suggesting serum sickness. In both patients, other alloantibodies had previously been seen. A fourth patient developed multiple alloantibodies, accelerated destruction of transfused cells, but milder illness. Such reactions may be commoner than is appreciated and should be suspected when patients have recurrent or severe sickle crises after transfusion. Blood that is nonimmunogenic in antigen systems frequently associated with delayed hemolytic reactions (Rh, Kell, Duffy, and Kidd) is preferred for sickle-cell patients who lack these antigens, especially if these patients have previously demonstrated capability to form erythrocyte alloantibodies.
Evaluation of the Accuracy of Gadolinium-Enhanced Cardiovascular Magnetic Resonance in the Diagnosis of Cardiac Sarcoidosis
Authors: Jan-Peter Smedema, Gabriel Snoep, Marinus P.G. van Kroonenburgh, Robert-Jan van Geuns, Willem R.M. Dassen, Anton P.M. Gorgels, Harry J.G.M. Crijns
Journal: Journal of the American College of Cardiology (2005)
Galectin-3, a Novel Binding Partner of β-Catenin
Authors: Tatsuo Shimura, Yukinori Takenaka, Souichi Tsutsumi, Victor Hogan, Akira Kikuchi, Avraham Raz
Journal: Cancer Research (2004)

Abstract Galectin-3 (gal-3), a pleiotrophic protein, is an important regulator of tumor metastasis, which like β-catenin shuttles between the nucleus and the cytosol in a phosphorylation-dependent manner. We report herein that β-catenin stimulation of cyclin D1 and c-myc expression is gal-3 dependent. Gal-3 binds to β-catenin/Tcf complex, colocalizes with β-catenin in the nucleus, and induces the transcriptional activity of Tcf-4 as determined by the TOP/FOPFLASH reporter system. We have identified the β-catenin–gal-3–binding sequences, which are in the NH2 and COOH termini of the proteins encompassing amino acid residues 1 to 131 and 143 to 250, respectively. These data indicate that gal-3 is a novel binding partner for β-catenin involved in the regulation of Wnt/β-catenin signaling pathway.
Plasma Levels of Metalloproteinases-3 and -9 as Markers of Successful Abdominal Aortic Aneurysm Exclusion After Endovascular Graft Treatment
Authors: Giuseppe Sangiorgi, Rita D’Averio, Alessandro Mauriello, Monya Bondio, Marina Pontillo, Serenella Castelvecchio, Santi Trimarchi, Valerio Tolva, Giovanni Nano, Vincenzo Rampoldi, Luigi Giusto Spagnoli, Luigi Inglese
Journal: Circulation (2001)

Structural alterations of aortic wall resulting from degradation of matrix proteins by matrix metalloproteinases (MMPs) characterize abdominal aortic aneurysms (AAAs). No studies have compared circulating levels of MMPs after endovascular graft (EVG) exclusion in comparison with open surgical repair (OSR) in patients affected by AAA.An abdominal angiography and CT scan were performed in all patients at the time of enrollment. A spiral CT scan was performed at 6 months to detect presence of endoleaks. MMP-3 and MMP-9 levels were measured before EVG (n=30) and OSR (n=15) treatments and at 1, 3, and 6 months of follow-up by a sandwich ELISA technique. Healthy volunteers (n=10) were used as control subjects. Immunohistochemical staining for MMP-9 and MMP-3 was performed on tissue samples from surgical cases. Both MMP-9 and MMP-3 mean basal levels were significantly higher in patients affected by AAA than in control subjects (32.3+/-20.7 ng/mL for EVG and 28+/-9.9 ng/mL for OSR versus 8.9+/-2.5 ng/mL, 2P<0.05; 18.3+/-9.7 ng/mL and 26.7+/-10.8 ng/mL versus 8.2+/-5.3 ng/mL, 2P<0.001). In the OSR group, both MMP-9 and MMP-3 mean levels decreased after surgery (28+/-9.9 ng/mL at basal versus 14.7+/-6.6 ng/mL at 6 months, 2P<0.001; 26.7+/-10.8 versus 12+/-5.3 ng/mL; 2P<0.001). In the EVG group, a statistically significant difference at 6-month follow-up in MMP-9 and MMP-3 mean plasma values was detected in patients who had endoleakage in comparison with patients without endoleakage (44.3+/-20.7 versus 14.6+/-7.0 ng/mL, 2P<0.005; 25+/-11.5 versus 10.3+/-5.4 ng/mL, 2P<0.005).After EVG exclusion, MMP-9 and MMP-3 levels decreased to a level similar to that of patients undergoing OSR. In addition, a lack of decrease in MMP levels after EVG exclusion may help in identifying patients who will have endoleakage and consequent aneurysm expansion caused by continuous sac pressurization during follow-up.
CELLULAR AND VASCULAR COMPONENTS OF THE ALLOGRAFT REACTION
Authors: Peter B. Lambert, Howard A. Frank
Journal: The Journal of Experimental Medicine (1970)

In order to gain added insight into the mechanisms of allograft destruction, skin grafts were returned to their original donors after remaining as allografts long enough to induce immunity in the intermediate host but not long enough to cause destruction of the graft. Upon their return to unmodified donors, such grafts became revascularized and remained viable. An intense cellular infiltration was incited within the graft and its draining lymph node by the interaction between immunologically competent cells, some antigenically activated, that were transferred from the intermediate host with the graft, and those of the final host, the original donor. This immune interaction excited a nonspecific granulocytic and histiocytic response, which led to the destruction of the adjacent epithelium already re-accepted within its native habitat. This mechanism of epithelial destruction required vascular connection to permit the cellular infiltration, and was unlikely to have primarily involved circulating antibody. When similar grafts were returned to donors that had been sensitized to the intermediate host, vascularization and reacceptance of the graft did not occur. No cellular infiltration took place in the graft and no lymph node response was evoked. The returned grafts were cast off as full-thickness sloughs. Here the mechanism of graft rejection was apparently an interaction between the preformed antibody of the specifically sensitized host and the allogeneic cells transferred from the intermediate host; this interaction prevented the vascularization of the graft, even though the endothelia involved were autologous. In unmodified allografts, both the character and the variability of the histologic patterns can be accounted for by the superimposition, in differing rates and degrees, of humoral vascular effects upon cellular events already in progress.
Human hepatocyte growth factor in bile: An indicator of posthepatectomy liver function in patients with biliary tract carcinoma
Authors: E Takeuchi, Y Nimura, M Nagino, Y Kurumiya, A Maeda, J Kamiya, S Kondo, M Kanai, M Miyachi, K Uesaka, S Yoshida
Journal: Hepatology (1997)

We measured the concentration of hepatocyte growth factor (HGF) in bile obtained from patients after hepatectomy. The HGF concentrations in the bile samples were quantified using an enzyme-linked immunosorbent assay (ELISA). By immunoblotting, using a monoclonal antibody raised against the HGF α-subunit, the bile HGF, which was purified on a Heparin-Sepharose column, showed a band of the same size as the recombinant HGF α-subunit (69 kd). Bile samples were obtained from 24 patients with biliary tract disease before and after hepatectomy by means of biliary drainage. Before surgery, the bile HGF concentrations were minimal (0.8 ± 0.1 ng/mL); however, after hepatectomy on postoperative day 1 in patients without posthepatectomy liver failure (20 of 24), they increased severalfold (4.1 ± 0.4 ng/mL, P &lt; .05). The patients with posthepatectomy liver failure (4 of 24) showed no significant increase in bile HGF after hepatectomy (less than 2 ng/mL on postoperative day 1). The volume of the remnant liver correlated positively with the bile HGF concentration. The bile HGF concentration on postoperative day 1 exhibited a significant negative correlation with the maximum concentration of serum total bilirubin after hepatectomy. The concentration of bile HGF was generally higher than that in serum (2.1-fold). Thus, the bile HGF concentration after hepatectomy may be useful for the early assessment of posthepatectomy liver function.
Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels.
Authors: J C Cohen, Z Wang, S M Grundy, M R Stoesz, R Guerra
Journal: Journal of Clinical Investigation (1994)

Genetic factors have been shown to play an important role in determining interindividual variation in plasma HDL-C levels, but the specific genetic determinants of HDL cholesterol (HDL-C) levels have not been elucidated. In this study, the effects of variation in the genomic regions encoding hepatic lipase, apolipoprotein AI/CIII/AIV, and the cholesteryl ester transfer protein on plasma HDL-C levels were examined in 73 normotriglyceridemic, Caucasian nuclear families. Genetic factors accounted for 56.5 +/- 13% of the interindividual variation in plasma HDL-C levels. For each candidate gene, adjusted plasma HDL-C levels of sibling pairs who shared zero, one, or two parental alleles identical-by-descent were compared using sibling-pair linkage analysis. Allelic variation in the genes encoding hepatic lipase and apolipoprotein AI/CIII/AIV accounted for 25 and 22%, respectively, of the total interindividual variation in plasma HDL-C levels. In contrast, none of the variation in plasma HDL-C levels could be accounted for by allelic variation in the cholesteryl ester transfer protein. These findings indicate that a major fraction of the genetically determined variation in plasma HDL-C levels is conferred by allelic variation at the hepatic lipase and the apolipoprotein AI/CIII/AIV gene loci.
Antibody-dependent eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: damage by purieid eosinophils.
Authors: A E Butterworth, J R David, D Franks, A A Mahmoud, P H David, R F Sturrock, V Houba
Journal: The Journal of Experimental Medicine (1977)

After earlier observations that antibody-dependent, cell-mediated damage to 51Cr-labeled schistosomula can be ablated by pretreatment of a mixed preparation of human peripheral blood leukocytes with an anti-eosinophil serum and complement, we investigated the cytotoxic effects of eosinophil-enriched cell preparations. Preparations containing up to 98.5% eosinophils and devoid of neutrophils were effective in mediating antibody-dependent damage to schistosomula. Preparations enriched in mononuclear cells or in neutrophils, and devoid of eosinophils, were inactive. Eosinophils from some patients with eosinophilia induced by schistosomiasis were less active on a cell-to-cell basis than cells from normal individuals. The possibility that such cells were initially blocked by immune complexes was considered, and it was found that reasonable cytotoxicity by purified eosinophils from patients with eosinophilia could be generated by overnight cultures. A possible requirement for cooperation between eosinophils and other cell types was also studied. Lymphocytes, neutrophils and monocytes failed to enhance eosinophil-mediated cytotoxicity. These results provide further evidence that the eosinophil is the only cell in man responsible for antibody-dependent, complement-independent damage to schistosomula in vitro. Eosinophils from individuals, however, differ in their cytotoxic potential by a mechanism yet to be elucidated. The possible relationship of these findings to immunity in vivo is discussed.
Effectiveness of sequential automatic-manual home respiratory polygraphy scoring
Authors: Juan F. Masa, Jaime Corral, Ricardo Pereira, Joaquin Duran-Cantolla, Marta Cabello, Luis Hernández-Blasco, Carmen Monasterio, Alberto Alonso-Fernandez, Eusebi Chiner, Francisco-José Vázquez-Polo, Jose M. Montserrat
Journal: European Respiratory Journal (2012)

Automatic home respiratory polygraphy (HRP) scoring functions can potentially confirm the diagnosis of sleep apnoea-hypopnoea syndrome (SAHS) (obviating technician scoring) in a substantial number of patients. The result would have important management and cost implications. The aim of this study was to determine the diagnostic cost-effectiveness of a sequential HRP scoring protocol (automatic and then manual for residual cases) compared with manual HRP scoring, and with in-hospital polysomnography. We included suspected SAHS patients in a multicentre study and assigned them to home and hospital protocols at random. We constructed receiver operating characteristic (ROC) curves for manual and automatic scoring. Diagnostic agreement for several cut-off points was explored and costs for two equally effective alternatives were calculated. Of 366 randomised patients, 348 completed the protocol. Manual scoring produced better ROC curves than automatic scoring. There was no sensitive automatic or subsequent manual HRP apnoea–hypopnoea index (AHI) cut-off point. The specific cut-off points for automatic and subsequent manual HRP scorings (AHI &gt;25 and &gt;20, respectively) had a specificity of 93% for automatic and 94% for manual scorings. The costs of manual protocol were 9% higher than sequential HRP protocol; these were 69% and 64%, respectively, of the cost of the polysomnography. A sequential HRP scoring protocol is a cost-effective alternative to polysomnography, although with limited cost savings compared to HRP manual scoring.