tbuckley/cabot-search huggingface dataset:
Impaired left ventricular function in chronic aortic valve disease: survival and function after replacement by Björk-Shiley prosthesis.
Authors: F Schwarz, W Flameng, F Langebartels, M Sesto, P Walter, M Schlepper
Journal: Circulation (1979)

Postoperative survival and left ventricular function were studied in 128 patients who underwent isolated aortic valve replacement by the Björk-Shiley valve between 1973 and 1977. The average follow-up was 2.1 years. Patients with associated coronary artery disease or mitral valve disease were excluded. Preoperative ejection fraction ranged from 15-84%. Forty-two patients were restudied by cardiac catheterization 9.1 +/- 1.1 months (mean +/- SEM) after valve replacement. The hospital mortality was 11%. Preoperative type of valve lesion, functional class, cardiothoracic ratio, and ejection fraction (EF) had no significant effect on postoperative survival up to 4 years. After operation, left ventricular mass (LVMI) and peak systolic wall stress (PSWS) fell significantly, while EF and mean normalized systolic ejection rate (MNSER) increased in aortic stenosis and in aortic insufficiency. Neither in aortic stenosis nor in aortic insufficiency was there a significant relation between preoperative ejection fraction and postoperative LVMI, EF, MNSER and PSWS. We attributed this to a marked improvement of left ventricular function in patients with preoperative impaired ventricular function. Six patients with paravalvular leak to restudy has a significantly lower EF and MNSER, and a higher PSWS than patients without leak. Patients without leak had normal EF, MNSER and PSWS when compared with 10 normal persons, but LVMI remained moderately elevated. Postoperative transprosthetic gradient was 11.9 mm Hg (range 0-64 mm Hg). We conclude that impaired cardiac function is completely restored after aortic valve replacement by Björk-Shiley valve, if valve function is good. Patients with impaired cardiac function preoperatively did not have a poorer prognosis after operation than patients with normal function.
Toll-like receptor 4 induced Fc R expression potentiates early onset of joint inflammation and cartilage destruction during immune complex arthritis: Toll-like receptor 4 largely regulates Fc R expression by interleukin 10
Authors: P L E M van Lent, A B Blom, L Grevers, A Sloetjes, W B van den Berg
Journal: Annals of the Rheumatic Diseases (2006)

To study the role of Toll-like receptor (TLR)2 and 4 in the onset of joint inflammation and cartilage destruction during immune complex-mediated arthritis (ICA), and its relationship with FcgammaR expression.ICA was induced in knee joints of TLR2-/- and TLR4-/- mice and their wild-type controls. Joint inflammation and cartilage destruction were measured in the knee joint using histology. mRNA levels were determined in synovial specimens and macrophages using quantitative polymerase chain reaction and cytokine protein levels in synovial washouts using Bioplex.Joint inflammation and cartilage destruction were not different in arthritic TLR2-/- and wild-type mice. By contrast, at day 1 after ICA induction, joint swelling and proteoglycan depletion in knee joints of TLR4-/- mice were considerably lower (inflammation 68-79% and proteoglycan depletion 27-76%) when compared with wild-type controls. Cytokine production at this time point was markedly reduced in TLR4-/- mice (interleukin (IL)1, IL6, macrophage inflammatory chemokine (MIP)-1alpha and keratinocyte-derived chemokine 49%, 72%, 68% and 84%, respectively). In arthritic synovia of TLR4-/- mice, and also after injection of the antigen poly-l-lysine (PLL) lysozyme alone, mRNA levels of FcgammaR, and the FcgammaR regulating cytokine IL10 were considerably lower. Stimulation of peritoneal macrophages with PLL lysozyme up regulated mRNA levels of FcgammaR and IL10, whereas neutralisation by anti-IL10 antibodies largely blocked FcgammaR up regulation. At day 4, joint inflammation and cartilage destruction were comparable in TLR4-/- mice and wild-type controls.TLR4 regulates early onset of joint inflammation and cartilage destruction during ICA arthritis by up regulation of FcgammaR expression and enhanced cytokine production. TLR4-mediated up regulation of FcgammaR is largely mediated by IL10.
Does metacognition necessarily involve metarepresentation?
Authors: Joëlle Proust
Journal: Behavioral and Brain Sciences (2003)

Against the view that metacognition is a capacity that parallels theory of mind, it is argued that metacognition need involve neither metarepresentation nor semantic forms of reflexivity, but only process-reflexivity, through which a task-specific system monitors its own internal feedback by using quantitative cues. Metacognitive activities, however, may be redescribed in metarepresentational, mentalistic terms in species endowed with a theory of mind.
Onset of Abnormal Blood and Lymphatic Vessel Function and Interstitial Hypertension in Early Stages of Carcinogenesis
Authors: Jeroen Hagendoorn, Ricky Tong, Dai Fukumura, Qingcong Lin, Jennifer Lobo, Timothy P. Padera, Lei Xu, Raju Kucherlapati, Rakesh K. Jain
Journal: Cancer Research (2006)

Abstract Recent improvements in diagnostic methods have opened avenues for detection and treatment of (pre)malignant lesions at early stages. However, due to the lack of spontaneous tumor models that both mimic human carcinogenesis and allow direct optical imaging of the vasculature, little is known about the function of blood and lymphatic vessels during the early stages of cancer development. Here, we used a spontaneous carcinogenesis model in the skin of DNA polymerase η–deficient mice and found that interstitial fluid pressure was already elevated in the hyperplastic/dysplastic stage. This was accompanied by angiogenic blood vasculature that exhibited altered permeability, vessel compression, and decreased α-smooth muscle actin–positive perivascular cell coverage. In addition, the lymphatic vessels in hyperplastic/dysplastic lesions were partly compressed and nonfunctional. These novel insights may aid early detection and treatment strategies for cancer. (Cancer Res 2006; 66(7): 3360-4)
Attenuated acute liver injury in mice by naked hepatocyte growth factor gene transfer into skeletal muscle with electroporation
Authors: F Xue
Journal: Gut (2002)

Hepatocyte growth factor (HGF) plays an essential role in hepatic development and regeneration, and shows proliferative and antiapoptotic activity in hepatocytes.To establish an effective new method for HGF gene transfer in vivo and to investigate its effects in acute experimental liver injury.Eight week old female mice were used.Rat HGF gene in a modified pKSCX plasmid was transferred to the tibialis anterior muscle by electroporation using a pulse generator. Four days later, plasma HGF concentrations were determined by enzyme linked immunosorbent assay every two days for three weeks. To confirm the efficacy of electroporation, a plasmid bearing green fluorescence protein (GFP) was transferred similarly. Four days after electroporation, carbon tetrachloride (CCl(4)) was administered to mice to induce acute liver injury. Plasma alanine aminotransferase (ALT) activity was measured. Hepatic apoptosis was assessed by Hoechst 33258 staining and the TUNEL method.Fluorescence microscopy showed strong green fluorescence where the GFP gene had been transferred into muscle. In mice given the HGF gene, HGF in plasma was increased up to fourfold from pretreatment amounts, peaking 6-9 days after electroporation and quickly decreasing within three weeks. Compared with the group without HGF transfer, the percentage of apoptotic hepatocytes after CCl(4) intoxication was significantly lower, as was ALT activity. In addition, ALT activity normalised more rapidly in the HGF gene transfer group.Naked DNA injection and transfer by electroporation efficiently brings about HGF expression in vivo, which can attenuate acute liver injury.
Tumor Hypoxia Does Not Drive Differentiation of Tumor-Associated Macrophages but Rather Fine-Tunes the M2-like Macrophage Population
Authors: Damya Laoui, Eva Van Overmeire, Giusy Di Conza, Chiara Aldeni, Jiri Keirsse, Yannick Morias, Kiavash Movahedi, Isabelle Houbracken, Elio Schouppe, Yvon Elkrim, Oussama Karroum, Bénédicte Jordan, Peter Carmeliet, Conny Gysemans, Patrick De Baetselier, Massimiliano Mazzone, Jo A. Van Ginderachter
Journal: Cancer Research (2013)

Tumor-associated macrophages (TAM) are exposed to multiple microenvironmental cues in tumors, which collaborate to endow these cells with protumoral activities. Hypoxia, caused by an imbalance in oxygen supply and demand because of a poorly organized vasculature, is often a prominent feature in solid tumors. However, to what extent tumor hypoxia regulates the TAM phenotype in vivo is unknown. Here, we show that the myeloid infiltrate in mouse lung carcinoma tumors encompasses two morphologically distinct CD11b(hi)F4/80(hi)Ly6C(lo) TAM subsets, designated as MHC-II(lo) and MHC-II(hi) TAM, both of which were derived from tumor-infiltrating Ly6C(hi) monocytes. MHC-II(lo) TAM express higher levels of prototypical M2 markers and reside in more hypoxic regions. Consequently, MHC-II(lo) TAM contain higher mRNA levels for hypoxia-regulated genes than their MHC-II(hi) counterparts. To assess the in vivo role of hypoxia on these TAM features, cancer cells were inoculated in prolyl hydroxylase domain 2 (PHD2)-haplodeficient mice, resulting in better-oxygenated tumors. Interestingly, reduced tumor hypoxia did not alter the relative abundance of TAM subsets nor their M2 marker expression, but specifically lowered hypoxia-sensitive gene expression and angiogenic activity in the MHC-II(lo) TAM subset. The same observation in PHD2(+/+) → PHD2(+/-) bone marrow chimeras also suggests organization of a better-oxygenized microenvironment. Together, our results show that hypoxia is not a major driver of TAM subset differentiation, but rather specifically fine-tunes the phenotype of M2-like MHC-II(lo) TAM.
Low Likelihood of Intracranial Hemorrhage in Patients With Cirrhosis and Altered Mental Status
Authors: Lucas M Donovan, Whitney L Kress, Luke C Strnad, Ammar Sarwar, Vilas Patwardhan, Gail Piatkowski, Elliot B Tapper, Nezam H Afdhal
Journal: Clinical Gastroenterology and Hepatology (2014)
BCR-ABL truncation due to premature translation termination as a mechanism of resistance to kinase inhibitors
Authors: C. Yeh, W. Ma, H. Kantarjian, Z. J. Zhang, J. Cortes, M. Albitar
Journal: Journal of Clinical Oncology (2009)

7028 Background: The major mechanism underlying imatinib resistance in patients with chronic myeloid leukemia (CML) is clonal expansion of leukemic cells with point mutations in the BCR-ABL tyrosine kinase. We describe three novel ABL premature termination mutations leading to BCR-ABL truncation in leukemia patients with multidrug (imatinib/nilotinib/dasatinib) resistance. Methods: Peripheral blood or bone marrow samples from drug-resistant CML patients were collected. Total nucleic acids were purified and subjected to two rounds of PCR analysis, with the first PCR designed to eliminate amplification of the wild-type, non-translocated ABL gene. Bi-directional sequencing was then performed. HL60 cells (a Ph-negative myeloid leukemia cell line) and peripheral blood of healthy subjects were used as negative controls; a human CML cell line (K562) was used as a positive control. Results: We identified an exon 7 deletion in three CML patients, a 4-nt insertion (908insCAGG) near the exon 5/6 junction in one CML case, and an exon 6 point mutation (997C&gt;T) in one patient with acute lymphoblastic leukemia (ALL). These mutations all create premature stop codons and cause termination at residues 381, 315, and 333, respectively, leading to truncated proteins with only the first quarter of the kinase domain (P-loop) or lacking the C-terminus of ABL including the A-loop. Conclusions: These novel mutations, and the previously documented 35-nt insertion in exon 8, may constitute a new class of mutations that 1) cause truncation of the BCR-ABL kinase; (2) abolish the regulatory element in the ABL kinase domain and the downstream C-terminal region; and (3) confer significant drug resistance. [Table: see text]
Comparison of Three Protocols for Tight Glycemic Control in Cardiac Surgery Patients
Authors: Jan Blaha, Petr Kopecky, Michal Matias, Roman Hovorka, Jan Kunstyr, Tomas Kotulak, Michal Lips, David Rubes, Martin Stritesky, Jaroslav Lindner, Michal Semrad, Martin Haluzik
Journal: Diabetes Care (2009)

OBJECTIVE We performed a randomized trial to compare three insulin-titration protocols for tight glycemic control (TGC) in a surgical intensive care unit: an absolute glucose (Matias) protocol, a relative glucose change (Bath) protocol, and an enhanced model predictive control (eMPC) algorithm. RESEARCH DESIGN AND METHODS A total of 120 consecutive patients after cardiac surgery were randomly assigned to the three protocols with a target glycemia range from 4.4 to 6.1 mmol/l. Intravenous insulin was administered continuously or in combination with insulin boluses (Matias protocol). Blood glucose was measured in 1- to 4-h intervals as requested by the protocols. RESULTS The eMPC algorithm gave the best performance as assessed by time to target (8.8 ± 2.2 vs. 10.9 ± 1.0 vs. 12.3 ± 1.9 h; eMPC vs. Matias vs. Bath, respectively; P &amp;lt; 0.05), average blood glucose after reaching the target (5.2 ± 0.1 vs. 6.2 ± 0.1 vs. 5.8 ± 0.1 mmol/l; P &amp;lt; 0.01), time in target (62.8 ± 4.4 vs. 48.4 ± 3.28 vs. 55.5 ± 3.2%; P &amp;lt; 0.05), time in hyperglycemia &amp;gt;8.3 mmol/l (1.3 ± 1.2 vs. 12.8 ± 2.2 vs. 6.5 ± 2.0%; P &amp;lt; 0.05), and sampling interval (2.3 ± 0.1 vs. 2.1 ± 0.1 vs. 1.8 ± 0.1 h; P &amp;lt; 0.05). However, time in hypoglycemia risk range (2.9–4.3 mmol/l) in the eMPC group was the longest (22.2 ± 1.9 vs. 10.9 ± 1.5 vs. 13.1 ± 1.6; P &amp;lt; 0.05). No severe hypoglycemic episode (&amp;lt;2.3 mmol/l) occurred in the eMPC group compared with one in the Matias group and two in the Bath group. CONCLUSIONS The eMPC algorithm provided the best TGC without increasing the risk of severe hypoglycemia while requiring the fewest glucose measurements. Overall, all protocols were safe and effective in the maintenance of TGC in cardiac surgery patients.
Antiretroviral Pre-exposure Prophylaxis Prevents Vaginal Transmission of HIV-1 in Humanized BLT Mice
Authors: Paul W Denton, Jacob D Estes, Zhifeng Sun, Florence A Othieno, Bangdong L Wei, Anja K Wege, Daniel A Powell, Deborah Payne, Ashley T Haase, J. Victor Garcia
Journal: PLoS Medicine (2008)

Background Worldwide, vaginal transmission now accounts for more than half of newly acquired HIV-1 infections. Despite the urgency to develop and implement novel approaches capable of preventing HIV transmission, this process has been hindered by the lack of adequate small animal models for preclinical efficacy and safety testing. Given the importance of this route of transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1 infection. Methods and Findings We show that the female reproductive tract of humanized bone marrow–liver–thymus (BLT) mice is reconstituted with human CD4+ T and other relevant human cells, rendering these humanized mice susceptible to intravaginal infection by HIV-1. Effects of HIV-1 infection include CD4+ T cell depletion in gut-associated lymphoid tissue (GALT) that closely mimics what is observed in HIV-1–infected humans. We also show that pre-exposure prophylaxis with antiretroviral drugs is a highly effective method for preventing vaginal HIV-1 transmission. Whereas 88% (7/8) of BLT mice inoculated vaginally with HIV-1 became infected, none of the animals (0/5) given pre-exposure prophylaxis of emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) showed evidence of infection (Chi square = 7.5, df = 1, p = 0.006). Conclusions The fact that humanized BLT mice are susceptible to intravaginal infection makes this system an excellent candidate for preclinical evaluation of both microbicides and pre-exposure prophylactic regimens. The utility of humanized mice to study intravaginal HIV-1 transmission is particularly highlighted by the demonstration that pre-exposure prophylaxis can prevent intravaginal HIV-1 transmission in the BLT mouse model.
Zinc Finger Protein, <i>Hzf</i>, Is Required for Megakaryocyte Development and Hemostasis
Authors: Yuki Kimura, Adam Hart, Masanori Hirashima, Chen Wang, Doug Holmyard, Jackie Pittman, Xin-Li Pang, Carl W. Jackson, Alan Bernstein
Journal: The Journal of Experimental Medicine (2002)

Using an expression gene trapping strategy, we recently identified a novel gene, hematopoietic zinc finger (Hzf), which encodes a protein containing three C2H2-type zinc fingers that is predominantly expressed in megakaryocytes. Here, we have examined the in vivo function of Hzf by gene targeting and demonstrated that Hzf is essential for megakaryopoiesis and hemostasis in vivo. Hzf-deficient mice exhibited a pronounced tendency to rebleed and had reduced α-granule substances in both megakaryocytes and platelets. These mice also had large, faintly stained platelets, whereas the numbers of both megakaryocytes and platelets were normal. These results indicate that Hzf plays important roles in regulating the synthesis of α-granule substances and/or their packing into α-granules during the process of megakaryopoiesis.
HSulf-1 Modulates FGF2- and Hypoxia-Mediated Migration and Invasion of Breast Cancer Cells
Authors: Ashwani Khurana, Peng Liu, Pasquale Mellone, Laura Lorenzon, Bruno Vincenzi, Kaustubh Datta, Bo Yang, Robert J. Linhardt, Wilma Lingle, Jeremy Chien, Alfonso Baldi, Viji Shridhar
Journal: Cancer Research (2011)

HSulf-1 modulates the sulfation states of heparan sulfate proteoglycans critical for heparin binding growth factor signaling. In the present study, we show that HSulf-1 is transcriptionally deregulated under hypoxia in breast cancer cell lines. Knockdown of HIF-1α rescued HSulf-1 downregulation imposed by hypoxia, both at the RNA and protein levels. Chromatin immunoprecipitation with HIF-1α and HIF-2α antibodies confirmed recruitment of HIF-α proteins to the two functional hypoxia-responsive elements on the native HSulf-1 promoter. HSulf-1 depletion in breast cancer cells resulted in an increased and sustained bFGF2 (basic fibroblast growth factor) signaling and promoted cell migration and invasion under hypoxic conditions. In addition, FGFR2 (fibroblast growth factor receptor 2) depletion in HSulf-1-silenced breast cancer cells attenuated hypoxia-mediated cell invasion. Immunohistochemical analysis of 53 invasive ductal carcinomas and their autologous metastatic lesions revealed an inverse correlation for the expression of HSulf-1 to CAIX in both the primary tumors (P ≥ 0.0198) and metastatic lesions (P ≥ 0.0067), respectively, by χ(2) test. Finally, HSulf-1 expression levels in breast tumors by RNA in situ hybridization showed that high HSulf-1 expression is associated with increased disease-free and overall survival (P ≥ 0.03 and P ≥ 0.0001, respectively). Collectively, these results reveal an important link between loss of HSulf-1 under hypoxic microenvironment and increased growth factor signaling, cell migration, and invasion.
Delivering the diabetes education and self management for ongoing and newly diagnosed (DESMOND) programme for people with newly diagnosed type 2 diabetes: cost effectiveness analysis
Authors: M. Gillett, H. M. Dallosso, S. Dixon, A. Brennan, M. E. Carey, M. J. Campbell, S. Heller, K. Khunti, T. C. Skinner, M. J. Davies
Journal: BMJ (2010)

<b>Objectives</b> To assess the long term clinical and cost effectiveness of the diabetes education and self management for ongoing and newly diagnosed (DESMOND) intervention compared with usual care in people with newly diagnosed type 2 diabetes. <b>Design</b> We undertook a cost-utility analysis that used data from a 12 month, multicentre, cluster randomised controlled trial and, using the Sheffield type 2 diabetes model, modelled long term outcomes in terms of use of therapies, incidence of complications, mortality, and associated effect on costs and health related quality of life. A further cost-utility analysis was also conducted using current "real world" costs of delivering the intervention estimated for a hypothetical primary care trust. <b>Setting</b> Primary care trusts in the United Kingdom. <b>Participants</b> Patients with newly diagnosed type 2 diabetes. <b>Intervention</b> A six hour structured group education programme delivered in the community by two professional healthcare educators. <b>Main outcome measures</b> Incremental costs and quality adjusted life years (QALYs) gained. <b>Results</b> On the basis of the data in the trial, the estimated mean incremental lifetime cost per person receiving the DESMOND intervention is £209 (95% confidence interval −£704 to £1137; €251, −€844 to €1363; $326, −$1098 to $1773), the incremental gain in QALYs per person is 0.0392 (−0.0813 to 0.1786), and the mean incremental cost per QALY is £5387. Using "real world" intervention costs, the lifetime incremental cost of the DESMOND intervention is £82 (−£831 to £1010) and the mean incremental cost per QALY gained is £2092. A probabilistic sensitivity analysis indicated that the likelihood that the DESMOND programme is cost effective at a threshold of £20 000 per QALY is 66% using trial based intervention costs and 70% using "real world" costs. Results from a one way sensitivity analysis suggest that the DESMOND intervention is cost effective even under more modest assumptions that include the effects of the intervention being lost after one year. <b>Conclusion</b> Our results suggest that the DESMOND intervention is likely to be cost effective compared with usual care, especially with respect to the real world cost of the intervention to primary care trusts, with reductions in weight and smoking being the main benefits delivered.
EUTHYROID SICK SYNDROME AND FREE THYROXINE ASSAY
Authors: R.P. Ekins, T. Jackson, P. Edwards, C. Salter, I. Ogier, Rhys John, Robert Henley, Jens Faber, Carsten Kirkegaard, Kaj Siersbaek-Nielsen, Thorkild Friis
Journal: The Lancet (1983)
Changes in Cognitive Functioning Following Treatment of Late-Life Depression
Authors: Meryl A. Butters, James T. Becker, Robert D. Nebes, Michelle D. Zmuda, Benoit H. Mulsant, Bruce G. Pollock, Charles F. Reynolds
Journal: American Journal of Psychiatry (2000)

Knowledge of the relationship between various clinical characteristics and cognitive functioning is advancing, but little is known about the cognitive response to treatment for geriatric depression. The purpose of this study was to examine the cognitive response to treatment for patients with late-life depression.Subjects included 45 nondemented, elderly depressed patients who achieved remission after 12 weeks of antidepressant treatment and 20 elderly comparison subjects. All subjects were administered a battery of clinical measures, including cognitive screening instruments, before and after treatment.As a group, the elderly depressed patients showed a small improvement in overall cognitive functioning after treatment. Among depressed patients with concomitant cognitive impairment at baseline, performance on the Mattis Dementia Rating Scale domains of conceptualization and initiation/perseveration improved significantly relative to those of depressed patients with normal cognition. Despite the improvement following treatment, the overall level of cognitive functioning in the elderly depressed patients with cognitive impairment at baseline remained mildly impaired, especially in the memory and initiation/perseveration domains.Elderly depressed patients with cognitive impairment may experience improvement in specific domains following antidepressant treatment but may not necessarily reach normal levels of performance, particularly in memory and executive functions. This subgroup of late-life depression patients is likely at high risk of developing progressive dementia.