tbuckley/cabot-search huggingface dataset:
Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment
Authors: Uma Malhotra, Sarah Holte, Sujay Dutta, M. Michelle Berrey, Elizabeth Delpit, David M. Koelle, Alessandro Sette, Lawrence Corey, M. Juliana McElrath
Journal: Journal of Clinical Investigation (2001)

HIV-1–infected patients treated early with combination antiretrovirals respond favorably, but not all maintain viral suppression and improved HIV-specific Th function. To understand if genetic factors contribute to this variation, we prospectively evaluated over 18 months 21 early-treated patients stratified by alleles of class II haplotypes. All seven subjects with the DRB1*13-DQB1*06 haplotype, but only 21% of other subjects, maintained virus suppression at every posttreatment measurement. Following HIV-1 p24 antigen stimulation, PBMCs from patients with this haplotype demonstrated higher mean lymphoproliferation and IFN-γ secretion than did cells from patients with other haplotypes. Two DRB1*13-restricted Gag epitope regions were identified, a promiscuous one that bound its putative restriction element with nanomolar affinity, and another that mapped to a highly conserved region. These findings suggest that class II molecules, particularly the DRB1*13 haplotype, have an important impact on virologic and immunologic responses. The advantage of the haplotype may relate to selection of key HIV-1 Th1 epitopes in highly conserved regions with avid binding to class II molecules. Eliciting responses to the promiscuous epitope region may be beneficial in vaccine strategies.
K-Ras Nanoclustering Is Subverted by Overexpression of the Scaffold Protein Galectin-3
Authors: Ruby Shalom-Feuerstein, Sarah J. Plowman, Barak Rotblat, Nicholas Ariotti, Tianhai Tian, John F. Hancock, Yoel Kloog
Journal: Cancer Research (2008)

Abstract The spatial organization of K-Ras proteins into nanoclusters on the plasma membrane is essential for high-fidelity signal transduction. The mechanism underlying K-Ras nanoclustering is unknown. We show here that K-Ras.GTP recruits Galectin-3 (Gal-3) from the cytosol to the plasma membrane where it becomes an integral nanocluster component. Importantly, we show that the cytosolic level of Gal-3 determines the magnitude of K-Ras.GTP nanoclustering and signal output. The β-sheet layers of the Gal-3 carbohydrate recognition domain contain a hydrophobic pocket that may accommodate the farnesyl group of K-Ras. V125A substitution within this hydrophobic pocket yields a dominant negative Gal-3(V125A) mutant that inhibits K-Ras activity. Gal-3(V125A) interaction with K-Ras.GTP reduces K-Ras.GTP nanocluster formation, which abrogates signal output from the Raf/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) pathway. Gal-3(V125A) negatively regulates cell growth and reduces cellular transformation. Thus, regulation of K-Ras nanocluster formation and signal output by Gal-3 critically depends on the integrity of the Gal-3 hydrophobic pocket. These results show that Gal-3 overexpression in breast cancer cells, which increases K-Ras signal output, represents oncogenic subversion of plasma membrane nanostructure. [Cancer Res 2008;68(16):6608–16]
Intussusception of Appendiceal Adenoma Mimicking Invasive Carcinoma
Authors: Y. J. Kawamura, N. Toyama, T. Kasamatsu, M. Ota, F. Konishi
Journal: Endoscopy (2002)

A 73-year-old man presented with lower abdominal pain. The physical examination revealed a right lower abdominal mass about 6 cm in diameter, without peritoneal signs. Abdominal ultrasonography and computed tomography revealed a "target sign" in the right lower abdomen, and intussusception was therefore strongly suspected. The right lower abdominal mass was not palpable 1 week later, when colonoscopy was performed. Colonoscopy demonstrated a protruding mass 2 cm in diameter in the cecum (Figure [1]). The orifice of the appendix was not seen. The surface of the tumor was irregular; a depression was present on the top of the tumor, and there was a slight protrusion within the depression. Submucosal invasion was therefore suspected. Magnifying colonoscopy with dye spraying revealed an irregular pattern of colonic pits (Figure [2]), which also suggested submucosal invasion.
Regulating the collection and use of fetal stem cells
Authors: Julie Kent, Naomi Pfeffer
Journal: BMJ (2006)

They currently lie in a regulatory limbo 

T he British government is committed to supporting stem cell science and industry.1 An important part of that commitment is a strong regulatory environment, seen as being embodied in the Human Fertilisation and Embryology Authority (HFEA), which oversees a strict but permissive regulatory framework and contains public concerns about the use in research and treatment of human embryos. However, the HFEA regulates only the use of embryos created in vitro. It has no jurisdiction over the use of aborted fetuses, which are still subject to guidelines drawn up 17 years ago and have been neglected in recent discussions around stem cell research.

Sustaining in vitro a human embryo beyond 14 days is legally and technically impossible, so investigators seeking embryonic material older than 14 days usually collect it after abortion (or, less often, after miscarriage or surgery for an ectopic pregnancy). The collection and use of aborted fetuses has been governed …
Junctional adhesion molecule C (JAM-C) distinguishes CD27+ germinal center B lymphocytes from non-germinal center cells and constitutes a new diagnostic tool for B-cell malignancies
Authors: C Ody, S Jungblut-Ruault, D Cossali, M Barnet, M Aurrand-Lions, B A Imhof, T Matthes
Journal: Leukemia (2007)
Reproducibility of Coronary Flow Reserve (CFR) Measurement with Rubidium-82 PET Perfusion Imaging
Authors: R Matthews, I M Youssef, K Bukala, M Quispe, C K Kim, B R Krynyckyi, J Machac
Journal: Clinical Nuclear Medicine (2005)

Greater New York and New England Chapters, the Society of Nuclear Medicine 18th Annual Northeast Regional Scientific Session Abstracts October 22–October 24, 2004—Stamford, Connecticut: PDF Only
The Limits of Medical Care
Authors: Robert J. Haggerty
Journal: New England Journal of Medicine (1985)

Fuchs, in his provocative book Who Shall Live,1 estimates that the presence or absence of medical care accounts for only 10 per cent of the differences in mortality between different populations. Genetics, health habits, and that vague, yet powerful factor, social class, account for the majority of the differences.Health services policy during the past two decades has largely been occupied with achieving equity of access to medical care for people with previously low rates of access. Neighborhood health centers, Medicaid, and special maternal and child health projects have resulted in approximate equality of use by different socioeconomic groups. . . .
Morphologic diagnosis of thrombotic thrombocytopenic purpura
Authors: Edward R. Burns, Yenmay Lou, Anjali Pathak
Journal: American Journal of Hematology (2003)

The diagnosis of thrombotic thrombocytopenic purpura (TTP) rests on evidence of microangiopathic hemolytic anemia and thrombocytopenia in the absence of disseminated intravascular coagulation and other known causes of thrombotic microangiopathy. Highly specific diagnostic tools such as serum levels of ADAMTS13 are not routinely available for immediate clinical diagnosis. The presence of schistocytes on a blood smear is the morphologic hallmark of the disease, but no guidelines exist as to the number of schistocytes required to differentiate TTP from other thrombotic microangiopathies. We studied 6 patients with TTP and compared their schistocyte counts with those of 40 normal subjects, 28 patients with chronic renal disease, 5 with preeclampsia, and 5 with normal functioning mechanical heart valves. The mean schistocyte count for the TTP patients was 8.35% versus 0.05% for normal subjects, 0.2% for renal patients, 0.25% for preeclamptic patients, and 0.18% for patients with mechanical valves (P < 0.001). Schistocytes were found on 100% of blood films of TTP patients and ranged from 1.0% to 18.4% of red cells. Schistocytes are found on the smears of 58% of normal individuals and on 80-100% of the other patient groups studied, but always comprise less than 0.5% of the red cell population. An initial schistocyte count of greater than 1% strongly suggests a diagnosis of TTP in the absence of other known causes of thrombotic microangiopathy.
Manual of Clinical Microbiology
Authors: Victor Lorian
Journal: JAMA (1991)

In his introduction, Balows, editor-in-chief of the<i>Manual of Clinical Microbiology</i>, fifth edition, states that this book could be a reference book, a textbook, or a laboratory manual. I think it qualifies for all three. The text contains an unprecedented amount of information, which has been updated and expanded from the 1985 fourth edition. The contributing authors consist of experts in the respective fields, many of whom developed by their own research the areas they authored. The first of ten sections describes general aspects such as specimen collection, quality assurance, and laboratory safety. The chapter on the assessment of new technology is mostly devoted to the determination of the predictive value of tests, defining their quality and their role for the care of patients. This chapter is invaluable for the physician who must select the most appropriate test for diagnosing illness or screening for infection. Section two reviews in detail
James Brunskill Brierley
Authors: D I Graham
Journal: BMJ (2004)

Former scientific officer MRC neuropsychiatry unit, MRC laboratories, Carshalton, and honorary consultant in neuropathology West Park Hospital, Epsom (b 1916; q Bristol 1944; MD, FRCPath, FRCPsych), d 19 January 2004.​2004.




Figure 1




In 1964 Jim was appointed head of a research team concerned with the physiological and neuropathological investigation of brain damage resulting from hypoxia. He published some 150 manuscripts and took part in seminal work with RAF Farnborough to determine the optimal window size of Concorde in the event of a blowout. During his most successful scientific years he designed and undertook studies that defined the relationship between the brain and the heart in terms of which of these two organs was the most vulnerable to conditions of hypoxia. He leaves a wife, Lorna; two children; and three grandchildren.
IMPACT OF MYOCARDIAL VIABILITY ON ECHOCARDIOGRAPHIC PARAMETERS OF CARDIAC STRUCTURE AND FUNCTION IN PATIENTS WITH ISCHEMIC CARDIOMYOPATHY. A REPORT FROM THE STICH TRIAL
Authors: Federico M. Asch, Thomas A. Holly, Lilin She, Gerald Maurer, Jacek Myc, William A. Zoghbi, Anna Teresinska, Bozena Birkenfeld, Eric J. Velazquez, Patricia A. Pellikka, Christopher Adlbrecht, Robert O. Bonow, Julio A. Panza
Journal: Journal of the American College of Cardiology (2010)
Magnetic heating properties and neutron activation of tungsten-oxide coated biocompatible FePt core–shell nanoparticles
Authors: K.M. Seemann, M. Luysberg, Z. Révay, P. Kudejova, B. Sanz, N. Cassinelli, A. Loidl, K. Ilicic, G. Multhoff, T.E. Schmid
Journal: Journal of Controlled Release (2014)
784 CELL ENTRY FACTOR USAGE AND VIRAL EVASION IN HEPATITIS C VIRUS INFECTION IN VIVO
Authors: P. Carolla, I. Fofana, S. Fafi-Kremer, M.N. Zahid, K. Cury, M. Turek, M. Bastien-Valle, F.-L. Cosset, T. Pietschmann, J. Hayer, C. Combet, F. Habersetzer, M. Doffoël, Z.-Y. Keck, S.K.H. Foung, M.B. Zeisel, F. Stoll-Keller, T.F. Baumert
Journal: Journal of Hepatology (2011)
Prostaglandins evoke a whole variety of responses in the lung.
Authors: P J Kadowitz, E W Spannhake, A L Hyman
Journal: Environmental Health Perspectives (1980)

Rapid intravenous (IV) injections of the prostaglandin precursor arachidonic acid (AA) increase pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in a variety of species. It has recently been reported that infusions of AA decrease PAP. The purpose of this report is to contrast responses to bolus injections and infusions of AA in the anesthetized dog. In all experiments rapid IV injections of AA increased PAP and PVR; however, infusions of 68 to 680 microgram/min produced variable responses. In 10 of 19 animals, AA infusion decreased PAP and PVR, and this response was enhanced when pulmonary vascular tone was actively increased by vasoconstrictor agents or alveolar hypoxia. In the other nine animals, the predominant response was an increase in PAP and PVR. In all experiments infusions of larger amounts of AA (1.4 to 3.4 mg/min) increased PAP. Both pressor and depressor responses to AA were inhibited to meclofenamate. This study shows that infusion of small amounts of AA dilates or constricts the pulmonary vascular bed. In contrast, infusion of larger amounts of AA always causes vasoconstriction. These data suggest that at low infusion rate, PGI2, which is a vasodilator, is the predominant metabolite formed from AA in some animals. However, at higher concentrations, the production of constrictor products predominates. These experiments also suggest that the products formed and the response observed may be dependent on a number of factors including the amount of tone present in the pulmonary vascular bed.
Genetic Disorders of Man
Authors: Ian Shine
Journal: JAMA (1971)

This book achieves perfectly what it sets out to do, namely, to help medical students and physicians to understand those genetical disorders of man falling within the specialty of internal medicine. In fact, it does much more, since it provides a comprehensive account of most genetically determined diseases and abnormalities of man. For example, there are one or two pages on hemoglobin M, Chediak-Higashi syndrome, and antitrypsin deficiency, cri du chat syndrome, and inbreeding. Its comprehensiveness may deter medical students who find Porter's<i>Heredity and Disease</i>, or Thompson and Thompson's<i>Genetics in Medicine</i>, both good and sufficient, but its size, clarity, and strong clinical bias will make it the text of choice for all clinicians and, I hope, for all geneticists. After all, man has at last surplanted the fruit fly in genetical interest. The material is organized into two parts. There is an introductory section, with chapters on molecular
Prediction of Site-Specific Amino Acid Distributions and Limits of Divergent Evolutionary Changes in Protein Sequences
Authors: Markus Porto, H. Eduardo Roman, Michele Vendruscolo, Ugo Bastolla
Journal: Molecular Biology and Evolution (2004)

We derive an analytic expression for site-specific stationary distributions of amino acids from the Structurally Constrained Neutral (SCN) model of protein evolution with conservation of folding stability.The stationary distributions that we obtain have a Boltzmann-like shape, and their effective temperature parameter, measuring the limit of divergent evolutionary changes at a given site, can be predicted from a site-specific topological property, the principal eigenvector of the contact matrix of the native conformation of the protein.These analytic results, obtained without free parameters, are compared with simulations of the SCN model and with the sitespecific amino acid distributions obtained from the Protein Data Bank.These results also provide new insights into how the topology of a protein fold influences its designability, i.e. the number of sequences compatible with that fold.The dependence of the effective temperature on the principal eigenvector decreases for longer proteins, a possible consequence of the fact that selection for thermodynamic stability becomes weaker in this case.
Stress disorder is common among prostitutes
Authors: N. Macready
Journal: BMJ (1998)

In order to determine the significance of abnormalities of diastolic function in patients with left ventricular hypertrophy, exercise echocardiography to heart rates of 140 to 150 beats/min was performed in 18 normal subjects and 14 patients after aortic valve replacement. Simultaneous echo-, phono-, and electrocardiograms were recorded. Left ventricular cavity size was determined at end-diastole and end-systole. The timing of mitral valve opening and closure was measured, and hence left ventricular filling time derived, expressed either as ms/beat, or s/min when multiplied by heart rate. Isovolumic relaxation was taken as the interval between A2 and mitral valve opening. Systolic function, assessed from cavity dimensions, peak VCF, and QA2 interval was normal in all but two patients at rest and on exercise. Isovolumic relaxation was prolonged at rest in the patients to 85 +/- 8 ms (normal 69 +/- 9 ms), but left ventricular filling times were normal. With exercise, in normal subjects, isovolumic relaxation remained constant, but filling times dropped strikingly from 380 +/- 66 ms/beat, or 27 +/- 2 s/min at rest to 115 +/- 10 ms/beat or 16 +/- 2 s/min. In patients with left ventricular hypertrophy, isovolumic relaxation dropped on exercise to 41 +/- 15 ms. Filling periods were normal at rest, 367 +/- 67 ms/beat or 27 +/- 3 s/min, but failed to show the normal drop with exercise, being 240 +/- 44 ms/beat or 28 +/- 4 s/min. At heart rates above 120/min, separation between the two groups was complete. Thus, striking abnormalities of left ventricular filling can be demonstrated on exercise in patients with left ventricular hypertrophy. They appear to represent loss of mechanisms whereby rapid diastolic filling is achieved in the normal subject.
Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009.
Authors: L. Gubareva, M. Okomo-Adhiambo, V. Deyde, A. M. Fry, T. G. Sheu, R. Garten, C. Smith, J. Barnes, A. Myrick, M. Hillman, M. Shaw, C. Bridges, A. Klimov, N. Cox
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
Induction of gene expression by 5-Aza-2′-deoxycytidine in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) but not epithelial cells by DNA-methylation-dependent and -independent mechanisms
Authors: K Schmelz, N Sattler, M Wagner, M Lübbert, B Dörken, I Tamm
Journal: Leukemia (2004)
Therapeutic Effect of Intravenous Interferon Gene Delivery with Naked Plasmid DNA in Murine Metastasis Models
Authors: Naoki Kobayashi, Takeshi Kuramoto, Shi Chen, Yoshihiko Watanabe, Yoshinobu Takakura
Journal: Molecular Therapy (2002)

Interferons (IFNs) exhibit pleiotropic biological activities that are considered to play important roles in tumor suppression and rejection. Therefore, IFN genes are promising for in vivo cytokine gene therapy targeted against tumors. In the present study, we evaluated the efficacy of hydrodynamics-based IFN gene transfer for tumor treatment, in which the naked pDNA encoding IFN-β or IFN-γ was administered into the tail vein of mice following portal vein (liver metastasis), tail vein (lung metastasis), or subcutaneous injection (subcutaneous tumor) of mouse colon carcinoma CT-26 cells. A substantial amount of IFN was soon markedly expressed in the liver and a transient increase in IFN activity was detected in the circulation. This procedure caused transgene-specific IFN production with little induction of other proinflammatory cytokines. In the liver metastasis experiment, the mice treated with IFN-expressing pDNA displayed a profound reduction in liver metastasis and a prolonged survival. Administration of the pDNA at an earlier stage of metastasis was more crucial for the antitumor effect. Similar tumor suppression was seen in the lung metastasis experiment. These therapeutic effects were more marked with IFN-β-expressing pDNA treatment than with IFN-γ-expressing pDNA treatment. On the other hand, subcutaneous CT-26 tumor growth was hardly affected by pDNA administration. These results suggest that the hydrodynamics-based transfer of naked pDNA is a convenient and efficient method of IFN gene therapy against metastatic tumors.
Effect of Different Periods of Fasting on Oral Glucose Tolerance
Authors: C. H. Walsh, J. O'Regan, D. J O'Sullivan
Journal: BMJ (1973)

The effect of different periods of fasting on oral glucose tolerance was investigated in 33 subjects. It was found that glucose tolerance deteriorated as the fasting period became shorter. This effect was seen almost exclusively in subjects over 40 years of age. Only the fasting blood sugar was affected by the duration of the pretest fast in younger subjects.
Effect of Folic Acid and B Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease
Authors: Christine M. Albert, Nancy R. Cook, J. Michael Gaziano, Elaine Zaharris, Jean MacFadyen, Eleanor Danielson, Julie E. Buring, JoAnn E. Manson
Journal: JAMA (2008)

Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials.To test whether a combination of folic acid, vitamin B6, and vitamin B12 lowers risk of CVD among high-risk women with and without CVD.Within an ongoing randomized trial of antioxidant vitamins, 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive a combination pill containing folic acid, vitamin B6, and vitamin B12 or a matching placebo, and were treated for 7.3 years from April 1998 through July 2005.Daily intake of a combination pill of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12.A composite outcome of myocardial infarction, stroke, coronary revascularization, or CVD mortality.Compared with placebo, a total of 796 women experienced a confirmed CVD event (406 in the active group and 390 in the placebo group). Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point (226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group; relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.19; P = .65), as well as for the secondary outcomes including myocardial infarction (34.5/10,000 person-years vs 39.5/10,000 person-years; RR, 0.87; 95% CI, 0.63-1.22; P = .42), stroke (41.9/10,000 person-years vs 36.8/10,000 person-years; RR, 1.14; 95% CI, 0.82-1.57; P = .44), and CVD mortality (50.3/10,000 person-years vs 49.6/10,000 person-years; RR, 1.01; 95% CI, 0.76-1.35; P = .93). In a blood substudy, geometric mean plasma homocysteine level was decreased by 18.5% (95% CI, 12.5%-24.1%; P < .001) in the active group (n = 150) over that observed in the placebo group (n = 150), for a difference of 2.27 micromol/L (95% CI, 1.54-2.96 micromol/L).After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.clinicaltrials.gov Identifier: NCT00000541.