tbuckley/cabot-search huggingface dataset:
Migratory behavior of lymphocytes with specific reactivity to alloantigens. II. Selective recruitment to lymphoid cell allografts and their draining lymph nodes.
Authors: E E Emeson
Journal: The Journal of Experimental Medicine (1978)

A dual-antigen, dual-isotope assay has been used to monitor the migratory behavior of selectively labeled antiallogeneic lymphocytes in mice challenged subcutaneously in all four foot pads with semiallogeneic spleen cells. 3H-labeled anti-C3H and 14C-labeled anti-C57BL lymphocytes of DBA/2J origin were pooled and adoptively transferred to multiple groups of previously challenged DBA/2J recipients. In some of the studies, separate groups of recipients were challenged with either CDF or BDF spleen cells in all four paws, whereas in others CDF spleen cells were used to challenge the right paws of each mouse in the group and BDF spleen cells to challenge the left paws of each mouse in the group. At intervals varying from 24 to 96 h after challenge, a subgroup of four mice from each appropriate group was sacrificed and the relative numbers of anti-C3H and anti-C57BL lymphocytes present in the challenged paws, draining lymph nodes, and other tissues of each mouse were inferred from the mean 3H/14C ratios of the respective tissues of that subgroup. The results of these studies firmly establish that specific antiallogeneic lymphocytes are selectively recruited to the paws and draining lymph nodes of mice challenged subcutaneously in the foot pads with semiallogeneic spleen cells and are deleted from their circulating blood and nondraining lymph nodes. A mechanism for antigen-induced selective recruitment and its possible functional significance in tumor immunology are discussed.
Motile sperm organelle morphology examination (MSOME) and sperm head vacuoles: state of the art in 2013
Authors: Anne Perdrix, Nathalie Rives
Journal: Human Reproduction Update (2013)

BACKGROUND Approximately 10 years after the first publication introducing the motile sperm organelle morphology examination (MSOME), many questions remained about sperm vacuoles: frequency, size, localization, mode of occurrence, biological significance and impact on male fertility potential. Many studies have tried to characterize sperm vacuoles, to determine the sperm abnormalities possibly associated with vacuoles, to test the diagnostic value of MSOME for male infertility or to question the benefits of intracytoplasmic morphologically selected sperm injection (IMSI). METHODS We searched PubMed for articles in the English language published in 2001-2012 regarding human sperm head vacuoles, MSOME and IMSI. RESULTS A bibliographic analysis revealed consensus for the following findings: (i) sperm vacuoles appeared frequently, often multiple and preferentially anterior; (ii) sperm vacuoles and sperm chromatin immaturity have been associated, particularly in the case of large vacuoles; (iii) teratozoospermia was a preferred indication of MSOME and IMSI. CONCLUSION The high-magnification system appears to be a powerful method to improve our understanding of human spermatozoa. However, its clinical use remains unclear in the fields of male infertility diagnosis and assisted reproduction techniques (ARTs).
Use of a Combination of Anion and Cation Exchange Resins in the Treatment of Edema and Ascites
Authors: B. L. MARTZ, K. G. KOHLSTAEDT, O. M. HELMER
Journal: Circulation (1952)

A mixture of a carboxylic acid type of cation exchange resin and a weakly basic anion exchange resin has been used successfully to control the edema of 42 patients with congestive heart failure and the ascites of 14 patients with cirrhosis of the liver. Approximately one-third of the cation exchanger was supplied in the potassium cycle. Inclusion of the anion exchange resin resulted in a greater sodium uptake per gram of resin and apparently decreased the incidence of disturbances in acid-base balance in patients with impaired renal function who were treated with resins.
Immune correlates of vaccine protection against HIV-1 acquisition
Authors: Lawrence Corey, Peter B. Gilbert, Georgia D. Tomaras, Barton F. Haynes, Giuseppe Pantaleo, Anthony S. Fauci
Journal: Science Translational Medicine (2015)

The partial efficacy reported in the RV144 HIV vaccine trial in 2009 has driven the HIV vaccine field to define correlates of risk associated with HIV-1 acquisition and connect these functionally to preventing HIV infection. Immunological correlates, mainly including CD4(+) T cell responses to the HIV envelope and Fc-mediated antibody effector function, have been connected to reduced acquisition. These immunological correlates place immunological and genetic pressure on the virus. Indeed, antibodies directed at conserved regions of the V1V2 loop and antibodies that mediate antibody-dependent cellular cytotoxicity to HIV envelope in the absence of inhibiting serum immunoglobulin A antibodies correlated with decreased HIV risk. More recently, researchers have expanded their search with nonhuman primate studies using vaccine regimens that differ from that used in RV144; these studies indicate that non-neutralizing antibodies are associated with protection from experimental lentivirus challenge as well. These immunological correlates have provided the basis for the design of a next generation of vaccine regimens to improve upon the qualitative and quantitative degree of magnitude of these immune responses on HIV acquisition.
Endothelial Cell Activation in Patients With Decompensated Heart Failure
Authors: Paolo C. Colombo, Javier E. Banchs, Sulejman Celaj, Ashok Talreja, Justine Lachmann, Shailesh Malla, Nicholas B. DuBois, Anthony W. Ashton, Farhana Latif, Ulrich P. Jorde, J. Anthony Ware, Thierry H. LeJemtel
Journal: Circulation (2004)

Vascular endothelial functions, other than nitric oxide (NO)-mediated control of vasomotor tone, are poorly characterized in patients with chronic heart failure (CHF). Veins and arteries are exposed to the same circulating proinflammatory mediators in patients with CHF. The present study tested whether endothelial cell activation occurs in veins of patients with decompensated CHF and whether activation, if present, subsides with return to a clinically compensated state.Fifteen patients with decompensated CHF requiring transient inotropic support and 6 age-matched, healthy controls were studied. Endothelial cells and blood were collected from a forearm vein, and brachial artery flow-mediated dilation (FMD) was measured before and 24 hours after discontinuation of short-term inotropic therapy, when patients had returned to a steady compensated state. Nitrotyrosine immunoreactivity (an intracellular marker of oxidative stress), cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS) expression were significantly higher in venous endothelial cells of patients in clinical decompensation when compared with healthy subjects. Return to a compensated state resulted in a significant reduction in nitrotyrosine immunoreactivity, COX-2, and iNOS expression. Concomitantly, a significant increase in FMD and a decline in plasma total 8-isoprostane and bicycloprostaglandin E2 levels were observed. Venous endothelial NOS expression was unaffected by clinical decompensation.Clinical decompensation in CHF is associated with activation of the venous endothelium. Return to a compensated state after short-term inotropic therapy results in a significant reduction in endothelial nitrotyrosine formation, COX-2, and iNOS expression.
Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial
Authors: Adam L Boxer, David S Knopman, Daniel I Kaufer, Murray Grossman, Chiadi Onyike, Neill Graf-Radford, Mario Mendez, Diana Kerwin, Alan Lerner, Chuang-Kuo Wu, Mary Koestler, Jill Shapira, Kathryn Sullivan, Kristen Klepac, Kristine Lipowski, Jerin Ullah, Scott Fields, Joel H Kramer, Jennifer Merrilees, John Neuhaus, M Marsel Mesulam, Bruce L Miller
Journal: The Lancet Neurology (2013)
Unplanned and assisted conception pregnancies
Authors: J. D. Gipson, J. S. Santelli
Journal: BMJ (2011)

High prevalence of unplanned pregnancy warrants primary and secondary prevention efforts

Among the most important decisions that individuals and couples face during their reproductive years is if and when to have a child, and how many children to have. Ideally, pregnancy occurs if and when it is desired. However, reproductive outcomes commonly occur that are contrary to plans and desires. Infertility affects 15-25% of couples worldwide, while four of every 10 pregnancies that occur globally are considered to be unintended.1 2

In the linked study (doi:10.1136/bmj.d4473), Carson and colleagues assess cognitive abilities (verbal, non-verbal, and spatial) in children of women who considered their pregnancies to be unplanned, mistimed, and planned, as well as women who were subfertile, needed ovulation induction, or had assisted reproductive technology.3 

Many studies have linked unintended pregnancies with negative health and social outcomes for mothers and children, including delayed and insufficient antenatal care, lower likelihood and shorter duration of breast feeding, and higher rates of depression and anxiety among mothers.4 …
THE MOVEMENT OF WATER IN TUMOR TISSUE REMOVED FROM THE BODY
Authors: Eugene L. Opie
Journal: The Journal of Experimental Medicine (1949)

When immersed in water cells of hepatomas produced by p-dimethyl-aminoazobenzene (butter yellow) take in less water than liver cells from which they are derived and more rapidly undergo disintegration; cholangiomas produced by butter yellow undergo similar changes. As a result of the injury of the tumor cells by water the osmotic exchange, characteristic of the normal liver cells under the same conditions, is impaired within the initial half hour of immersion. Solutions of sodium chloride isotonic for hepatoma tissue have a concentration approximating 0.16 molar and for cholangioma, 0.2 molar, whereas solutions isotonic for normal liver tissue approximate 0.34 molar. Water exchange of hepatoma and of cholangioma tissue in solutions of sodium chloride of various concentrations deviates from a proportional relation to the concentration more than does normal liver tissue under the same conditions. Water exchange of sarcoma of the subcutaneous tissue produced by benzpyrene when immersed in water resembles that of interstitial fibrous tissue of normal animals, but by the procedures that have been used water exchange of the tumor cells alone has not been measurable. Microscopic examination indicates that the sarcoma cells are as susceptible to injury as those of the other tumors that have been examined. Intake of water by adenofibromas of the subcutaneous tissue is apparently dominated by changes in the dense stroma of the tumor and has the anomalous character of intake bycompact fibrous tissue of the corium of the skin and of the wall of the aorta.
PLZF induces an intravascular surveillance program mediated by long-lived LFA-1–ICAM-1 interactions
Authors: Seddon Y. Thomas, Seth T. Scanlon, Klaus G. Griewank, Michael G. Constantinides, Adam K. Savage, Kenneth A. Barr, Fanyong Meng, Andrew D. Luster, Albert Bendelac
Journal: The Journal of Experimental Medicine (2011)

Innate-like NKT cells conspicuously accumulate within the liver microvasculature of healthy mice, crawling on the luminal side of endothelial cells, but their general recirculation pattern and the mechanism of their intravascular behavior have not been elucidated. Using parabiotic mice, we demonstrated that, despite their intravascular location, most liver NKT cells failed to recirculate. Antibody blocking experiments established that they were retained locally through constitutive LFA-1–intercellular adhesion molecule (ICAM) 1 interactions. This unprecedented lifelong intravascular residence could be induced in conventional CD4 T cells by the sole expression of promyelocytic leukemia zinc finger (PLZF), a transcription factor specifically expressed in the NKT lineage. These findings reveal the unique genetic and biochemical pathway that underlies the innate intravascular surveillance program of NKT cells.
Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort
Authors: R K Weersma, P C F Stokkers, A A van Bodegraven, R A van Hogezand, H W Verspaget, D J de Jong, C J van der Woude, B Oldenburg, R K Linskens, E A M Festen, G van der Steege, D W Hommes, J B A Crusius, C Wijmenga, I M Nolte, G Dijkstra
Journal: Gut (2008)

<h3>Background:</h3> Crohn’s disease and ulcerative colitis have a complex genetic background. We assessed the risk for both the development and severity of the disease by combining information from genetic variants associated with inflammatory bowel disease (IBD). <h3>Methods:</h3> We studied 2804 patients (1684 with Crohn’s disease and 1120 with ulcerative colitis) and 1350 controls from seven university hospitals. Details of the phenotype were available for 1600 patients with Crohn’s disease and for 800 with ulcerative colitis. Genetic association for disease susceptibility was tested for the nucleotide-binding and oligomerisation domain 2 gene (<i>NOD2</i>), the IBD5 locus, the Drosophila discs large homologue 5 and autophagy-related 16-like 1 genes (<i>DLG5</i> and <i>ATG16L1</i>) and the interleukin 23 receptor gene (<i>IL23R</i>). Interaction analysis was performed for Crohn’s disease using the most associated single nucleotide polymorphism (SNP) for each locus. Odds ratios were calculated in an ordinal regression analysis with the number of risk alleles as an independent variable to analyse disease development and severity. <h3>Results:</h3> Association with Crohn’s disease was confirmed for <i>NOD2</i>, IBD5, <i>DLG5</i>, <i>ATG16L1</i> and <i>IL23R</i>. Patients with Crohn’s disease carry more risk alleles than controls (p = 3.85 × 10<sup>−22</sup>). Individuals carrying an increasing number of risk alleles have an increasing risk for Crohn’s disease, consistent with an independent effects multiplicative model (trend analysis p = 4.25 × 10<sup>−23</sup>). Patients with Crohn’s disease with a more severe disease course, operations or an age of onset below 40 years have more risk alleles compared to non-stricturing, non-penetrating behaviour (p = 0.0008), no operations (p = 0.02) or age of onset above 40 years (p = 0.028). <h3>Conclusion:</h3> Crohn’s disease is a multigenic disorder. An increase in the number of risk alleles is associated with an increased risk for the development of Crohn’s disease and with a more severe disease course. Combining information from the known common risk polymorphisms may enable clinicians to predict the course of Crohn’s disease.
Gastrointestinal and Liver Disease, 7th Edn Online. Pathophysiology/Diagnosis/Management
Authors: D A van Heel
Journal: Gut (2004)

Edited by M Feldman, L S Friedman, M H Sleisenger. Amsterdam: Elsevier, £65.99. ISBN 0 7216 8973 6

The mighty Sleisenger and Fordtran textbook now comes in three varieties: two volume hardback, online only access, or both. “Evolving at the speed of medicine” sounded pretty good but would the internet version be any use for me? All three of the hospitals I currently work at now have easy computer access at the clinic desk and on the wards, so it seemed an appealing prospect to carry around just a password rather than seven kilos of weighty tome.

The 7th edition online is exactly as …
Identification of human erythrocyte blood group antigens on decay- accelerating factor (DAF) and an erythrocyte phenotype negative for daf
Authors: MJ Telen, SE Hall, AM Green, None Moulds, None Rosse
Journal: The Journal of Experimental Medicine (1988)

Decay accelerating factor (DAF) is a glycoprotein present on the surfaces of many types ofcells in contact with plasma, including erythrocytes, leukocytes, and platelets (reviewed in reference 1). A small amount of DAF is also present in serum. Numerous investigators have demonstrated that DAF inhibits the action of C3 convertases on cell surfaces, and its absence has been shown to be at least partially responsible for the abnormal sensitivity to lysis by complement exhibited by erythrocytes of patients with the acquired stem cell disorder paroxysmal nocturnal hemoglobinuria (PNH) (2). Hereditary absence of DAF has not been previously described. Tc(a) and Cr(a) are high-frequency human erythrocyte antigens . These antigens are part of a family of blood group antigens, designated Cromer related, which are all absent from the null phenotype cell IFC(-) , or Inab (3). Recently, Spring and colleagues (4) have identified two monoclonal antibodies which bound to high frequency red cell antigens absent from the Inab phenotype. They also demonstrated that these antibodies, as well as several human antisera to Cromer-related antigens, bound to a 70-kD glycoprotein when used to stain immunoblots of human erythrocyte membrane proteins . Because the wide tissue distribution of mAb reactivity, along with some of the biochemical characterization and immunoblotting data, was similar to that of DAF, we investigated whether the Cromer-related antigens Cr(a) and Tc(a) resided on the DAF molecule.
Structural requirements regulate endoproteolytic release of the L-selectin (CD62L) adhesion receptor from the cell surface of leukocytes.
Authors: A Chen, P Engel, T F Tedder
Journal: The Journal of Experimental Medicine (1995)

L-selectin mediates leukocyte rolling on vascular endothelium at sites of inflammation and lymphocyte migration to peripheral lymph nodes. L-selectin is rapidly shed from the cell surface after leukocyte activation by a proteolytic mechanism that cleaves the receptor in a membrane proximal extracellular region. This process may allow rapid leukocyte detachment from the endothelial surface before entry into tissues. In this study, the structural requirements for regulation of human L-selectin endoproteolytic release were examined through analysis of chimeric selectin molecules and mutant L-selectin receptors. The use of chimeric selectins and a cytoplasmic tail truncation mutant demonstrated that the extracellular membrane-proximal 15-amino acid region of L-selectin is required for endoproteolytic release. The introduction of alanine-scanning mutations within this membrane-proximal region did not prevent endoproteolytic release, indicating that a specific amino acid motif was not an absolute requirement for cleavage. Furthermore, alterations within the putative primary cleavage site (K283-S284) resulted in either constitutive endoproteolytic release of the receptor or inhibition of cell activation-induced shedding to variable extents. The length of the membrane-proximal region was also critical since truncations of this region completely abolished endoproteolytic release. Thus, release of L-selectin is likely to be regulated by the generation of an appropriate tertiary conformation within the membrane-proximal region of the receptor which allows recognition by a membrane-bound endoprotease with relaxed sequence specificity that cleaves the receptor at a specific distance from the plasma membrane. These observations suggest a generalized protein-processing pathway involved in the endoproteolytic release of specific transmembrane proteins which harbor widely differing primary sequences at or neighboring their cleavage sites.
Severe soccer injuries in amateurs
Authors: I E Goga, P Gongal
Journal: British Journal of Sports Medicine (2003)

To ascertain the number and type of severe soccer injuries admitted to King Edward Hospital in South Africa over 42 months.This was a retrospective study of all patients admitted for treatment or observation to the orthopaedic unit only. Patients treated as outpatients, irrespective of severity, are also presented for comparison.Thirty two patients were admitted with severe injuries. The injuries included 18 fractures of the tibial and femoral shaft. Two tibial shaft fractures were compound. Four tibial plateau fractures and five epiphyseal injuries were identified. One patient had a fracture-dislocation of the hip. One patient with a popliteal artery injury presented 48 hours after the injury had occurred. He had an above knee amputation. In the same period 122 patients were treated as outpatients. The types of injury in this group were similar to soccer injuries reported in other countries.Very serious injuries are sustained by casual soccer players in South Africa. Urgent measures need to be taken to prevent such injuries.
Overlapping T cell antigenic sites on a synthetic peptide fragment from herpes simplex virus glycoprotein D, the degenerate MHC restriction elicited, and functional evidence for antigen-Ia interaction.
Authors: E Heber-Katz, S Valentine, B Dietzschold, C Burns-Purzycki
Journal: The Journal of Experimental Medicine (1988)

Analysis of the B10.A T cell response to synthetic peptides representing the NH2-terminal 23 amino acids from the HSV glycoprotein D sequence revealed two antigenic determinants for T cells: one localized between residues 1-16 and the other between residues 8-23. The 1-16 site, which is helical, was recognized in the context of the Ia molecule, whereas the 8-23 site, which is nonhelical, was recognized in the context of the I-E molecule. The I-E-restricted response was found to be highly MHC degenerate in that T cell hybridomas specific for the 8-23 peptide responded to antigen on APCs derived from B10.A, B10.A(5R), and B10.A(9R) mice and showed differences in antigenic fine specificity with APCs of different haplotypes. These data support the idea of antigen-Ia interaction.
Merkel Polyomavirus-Specific T Cells Fluctuate with Merkel Cell Carcinoma Burden and Express Therapeutically Targetable PD-1 and Tim-3 Exhaustion Markers
Authors: Olga K. Afanasiev, Lola Yelistratova, Natalie Miller, Kotaro Nagase, Kelly Paulson, Jayasri G. Iyer, Dafina Ibrani, David M. Koelle, Paul Nghiem
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The persistent expression of Merkel cell polyomavirus (MCPyV) oncoproteins in Merkel cell carcinoma (MCC) provides a unique opportunity to characterize immune evasion mechanisms in human cancer. We isolated MCPyV-specific T cells and determined their frequency and functional status. Experimental Design: Multiparameter flow cytometry panels and HLA/peptide tetramers were used to identify and characterize T cells from tumors (n = 7) and blood (n = 18) of patients with MCC and control subjects (n = 10). PD-1 ligand (PD-L1) and CD8 expression within tumors were determined using mRNA profiling (n = 35) and immunohistochemistry (n = 13). Results: MCPyV-specific CD8 T cells were detected directly ex vivo from the blood samples of 7 out of 11 (64%) patients with MCPyV-positive tumors. In contrast, 0 of 10 control subjects had detectable levels of these cells in their blood (P &amp;lt; 0.01). MCPyV-specific T cells in serial blood specimens increased with MCC disease progression and decreased with effective therapy. MCPyV-specific CD8 T cells and MCC-infiltrating lymphocytes expressed higher levels of therapeutically targetable PD-1 and Tim-3 inhibitory receptors compared with T cells specific to other human viruses (P &amp;lt; 0.01). PD-L1 was present in 9 of 13 (69%) MCCs and its expression was correlated with CD8-lymphocyte infiltration. Conclusions: MCC-targeting T cells expand with tumor burden and express high levels of immune checkpoint receptors PD-1 and Tim-3. Reversal of these inhibitory pathways is therefore a promising therapeutic approach for this virus-driven cancer. Clin Cancer Res; 19(19); 5351–60. ©2013 AACR.