tbuckley/cabot-search huggingface dataset:
Efficient loading of identical viral peptide onto class II molecules by antigenized immunoglobulin and influenza virus.
Authors: T D Brumeanu, W J Swiggard, R M Steinman, C A Bona, H Zaghouani
Journal: The Journal of Experimental Medicine (1993)

Several prior reports have identified peptides that are naturally associated with major histocompatibility complex (MHC) class II molecules on presenting cells. We have examined the delivery of a peptide from exogenous sources to MHC class II molecules. The peptide derives from the influenza virus hemagglutinin (HA) and activates a CD4+ T cell hybridoma. In functional assays of antigen presentation, this epitope is delivered effectively to T cells either in the context of influenza virus or chimeric immunoglobulin (Ig) molecules (Ig-HA) in which the peptide has replaced the CDR3 loop of the heavy chain. We find that the identical 11-mer peptide can be isolated from mouse MHC class II antigens whether the exogenous source of peptide is free HA peptide, the Ig-HA chimera, or ultraviolet-inactivated PR8 influenza virus. The Ig-HA chimera proves to be the most efficient vehicle for charging class II molecules via the exogenous route. Given the fact that self Igs represent natural long-lived carriers, we suggest that antigenized Igs have considerable potential for peptide delivery to MHC molecules in situ.
Abciximab reduces urgent target vessel revascularization at 30 days after primary angioplasty, independently of acute angiographic results. The RAPPORT trial
Authors: S.J. Brener, L.A. Barr, E.D. Cohen, H.J. White, D.J. Moliterno, H.B. Cheek, M.B. Effron, E.J. Topol
Journal: Journal of the American College of Cardiology (1998)
Endothelin-1 receptor A blocker darusentan decreases hepatic changes and improves liver repopulation after cell transplantation in rats
Authors: Ralf Bahde, Sorabh Kapoor, Preeti Viswanathan, Hans-Ullrich Spiegel, Sanjeev Gupta
Journal: Hepatology (2013)

Cell transplantation-induced hepatic ischemia and recruitment of vasoconstrictors (e.g., endothelin-1; Edn1) leads to clearance of transplanted cells and poses problems for liver repopulation. Therefore, we determined whether darusentan (DAR), which potently blocks Edn1 receptor type A, could benefit cell engraftment. We transplanted primary F344 rat hepatocytes with or without DAR in dipeptidyl peptidase IV-deficient rats. Analysis of microcirculatory events included hepatic ischemia, endothelial injury, including with gene expression arrays, and activations of Kupffer cells (KCs), neutrophils, or hepatic stellate cells (HSCs). The retrorsine-partial hepatectomy model was used for liver repopulation studies. Whether DAR was directly cytoprotective was examined in cultured rat hepatocytes or CFSC-8B rat HSCs. We found that DAR induced hepatic sinusoidal vasodilation, caused more transplanted cells to be deposited in liver parenchyma, and decreased hepatic ischemia and endothelial injury. This lessened perturbations in expression of endothelial biology genes, including regulators of vessel tone, inflammation, cell adhesion, or cell damage, versus drug-untreated controls. Moreover, in DAR-treated animals, cell transplantation-induced activation of KCs, albeit not of neutrophils, decreased, and fewer HSCs expressed desmin. In DAR-treated rats, improvements in cell engraftment led to greater extent of liver repopulation, compared to drug-untreated controls. In cell-culture assays, DAR did not stimulate release of cytoprotective factors, such as vascular endothelial growth factor, from HSCs. Moreover, DAR did not protect hepatocytes from tumor necrosis factor alpha- or oxidative stress-induced toxicity. Endothelin receptor A blockade in vitro did not improve engraftment of subsequently transplanted hepatocytes.Systemic administration of DAR decreases hepatic ischemia-related events and thus indirectly improves cell engraftment and liver repopulation. This vascular mechanism may permit the development of combinatorial drug-based regimens to help optimize cell therapy.
Transurethrale Entfernung eines großen Konkrements aus einer Ureterozele
Authors: A. Angeloff
Journal: Endoscopy (1971)

The endoscopic treatment of an unusually big ureteral stone in an uretrocele is described. After an electrical incision of the ureterocele the stone could be transurethrally crushed and spontaneously removed by miction owing to the newly developed electric lithotripsy.
Performance of functionally graded implants of polylactides and calcium phosphate/calcium carbonate in an ovine model for computer assisted craniectomy and cranioplasty
Authors: Harald Eufinger, Christian Rasche, Jutta Lehmbrock, Michael Wehmöller, Stephan Weihe, Inge Schmitz, Carsten Schiller, Matthias Epple
Journal: Biomaterials (2006)
Soluble E-selectin, leptin, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients
Authors: Ataru Taniguchi, Mitsuo Fukushima, Yoshikatsu Nakai, Akira Kuroe, Gen Yamano, Takiko Yanagawa, Minako Ohgushi, Michihiro Ohya, Satoru Yoshii, Yoshiro Taki, Yutaka Seino
Journal: Metabolism (2005)
PWE-165 CYP2C19*17 gain of function mutation is associated with peptic ulcer disease
Authors: C O Musumba, D V Eker, A Jorgensen, D M Pritchard, M Pirmohamed
Journal: Gut (2012)

<h3>Introduction</h3> Studies show that single nucleotide polymorphisms (SNPs) in non-steroidal antiinflammatory drug (NSAID)-metabolising enzymes (mainly CYP2C9 and CYP2C8) may predispose NSAID-users to peptic ulcer disease (PUD) or upper gastrointestinal bleeding (UGIB), but results have been inconclusive. <h3>Methods</h3> We hypothesised that the eight closely-linked clinically important SNPs in the CYP2C family of genes, namely CYP2C8*3 (rs11572080 and rs10509681), CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17 predispose to PUD via impaired NSAID metabolism as well as other potentially important mechanisms (eg, metabolism of arachidonic acid (AA) and proton-pump inhibitors-PPIs). Subjects diagnosed with PUD/UGIB at 13 hospitals in the UK between 2005 and 2011 were recruited and interviewed using a structured questionnaire, and categorised as either NSAID-users or non-users. UGIB was defined as haematemesis, melaena or anaemia, and endoscopic stigmata of recent bleeding. <i>H pylori</i> status was ascertained in most subjects. Following extraction of genomic DNA, genotyping was performed by KBioscience Ltd (UK). Logistic regression analysis was used to test for association between each SNP and risk of PUD/UGIB. Interaction terms were introduced to determine whether any observed genetic effects were influenced by factors including type of NSAID, PPI use and gender. <h3>Results</h3> 1246 white patients were recruited and categorised as follows: 485 (39%) PUD+/NSAID+; 357 (29%) PUD+/NSAID-; 125 (10%) PUD−/NSAID+; 280 (22%) PUD−/NSAID−. Seven SNPs were included in the final analysis (CYP2C19*3 was monomorphic and excluded). All SNPs were in Hardy-Weinberg equilibrium. Logistic regression analysis of cases (PUD+; n=842) and controls (PUD−; n=405), assuming an additive mode of inheritance at each SNP, showed that only CYP2C19*17 was significantly associated with PUD (p=0.006), with suggestion of an allele-dose effect, even on classifying cases as those using only CYP2C9/CYP2C8-substrate NSAIDs (p=0.005). Post-hoc analysis showed no interaction between CYP2C19*17 and NSAID type, PPI use or gender. Subgroup analysis per ulcer type showed CYP2C19*17 was significantly associated with gastric ulcers (p=0.02), while only rs11572080 was associated with duodenal ulcers (p=0.04). No SNPs were associated with UGIB. <h3>Conclusion</h3> Possession of CYP2C19*17 allele is associated with PUD, especially gastric ulcers, regardless of aetiology. We postulate that this could be through its effect on the metabolism of AA or other endogenous substances, leading to impairment of gastrointestinal mucosal defences. Further studies are needed to correlate the functional consequences of CYP2C19*17 in the pathogenesis of PUD. <h3>Competing interests</h3> None declared.
Nephrotic Syndrome Due to Primary Renal Disease in Adults: II. A Controlled Trial of Prednisolone and Azathioprine
Authors: P. Sharpstone, C. S. Ogg, J. S. Cameron
Journal: BMJ (1969)

A controlled trial in 20 adult patients with the nephrotic syndrome due to proliferative glomerulonephritis compared the effects of consecutive eight-week courses of treatment with prednisolone in conventional dosage and a low-dose azathioprine–prednisolone combination. Though the azathioprine regimen avoided serious toxicity and produced a statistically significant improvement in creatinine clearance and urine protein excretion, the results were not significantly better than with prednisolone itself and overall were not of great clinical value. Prolongation of the azathioprine–prednisolone treatment to one year was associated with some small improvement in the results. The effectiveness of prednisolone in the nephritic syndrome of adults with minimal renal histological abnormality was confirmed by a complete loss of proteinuria within eight weeks in six out of eight patients and substantial reduction in the other two. These two patients subsequently received azathioprine as well but with equivocal results.
Natural cycle IVF should be used more frequently
Authors: P. Moore
Journal: BMJ (2001)

In vitro fertilisation treatment that does not involve ovarian stimulation could be a cost effective option for some infertile couples, a new study has concluded ( Human Reproduction 2001;16:221-5).

The researchers claim that not stimulating a woman's ovaries has several advantages: it is safer and less stressful, the treatment can be repeated over consecutive cycles, and it reduces the cost of each treatment cycle by up to 75%. They put the cost of unstimulated IVF at just under £400, and stimulated at £1717, the difference being accounted for by the extra drugs (£625) and extra monitoring to …
African parliamentarians commit to prioritising maternal and child health
Authors: P. Moszynski
Journal: BMJ (2011)

The Pan African Parliament—the legislative arm of the African Union—has adopted a resolution urging speakers of the continent’s 54 national parliaments to prioritise the implementation of maternal, newborn, and child health programmes.

The Africa Public Health Parliamentary Network says this development marks a “significant milestone” in accelerating Africa’s progress towards the attainment of the millennium development goals on child and maternal health.

In the resolution, passed during the fifth session of the second Pan African Parliament held on 3-14 October in Johannesburg, South Africa, members endorsed the commitments made …
Group-level traits can be studied with standard evolutionary theory
Authors: Thomas C. Scott-Phillips, Thomas E. Dickins
Journal: Behavioral and Brain Sciences (2014)

Abstract Smaldino's target article draws on and seeks to add to a literature that has partially rejected orthodox, gene-centric evolutionary theory. However, orthodox theory has much to say about group-level traits. The target article does not reference or refute these views, and provides no explicit arguments for this narrow approach. In this commentary we: (i) give two examples of topics that the target article might and probably should have discussed (cultural epidemiology and the psychology of individual differences); and (ii) argue that the orthodox approach has much more to say about the emergence of group-level traits than the target article recognises, or gives credit for.
Taking "ME" too personally
Authors: R. Morriss
Journal: BMJ (1996)

Esther Rantzen is angry. She is known mostly for light heartedly observing the absurdities of everyday life or exposing rascals who are not quite evil enough for the Cook Report. Occasionally she spearheads a big campaign against an important medical or social evil, such as child sexual abuse. This time the big campaign is “ME” because unfortunately her daughter has ME.

Typically, there is no attempt to give a balanced perspective, only exposure of the evil as if it were an open and shut case. Her current anger seems …
Surface Characteristics of Nanoparticles Determine Their Intracellular Fate in and Processing by Human Blood–Brain Barrier Endothelial Cells In Vitro
Authors: Julia V Georgieva, Dharamdajal Kalicharan, Pierre-Olivier Couraud, Ignacio A Romero, Babette Weksler, Dick Hoekstra, Inge S Zuhorn
Journal: Molecular Therapy (2010)

A polarized layer of endothelial cells that comprises the blood-brain barrier (BBB) precludes access of systemically administered medicines to brain tissue. Consequently, there is a need for drug delivery vehicles that mediate transendothelial transport of such medicines. Endothelial cells use a variety of endocytotic pathways for the internalization of exogenous materials, including clathrin-mediated endocytosis, caveolar endocytosis, and macropinocytosis. The different modes of endocytosis result in the delivery of endocytosed material to distinctive intracellular compartments and therewith correlated differential processing. To obtain insight into the properties of drug delivery vehicles that direct their intracellular processing in brain endothelial cells, we investigated the intracellular processing of fixed-size nanoparticles in an in vitro BBB model as a function of distinct nanoparticle surface modifications. Caveolar endocytosis, adsorptive-mediated endocytosis, and receptor-mediated endocytosis were promoted by the use of uncoated 500-nm particles, attachment of the cationic polymer polyethyleneimine (PEI), and attachment of prion proteins, respectively. We demonstrate that surface modifications of nanoparticles, including charge and protein ligands, affect their mode of internalization by brain endothelial cells and thereby their subcellular fate and transcytotic potential.
Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial
Authors: James Berenson, Robert Pflugmacher, Peter Jarzem, Jeffrey Zonder, Kenneth Schechtman, John B Tillman, Leonard Bastian, Talat Ashraf, Frank Vrionis
Journal: The Lancet Oncology (2011)
Coexistence of Arterial Compression in Patients With Neurogenic Thoracic Outlet Syndrome
Authors: Kendall Likes, Danielle H. Rochlin, Diana Call, Julie A. Freischlag
Journal: JAMA Surgery (2014)

Patients with neurogenic thoracic outlet syndrome (NTOS) may have signs and symptoms of arterial compromise without thrombosis or aneurysm.To evaluate these patients' presentation, duration of signs and symptoms, and outcomes of immediate surgical operation.Demographic and clinical data for patients with NTOS and signs and symptoms of arterial compromise without arterial thrombosis or aneurysm were extracted from a prospectively maintained, institutional review board-approved database and patient medical records between May 22, 2003, and October 16, 2012, in the Johns Hopkins Medical Institutions' Department of Vascular and Endovascular Surgery.All patients received immediate first rib resection and scalenectomy (FRRS) (n = 15), cervical rib resection and FRRS (n = 6), or FRRS and second rib resection due to fusion (n = 1). Further physical therapy or anterior scalene block was not considered owing to arterial compression.Surgical intervention relieved arterial and neurogenic symptoms, and abnormal duplex velocities returned to normal in adduction.Twenty-two patients (13 women and 9 men; mean age, 25 years [range, 12-41 years]) presented with the following signs and symptoms a mean of 37 months (range, 1-144 months) after developing symptoms of NTOS: arm discoloration (n = 15), infraclavicular bruit with arm abduction (n = 9), more than 50% change in subclavian artery velocity in abduction by duplex scan (n = 12), cervical rib (n = 6), abnormal first rib (n = 3), and/or history of embolization (n = 2). In addition, 2 patients had venous thrombosis. The mean follow-up time was 11 months (range, 1-34 months), and all patient outcomes improved in the postoperative period.Arterial compression can coexist with NTOS and can be elucidated in most patients by medical record review and physical examination, along with confirmation by a duplex scan. Those with evidence of arterial compression and for whom physical therapy has failed should receive surgery to alleviate their symptoms. Prompt surgical intervention affords good outcomes in these patients. Outcomes for patients with NTOS and arterial compression following immediate surgical intervention were previously unknown.
Airborne fungi in the homes of children with asthma in low-income urban communities: The Inner-City Asthma Study
Authors: George T. O'Connor, Michelle Walter, Herman Mitchell, Meyer Kattan, Wayne J. Morgan, Rebecca S. Gruchalla, Jacqueline A. Pongracic, Ernestine Smartt, James W. Stout, Richard Evans III
Journal: Journal of Allergy and Clinical Immunology (2004)
Keyhole biopsy: an easy and better alternative to fine-needle aspiration or Tru-cut biopsy of submucosal gastrointestinal tumors
Authors: P. Grubel
Journal: Endoscopy (2010)

I read with great interest the recent studies of Fernandez-Esparrach [1] and Philipper [2] on diagnosing gastrointestinal stromal tumors (GIST). I agree with their observations that endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is often hampered by the lack of sufficient tissue to allow histology and immunohistochemistry to be done and that Tru-cut biopsy is technically impossible when the endoscope is angulated.
Modulation of eIF5A Expression Using SNS01 Nanoparticles Inhibits NF-κB Activity and Tumor Growth in Murine Models of Multiple Myeloma
Authors: Catherine A Taylor, Zhongda Liu, Terence C Tang, Qifa Zheng, Sarah Francis, Tzann-Wei Wang, Bin Ye, John A Lust, Richard Dondero, John E Thompson
Journal: Molecular Therapy (2012)

Despite recent advances in the first-line treatment of multiple myeloma, almost all patients eventually experience relapse with drug-resistant disease. New therapeutic modalities are needed, and to this end, SNS01, a therapeutic nanoparticle, is being investigated for treatment of multiple myeloma. The antitumoral activity of SNS01 is based upon modulation of eukaryotic translation initiation factor 5A (eIF5A), a highly conserved protein that is involved in many cellular processes including proliferation, apoptosis, differentiation and inflammation. eIF5A is regulated by post-translational hypusine modification, and overexpression of hypusination-resistant mutants of eIF5A induces apoptosis in many types of cancer cells. SNS01 is a polyethylenimine (PEI)-based nanoparticle that contains both a B-cell-specific expression plasmid expressing a non-hypusinable mutant of eIF5A and a small interfering RNA (siRNA) which depletes endogenous hypusinated eIF5A. Reducing hypusine-modified eIF5A levels was found to inhibit phosphorylation and activity of ERK MAPK and nuclear factor-κB (NF-κB), and thus sensitize myeloma cells to apoptosis resulting from transfection of a plasmid expressing eIF5A(K50R). SNS01 exhibited significant antitumoral activity in both KAS-6/1 (95% inhibition; P < 0.05) and RPMI 8226 (59% inhibition; P < 0.05) multiple myeloma xenograft models following systemic administration. These results highlight the potential of using this approach as a new therapeutic strategy for multiple myeloma.
1.65 Copy number variation of<i>TLR7</i>and<i>TLR8</i>genes is age and sex biased: which role in autoimmunity?
Authors: Sami B Kanaan, Doua F Azzouz, Nathalie Balandraud, Christophe Picard, Isabelle Auger, Fanny Arnoux, Marielle Martin, Jean Roudier, Nathalie C Lambert
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Women, having two X chromosomes, are more predisposed than men to autoimmune diseases. The X chromosome contains many genes linked to immunity which may contribute to this gender bias. In a mouse model, a duplication of the innate immunity X-linked toll like receptor 7 (<i>Tlr7</i>) gene has been shown to potentiate autoimmunity in males. We then proposed to investigate whether <i>TLR7</i> gene and its neighboring paralog <i>TLR8</i> could have variations in their copy numbers, contributing to the pathogenesis of rheumatoid arthritis (RA) in men. <h3>Methods</h3> A real-time quantitative PCR protocol was developed to assess copy number variation (CNV) of <i>TLR7</i> and <i>TLR8</i> gene, using sensitive and optimised ΔΔCt and standard curve methods, in DNA from peripheral blood mononuclear cells of 60 patients with RA (including 49 men) and 64 healthy controls (including 42 men). Among them, 31 men with RA and 18 healthy men were further screened for <i>TLR7/8</i> CNV in 4 subpopulations: B cells, T cells, granulocytes and the depleted fraction of the former 3. <h3>Results</h3> <i> TLR7/8</i> copy numbers significantly increased with age in PBMCs from all men (<i>P</i> &lt; 0.0001, Spearman’s rank correlation test), whether they had RA or not. The increase had mean amplitude of 20%, spanning from the age of 20 until 80, according to the linear-regression-curve’s best fit. This age-dependent and disease-independent CNV increase was also observed in all cell subsets. Interestingly, such increase was not observed in women, healthy or with RA, but rather an opposite trend. <h3>Conclusion and Perspectives</h3> For the first time we showed an increased CNV in <i>TLR7</i> and <i>TLR8</i> genes which is age and sex-mediated. Several hypotheses could explain such phenomenon. For example, somatically acquired duplications can affect some cells over time and result in an increase with age in men. In parallel, X chromosome monosomy, previously described in aging women could account for the opposite trend in those. Another explanation for men can be due to the presence of feminine microchimerism, arising from feto-maternal or twin sister exchange during <i>in utero</i> life, as previously described. Such cells would carry 2 X chromosomes and contribute to the increased pool of X-linked genes among XY host cells. Investigating these hypotheses would provide better understanding of age-associated X-linked genetic modifications and the role of the X chromosome in gender differences in health and disease. Abstract topicOther
A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome
Authors: Nathalie Neyroud, Frédérique Tesson, Isabelle Denjoy, Michel Leibovici, Claire Donger, Jacques Barhanin, Sabine Fauré, Françoise Gary, Philippe Coumel, Christine Petit, Ketty Schwartz, Pascale Guicheney
Journal: Nature Genetics (1997)
NEUTRALIZING ANTIBODIES IN HUMAN SERUM AFTER INFLUENZA A
Authors: F. L. Horsfall, E. R. Rickard
Journal: The Journal of Experimental Medicine (1941)

The increased concentrations of neutralizing antibodies against influenza A virus in human serum which occur after influenza A do not differentiate between antigenically different strains of this virus or swine influenza virus but instead appear to possess equal reactivity against these agents. The decrease in antibody levels which occurs with time is also independent of the strain of virus used to measure it.