tbuckley/cabot-search huggingface dataset:
The Human Immunodeficiency Virus Type 1 (HIV-1) Vpu Protein Interferes with an Early Step in the Biosynthesis of Major Histocompatibility Complex (MHC) Class I Molecules
Authors: Thomas Kerkau, Igor Bacik, Jack R. Bennink, Jonathan W. Yewdell, Thomas Hünig, Anneliese Schimpl, Ulrich Schubert
Journal: The Journal of Experimental Medicine (1997)

The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a small integral membrane phosphoprotein with two established functions: degradation of the viral coreceptor CD4 in the endoplasmic reticulum (ER) and augmentation of virus particle release from the plasma membrane of HIV-1–infected cells. We show here that Vpu is also largely responsible for the previously observed decrease in the expression of major histocompatibility complex (MHC) class I molecules on the surface of HIV-1–infected cells. Cells infected with HIV-1 isolates that fail to express Vpu, or that express genetically modified forms of Vpu that no longer induce CD4 degradation, exhibit little downregulation of MHC class I molecules. The effect of Vpu on class I biogenesis was analyzed in more detail using a Vpu-expressing recombinant vaccinia virus (VV). VV-expressed Vpu induces the rapid loss of newly synthesized endogenous or VV-expressed class I heavy chains in the ER, detectable either biochemically or by reduced cell surface expression. This effect is of similar rapidity and magnitude as the VV-expressed Vpu-induced degradation of CD4. Vpu had no discernible effects on cell surface expression of VV-expressed mouse CD54, demonstrating the selectivity of its effects on CD4 and class I heavy chains. VVexpressed Vpu does not detectably affect class I molecules that have been exported from the ER. The detrimental effects of Vpu on class I molecules could be distinguished from those caused by VV-expressed herpes virus protein ICP47, which acts by decreasing the supply of cytosolic peptides to class I molecules, indicating that Vpu functions in a distinct manner from ICP47. Based on these findings, we propose that Vpu-induced downregulation of class I molecules may be an important factor in the evolutionary selection of the HIV-1–specific vpu gene by contributing to the inability of CD8+ T cells to eradicate HIV-1 from infected individuals.
Medical Education In China
Authors: R. Edward Dodge
Journal: JAMA (1972)

<h3>To the Editor.—</h3> I have just finished reading the articles by Dimond in the Dec 6, 1971 issue ofThe Journal, and think they are of extraordinary interest. While every aspect of this glimpse into Chinese medicine was fascinating, I would like to comment particularly on the present medical curriculum in China, as outlined by Dimond. Having worked and taught in Ethiopia for two years in the field of public health, there is no doubt in my mind that the type of medical curriculum being used in China is far more appropriate to the needs of the developing world than the usual type of medical curriculum found in Western countries such as our own. This is true with regard to the shortened length of the curriculum, the easing of academic prerequisites, the emphasis on practical experience in both clinical and preventive medicine, and the apparent deemphasis on specialization. Unfortunately, most countries
Very late activation antigen 4-vascular cell adhesion molecule 1 interaction is involved in the formation of erythroblastic islands.
Authors: Y Sadahira, T Yoshino, Y Monobe
Journal: The Journal of Experimental Medicine (1995)

Erythroblastic islands are anatomical units consisting of a central macrophage surrounded by erythroblasts. We studied the adhesion molecules involved in the formation of these structures. Central macrophages of erythroblastic islands isolated from the spleens of phlebotomized mice were clearly stained for vascular cell adhesion molecule 1 (VCAM-1). The surrounding erythroblasts of the erythroblastic islands strongly expressed the alpha 4 integrin of very late activation antigen 4 (VLA-4: alpha 4 beta 1 integrin), the counter receptor of VCAM-1, whereas most reticulocytes and erythrocytes did not. Both monoclonal antibodies (mAbs) against alpha 4 integrin and VCAM-1 disrupted the erythroblastic islands cultured in the presence of erythropoietin. Moreover, adhesion of splenic erythroblasts to tumor necrosis factor alpha-stimulated mouse splenic endothelial cells, which showed high expression of VCAM-1 but not intercellular adhesion molecule 1, was inhibited by the anti-VCAM-1 and anti-alpha 4 mAbs. These findings suggest that VLA-4-VCAM-1 interaction plays a crucial role in the formation of erythroblastic islands.
Does the Relation of Blood Pressure to Coronary Heart Disease Risk Change With Aging?
Authors: Stanley S. Franklin, Martin G. Larson, Shehzad A. Khan, Nathan D. Wong, Eric P. Leip, William B. Kannel, Daniel Levy
Journal: Circulation (2001)

Background —We examined the relative importance of diastolic (DBP), systolic (SBP) and pulse pressure (PP) as predictors of coronary heart disease (CHD) risk in different age groups of Framingham Heart Study participants. Methods and Results —We studied 3060 men and 3479 women between 20 and 79 years of age who were free of CHD and were not on antihypertensive drug therapy at baseline. Cox regression adjusted for age, sex, and other risk factors was used to assess the relations of BP indexes to CHD risk over a 20-year follow-up. In the group &lt;50 years of age, DBP was the strongest predictor of CHD risk (hazard ratio [HR] per 10 mm Hg increment, 1.34; 95% CI, 1.18 to 1.51) rather than SBP (HR, 1.14; 95% CI, 1.06 to 1.24) or PP (HR, 1.02; 95% CI, 0.89 to 1.17). In the group 50 to 59 years of age, risks were comparable for all 3 BP indexes. In the older age group, the strongest predictor of CHD risk was PP (HR, 1.24; 95% CI, 1.16 to 1.33). When both SBP and DBP were considered jointly, the former was directly and the latter was inversely related to CHD risk in the oldest age group Conclusions —With increasing age, there was a gradual shift from DBP to SBP and then to PP as predictors of CHD risk. In patients &lt;50 years of age, DBP was the strongest predictor. Age 50 to 59 years was a transition period when all 3 BP indexes were comparable predictors, and from 60 years of age on, DBP was negatively related to CHD risk so that PP became superior to SBP.
Phase II Study of Asparagine-Glycine-Arginine–Human Tumor Necrosis Factor α, a Selective Vascular Targeting Agent, in Previously Treated Patients With Malignant Pleural Mesothelioma
Authors: Vanesa Gregorc, Paolo A. Zucali, Armando Santoro, Giovanni L. Ceresoli, Giovanni Citterio, Tommaso M. De Pas, Nicoletta Zilembo, Fabio De Vincenzo, Matteo Simonelli, Gilda Rossoni, Anna Spreafico, Maria Grazia Viganò, Floriana Fontana, Filippo G. De Braud, Emilio Bajetta, Federico Caligaris-Cappio, Paolo Bruzzi, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2010)

NGR-hTNF consists of human tumor necrosis factor alpha (hTNF-alpha) fused to the tumor-homing peptide asparagine-glycine-arginine (NGR) able to selectively bind an aminopeptidase N isoform overexpressed on tumor blood vessels. Hypervascularity is a prominent and poor-prognosis feature of malignant pleural mesothelioma (MPM). Currently, there are no standard options for patients with MPM who are failing a front-line pemetrexed-based regimen. We explored safety and efficacy of NGR-hTNF in this setting.Eligible patients had radiologically documented tumor progression and performance status < or = 2. Primary study aim was progression-free survival (PFS). NGR-hTNF 0.8 microg/m(2) was given intravenously every 3 weeks. A subsequent cohort of patients received 0.8 microg/m(2) on a weekly basis.In the triweekly cohort (n = 43), only one grade 3 drug-related toxicity was noted, and the most common grades 1 to 2 were short-lived chills (71%). The median PFS was 2.8 months (95% CI, 2.3 to 3.3 months). Nineteen patients (44%) had disease control (one had partial response, and 18 had stable diseases) and experienced a median progression-free time of 4.4 months. In the weekly cohort (n = 14), there was no higher toxicity, and median PFS was 3.0 months (95% CI, 1.9 to 4.1 months). Seven patients (50%) had disease control (all stable diseases) and had a median progression-free interval of 9.1 months. In the overall study population (N = 57), median PFS was 2.8 months. Median progression-free time was 4.7 months in twenty-six patients (46%) who achieved disease control. Median survival was 12.1 months.The tolerability and disease control of NGR-hTNF 0.8 microg/m(2) weekly warrant additional evaluation in patients with advanced MPM.
Localization of the binding site of tissue-type plasminogen activator to fibrin.
Authors: A Ichinose, K Takio, K Fujikawa
Journal: Journal of Clinical Investigation (1986)

Functionally active A and B chains were separated from a two-chain form of recombinant tissue-type plasminogen activator after mild reduction and alkylation. The A chain was found to be responsible for the binding to lysine-Sepharose or fibrin and the B chain contained the catalytic activity of tissue-type plasminogen activator. An extensive reduction of two-chain tissue-type plasminogen activator, however, destroyed both the binding and catalytic activities. A thermolytic fragment, Fr. 1, of tissue-type plasminogen activator that contained a growth factor and two kringle segments retained its lysine binding activity. Additional thermolytic cleavages in the kringle-2 segment of Fr. 1 caused a total loss of the binding activity. These results indicated that the binding site of tissue-type plasminogen activator to fibrin was located in the kringle-2 segment.
Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands: a cohort study
Authors: EM Hoogerwaard, E Bakker, PF Ippel, JC Oosterwijk, DF Majoor-Krakauer, NJ Leschot, AJ Van Essen, HG Brunner, PA van der Wouw, AAM Wilde, M de Visser
Journal: The Lancet (1999)
Dendritic cells and immune regulation in the liver
Authors: A H Lau
Journal: Gut (2003)

Hepatic dendritic cells (DC) unquestionably play important roles in the induction and regulation of immune responses. Due to their paucity, functional characterisation of these important antigen presenting cells has been slow but use of DC growth factors (in particular GM-CSF and Flt3L) that markedly enhance their numbers has proved helpful in furnishing adequate study material. While there is growing evidence that DC function is affected in the pathogenesis of liver disease, most work to date has been performed on non-hepatic DC. Increasing knowledge of hepatic DC biology is likely to improve our understanding of disease pathogenesis and resistance to and therapy of liver disease.
Estrogen promotes stemness and invasiveness of ER-positive breast cancer cells through Gli1 activation
Authors: Ying Sun, Yunshan Wang, Cong Fan, Peng Gao, Xiuwen Wang, Guangwei Wei, Junmin Wei
Journal: Molecular Cancer (2014)

Abstract Background Although long-term estrogen (E2) exposure is associated with increased breast cancer (BC) risk, and E2 appears to sustain growth of BC cells that express functional estrogen receptors (ERs), its role in promoting BC stem cells (CSCs) remains unclear. Considering that Gli1, part of the Sonic hedgehog (Shh) developmental pathway, has been shown to mediate CSCs, we investigated whether E2 and Gli1 could promote CSCs and epithelial-mesenchymal transition (EMT) in ER + BC cell lines. Methods We knocked down Gli1 in several BC cells using a doxycycline-controlled vector, and compared Gli1 -knockdown cells and Gli1 + cells in behavior and expression of ER, Gli1, ALDH1 (BC-CSC marker), Shh, Ptch1 (Shh receptor) and SOX2, Nanog and Bmi-1 (CSC-associated transcriptions factors), using PCR; tissue microarrays, western blot; chromatin immunoprecipitation q-PCR, confocal immunofluorescence microscopy; fluorescence-activated cell sorting; annexin–flow cytometry (for apoptosis); mammosphere culture; and colony formation, immunohistochemistry, Matrigel and wound-scratch assays. Results Both mRNA and protein expressions of ER correlated with those of Gli1 and ALDH1. E2 induced Gli1 expression only in ER + BC cells. E2 promoted CSC renewal, invasiveness and EMT in ER + /Gli1 + cells but not in Gli1 -knockdown cells. Conclusions Our results indicate that estrogen acts via Gli1 to promote CSC development and EMT in ER + BC cells. These findings also imply that Gli1 mediates cancer stem cells, and thus could be a target of a novel treatment for ER + breast cancer.
RNA Synthesis in Ascites Hepatoma AH-130 Cells of Rats
Authors: Tetsuya Fukuda, Takiko Akino, Minoru Amano, Mitsuo Izawa
Journal: Cancer Research (1970)

The cellular components that were isolated from Ascites Hepatoma AH-130 cells were cytoplasm, nuclei, chromatin, nuclear sap, and nucleoli. The RNA/DNA ratio of isolated nuclei was 0.36. The isolated nucleoli contained about equal amounts of RNA and DNA. The nucleus of the hepatoma cells contained more RNA than the normal rat liver cell nucleus, especially in the nucleolus.

The RNA's were extracted from these cellular components, and their sedimentation classes were determined by sucrose density gradient centrifugation and by their nucleotide composition. RNA sedimenting faster than 28 S ribosomal RNA was detectable in the nucleoli. In the chromatin and nuclear sap fraction, small but significant amounts of RNA of an intermediate molecular size, between 18 S and 4 S, were found, as well as ribosomal and soluble RNA's.

Newly synthesized RNA in the nucleolus was the guanosine-cytosine-rich ribosomal-type RNA, with a sedimentation coefficient greater than 28 S. On the other hand the RNA synthesized in the chromatin fraction was adenosineuridine rich.

About 50 and 36% of the newly synthesized RNA were found in nucleoli isolated from 5-day-old and 7-day-old ascites hepatoma cells, respectively. These results indicate that ribosomal RNA synthesis was very active in the rapidly proliferating hepatoma cells.
Impact of social support programme on MDR-TB patients' treatment outcomes
Authors: Vadim Testov, Sergey Sterlikov, Irina Vasilyeva, Vladislav Erokhin, Teresa Kasayeva
Journal: European Respiratory Journal (2014)

Objective To define impact of social support programme on MDR-TB patients' treatment outcomes

Introduction 5.206 MDR-TB patients were enrolled for treatment in civilian sector of 26 Russian regions in 2008 -2010 within GF Round 4 project. The GF Round 4 project implemented social support programme as tool to increase TB patients' adherence. Patients on outpatient treatment received weekly food and hygienic sets. The cost of sets comprised 20 $US per month/per capita. 3.738 MDR-TB patients (including 1.328 new cases, 602 relapses and 1.808 - from other groups of retreatments) were covered by the social programme and 1.468 patients (including 455 new cases, 228 relapses and 785 from other groups of retreatmnets) didn't receive social support due to termination of GF Round 4 project.

Results. Treatment success rate comprised 50.7% for covered by social support programme MDR-TB patients and 47.2% for patients who didn't received social support (p=0.03). There were no different in treatment success and default rates between new MDR-TB cases and relapses who received and who didn't receive social support (p>0,1). Other retreatments (including patients from registration groups: treatment after default, treatment after failure of category I and II and other) showed reliable different in default rate - 21.3% for patients who received social support component and 28.4% for patients treated without social support component (p<0,01).

Conclusion. Presented model of social support programme demonstrated improvement of patients' adherence only for retreatments with treatment problems in the past. Impact of this model on treatment outcomes of new MDR-TB cases and relapses was not found.
Nuclear bridging of erythroblasts in acquired dyserythropoiesis: An early and transient preleukemic marker
Authors: Nicholas C. Bethlenfalvay, T. A. J. Phaure, Robert L. Phyliky, Robert P. Bowman
Journal: American Journal of Hematology (1986)

Abstract The clinical, hematologic, and histological characteristics of two patients who progressed from refractory anemia to acute leukemia are described. When first studied, nuclear bridging of erythroblasts, similar to that seen in congenital dyserythropoietic anemia type I and megakaryocytic dysplasia, were the only abnormalities. Within 6 years, both patients died, the first of acute nonlymphocytic leukemia, the second of erythroleukemia. Nuclear bridging of erythroblasts in the marrrow of these patients was an early and transient phenomenon and was not observed during the terminal phase of leukemia.
Changes in Treatment Adherence and Glycemic Control During the Transition to Adolescence in Type 1 Diabetes
Authors: Joseph R. Rausch, Korey K. Hood, Alan Delamater, Jennifer Shroff Pendley, Jennifer M. Rohan, Grafton Reeves, Lawrence Dolan, Dennis Drotar
Journal: Diabetes Care (2012)

To test models of unidirectional and bidirectional change between treatment adherence and glycemic control in youth with type 1 diabetes.We conducted a 2-year longitudinal, multisite study of 225 youth with type 1 diabetes recruited at the cusp of adolescence (aged 9-11 years) to describe the mutual influences of glycemic control as measured by HbA(1c) and treatment adherence as measured by blood glucose monitoring frequency (BGMF) during the transition to adolescence.HbA(1c) increased from 8.2 to 8.6% (P < 0.001) and BGMF decreased from 4.9 to 4.5 checks per day (P < 0.02) during the 2-year period. Changes in the BGMF slope predicted changes in HbA(1c). A change (increase) in HbA(1c) was associated with a change (decrease) in BGMF of 1.26 (P < 0.001) after controlling for covariates.The magnitude of the effect of declining treatment adherence (BGMF) on glycemic control in young adolescents may be even greater than declines observed among older adolescents. BGMF offers a powerful tool for targeted management of glycemic control for type 1 diabetes during the critical transition to adolescence.
Second Note on Parasitic Protozoa in Cancerous Tumours
Authors: M. A. Ruffer
Journal: BMJ (1892)

meDCLJouRL 993 sudden dyspnwa.He became rapidly cyanosed, and appeared as if likely to die.Accordingly the house physician performed venesection, and re- moved 8 ounces of blood from the arm.The relief was immediate, the urgent symptoms passed off, and the patient fell asleep and slept com- fortably for some hours.When the patient died, two days later, the right lung was found to contain several recent infarcts, probably formed abouit the time of the attack of dyspnoea.The patlhological condition explains the dyspnea and accounts for the relief obtained by the bleeding.CASE vI.Aortic Disease: Sudden Dyspnea: Venesection : PermanenfRelieft-The most striking case of this category I published in the Lancet in the year 1886.The patient, a labourer, about 40 years of age, was admitted with cardiac failure.The large area of cardiac dulness and the iindefinite character of the murmurs suggested the presence of a large pericardial effusion; but after a few hours' rest in the hospital it was evident that the lesion was double aortic disease with extreme dilatation.
Absence of Epstein-Barr virus carrying cells in synovial membranes and subcutaneous nodules of patients with rheumatoid arthritis.
Authors: P Brousset, M Caulier, A Cantagrel, C Dromer, B Mazieres, G Delsol
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To determine whether the Epstein-Barr virus is present in synovial membranes and subcutaneous nodules of patients with rheumatoid arthritis. METHODS--A sensitive in situ hybridisation technique was applied to tissue sections of 11 synovial membranes and five rheumatoid nodules. RESULTS--Cells carrying the Epstein-Barr virus were not detected using EBER and BHLF1 oligonucleotides in the tissue samples investigated here. CONCLUSIONS--Although it has been suggested that the Epstein-Barr virus could play a part in the aetiology of rheumatoid arthritis, it was not detected in synovial membranes and subcutaneous lesions in this study.
Trolox Attenuates Mechanical Ventilation–induced Diaphragmatic Dysfunction and Proteolysis
Authors: Jenna L. Betters, David S. Criswell, R. Andrew Shanely, Darin Van Gammeren, Darin Falk, Keith C. DeRuisseau, Melissa Deering, Tossaporn Yimlamai, Scott K. Powers
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Prolonged mechanical ventilation results in diaphragmatic oxidative injury, elevated proteolysis, fiber atrophy, and reduced force-generating capacity. We tested the hypothesis that antioxidant infusion during mechanical ventilation would function as an antioxidant to maintain redox balance within diaphragm muscle fibers and therefore prevent oxidative stress and subsequent proteolysis and contractile dysfunction. Sprague-Dawley rats were anesthetized, tracheostomized, and mechanically ventilated with 21% O(2) for 12 hours. The antioxidant Trolox was intravenously infused in a subset of ventilated animals. Compared with acutely anesthetized, nonventilated control animals, mechanical ventilation resulted in a significant reduction (-17%) in diaphragmatic maximal tetanic force. Importantly, Trolox completely attenuated this mechanical ventilation-induced diaphragmatic contractile deficit. Total diaphragmatic proteolysis was increased 105% in mechanical ventilation animals compared with controls. In contrast, diaphragmatic proteolysis did not differ between controls and mechanical ventilation-Trolox animals. Moreover, 20S proteasome activity in the diaphragm was elevated in the mechanical ventilation animals (+76%); Trolox treatment attenuated this mechanical ventilation-induced rise in protease activity. These results are consistent with the hypothesis that mechanical ventilation-induced oxidative stress is an important factor regulating mechanical ventilation-induced diaphragmatic proteolysis and contractile dysfunction. Our findings suggest that antioxidant therapy could be beneficial during prolonged mechanical ventilation.
Differential Requirement for DNA Methyltransferase 1 in Maintaining Human Cancer Cell Gene Promoter Hypermethylation
Authors: Angela H. Ting, Kam-wing Jair, Kornel E. Schuebel, Stephen B. Baylin
Journal: Cancer Research (2006)

Abstract Previous work has shown that DNA hypermethylation of tumor suppressor genes in colorectal cancer cells may be maintained in the absence of the major mammalian methyltransferase, DNA methyltransferase 1 (DNMT1). In an effort to dissect the dependency on DNMT1 to maintain such hypermethylation in different cancer types, we performed a systematic analysis of depletion of DNMT1 in colorectal (SW48), bladder (T24), and breast (T47D) cancer cells by DNMT1-specific small hairpin RNA (shRNA) targeting. We show that although DNMT1-deficient SW48 and T24 cells exhibited no observable growth defects and were able to maintain promoter hypermethylation, DNMT1-deficient T47D breast cells failed to form comparable numbers of colonies when stably selected for the incorporation of the DNMT1-specific shRNA expression vector, suggesting a growth defect with reduced levels of DNMT1. Further treatment of T47D cells with transient transfection of small interfering RNA targeting DNMT1 revealed that severely DNMT1-deficient T47D cells could not fully maintain promoter hypermethylation, and gene silencing was partially reversed at two of the three assayed loci. These observations suggest that human cancer cells may differ in their reliance on DNMT1 for maintaining DNA methylation. (Cancer Res 2006; 66(2): 729-35)