tbuckley/cabot-search huggingface dataset:
Natural killer (NK) cell response to virus infections in mice with severe combined immunodeficiency. The stimulation of NK cells and the NK cell-dependent control of virus infections occur independently of T and B cell function.
Authors: R M Welsh, J O Brubaker, M Vargas-Cortes, C L O'Donnell
Journal: The Journal of Experimental Medicine (1991)

The activation, proliferation, and antiviral properties of natural killer (NK) cells were examined in severe combined immunodeficiency (SCID) mice to determine the influence of mature T or B cells on virus-induced NK cell functions and to more conclusively determine the antiviral properties of prototypical CD3- NK cells. NK cells were activated to high levels of cytotoxicity 3 d after infection of mice with lymphocytic choriomeningitis virus (LCMV) or murine cytomegalovirus (MCMV). Analyses of spleen leukocytes from LCMV-infected mice by a variety of techniques indicated that the NK cells proliferated and increased in number during infection. Propidium iodide staining of the DNA of cycling cells revealed that the great majority of proliferating spleen leukocytes 3 d after LCMV infection was of the NK cell phenotype (CD3-, Ig-, Mac-1+, CZ1+, 50% Thy-1+), in contrast to uninfected mice, whose proliferating cells were predominantly of other lineages. Analyses of the NK cell responses over a 2 wk period in control CB17 mice infected with MCMV indicated a sharp rise in serum interferon (IFN) and spleen NK cell activity early (days 3-5) in infection, followed by sharp declines at later stages. In SCID mice the IFN levels continued to rise over a 10-d period, whereas the NK cell response peaked on day 3-5 and gradually tapered. In contrast to the immunocompetent CB17 mice, SCID mice did not clear the MCMV infection and eventually succumbed. SCID mice, again in contrast to immunocompetent CB17 mice, also failed to clear infections with LCMV and Pichinde virus (PV); these mice, infected as adults, did not die but instead developed long-term persistent infections. Depletion of the NK cells in vivo with antiserum to asialo GM1 rendered both SCID and CB17 control mice much more sensitive to MCMV infection, as shown by titers of virus in organs and by survival curves. In contrast, similar depletions of NK cells did not enhance the titers of the NK cell-resistant virus, LCMV. Two variants of PV, one sensitive to NK cells and the other selected for resistance to NK cells by in vivo passage, were also tested in NK cell-depleted SCID mice. The NK-sensitive PV replicated to higher titers in NK cell-depleted SCID mice, whereas the titers of the NK cell-resistant PV were the same, whether or not the mice had NK cells. These experiments support the concept that CD3- prototypical NK cells mediate resistance to NK cell-sensitive viruses via a mechanism independent of antiviral or "natural" antibody.(ABSTRACT TRUNCATED AT 400 WORDS)
Mind the sustainability gap
Authors: Joern Fischer, Adrian D. Manning, Will Steffen, Deborah B. Rose, Katherine Daniell, Adam Felton, Stephen Garnett, Ben Gilna, Rob Heinsohn, David B. Lindenmayer, Ben MacDonald, Frank Mills, Barry Newell, Julian Reid, Libby Robin, Kate Sherren, Alan Wade
Journal: Trends in Ecology & Evolution (2007)
A patient with biliary colic and intestinal obstruction
Authors: Bas W van der Spek, Miguel A Cuesta, Maarten A Jacobs
Journal: Gut (2010)

A 38-year-old Caucasian male patient was referred to our emergency department with typical biliary colic. Medical and family history were unremarkable. Physical examination revealed a non-feverish mildly ill patient, with normal bowel sounds. In addition a remarkably ‘freckled’ skin was found, especially on periorbital and perioral skin and buccal mucosa (figure 1). Apart from abnormal liver enzymes (bilirubin 1.35 mg/dl, gamma-glutamyltransferase 1049 IU/l and alanine aminotransferase 286 IU/l) laboratory tests were normal. Abdominal ultrasonography showed dilated intra- and extrahepatic bile ducts and cholecystolithiasis but no signs of choledocholithiasis. An endoscopic retrograde cholangiopancreatography was performed because of presumed choledocholithiasis, but common bile duct cannulation was unsuccessful because of a large polypoid mass at its insertion (figure 2). During endoscopy multiple smaller polyps were seen in duodenum and stomach. Following endoscopic retrograde cholangiopancreatography …
Biweekly paclitaxel plus gemcitabine in advanced breast cancer: phase II trial and predictive value of HER2 extracellular domain
Authors: R. Colomer, A. Llombart-Cussac, A. Lluch, A. Barnadas, B. Ojeda, V. Carañana, Y. Fernández, J. García-Conde, S. Alonso, S. Montero, J. Hornedo, V. Guillem
Journal: Annals of Oncology (2004)
William Joseph O'Sullivan
Authors: K. A. N. McWhinney
Journal: BMJ (2014)

Throughout his life, William Joseph O’Sullivan (“Bill”) had an unshakeable pride in and love of his homeland and, in particular, the county of Cork. He was one of four children, and his father was the local doctor in the village of Doneraile, which boasted the presence of three telephones—numbered one, two, and three—of which the doctor was three and the others the post office and the police, respectively. The outdoor life was the norm during his childhood, inculcating a love of animals, in particular horses, although all were included, to the point where a goat was permitted to share his bedroom. Bill’s intuitive understanding and enjoyment of animals led him …
Abdominal aortic aneurysms and autosomal dominant polycystic kidney disease.
Authors: R Torra, C Nicolau, C Badenas, C Brú, L Pérez, X Estivill, A Darnell
Journal: Journal of the American Society of Nephrology (1996)

Although cases of autosomal dominant polycystic kidney disease (ADPKD) associated with abdominal aortic aneurysm have been repeatedly reported in the literature, no systematic studies of the aortas of these patients have been performed. In the study presented here, a sonographic study of the abdominal aorta in 139 ADPKD patients and in 149 healthy family members was carried out. For both groups, an increase in aortic diameter related to age and sex, (being wider in men than women) was found. In ADPKD patients, neither a wider aortic diameter nor a higher prevalence of abdominal aortic aneurysms could be found in any age group. It was concluded that, although these patients are prone to develop aortic aneurysms because of hypertension and associated connective tissue disorders, the presence of abdominal aortic aneurysms should be questioned as a frequent feature of ADPKD.
Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs)
Authors: G. Palmieri, G. Merola, P. Federico, L. Petillo, M. Marino, M. Lalle, M. Milella, A. Ceribelli, L. Montella, C. Merola, S. Del Prete, M. Bergaglio, S. De Placido, G. Di Lorenzo
Journal: Annals of Oncology (2009)
A refined model of sleep and the time course of memory formation
Authors: Matthew P. Walker
Journal: Behavioral and Brain Sciences (2005)

Research in the neurosciences continues to provide evidence that sleep plays a role in the processes of learning and memory. There is less of a consensus, however, regarding the precise stages of memory development during which sleep is considered a requirement, simply favorable, or not important. This article begins with an overview of recent studies regarding sleep and learning, predominantly in the procedural memory domain, and is measured against our current understanding of the mechanisms that govern memory formation. Based on these considerations, I offer a new neurocognitive framework of procedural learning, consisting first of acquisition, followed by two specific stages of consolidation, one involving a process of stabilization, the other involving enhancement, whereby delayed learning occurs. Psychophysiological evidence indicates that initial acquisition does not rely fundamentally on sleep. This also appears to be true for the stabilization phase of consolidation, with durable representations, resistant to interference, clearly developing in a successful manner during time awake (or just time, per se). In contrast, the consolidation stage, resulting in additional/enhanced learning in the absence of further rehearsal, does appear to rely on the process of sleep, with evidence for specific sleep-stage dependencies across the procedural domain. Evaluations at a molecular, cellular, and systems level currently offer several sleep specific candidates that could play a role in sleep-dependent learning. These include the upregulation of select plasticity-associated genes, increased protein synthesis, changes in neurotransmitter concentration, and specific electrical events in neuronal networks that modulate synaptic potentiation.
BH3 Mimetic Obatoclax Enhances TRAIL-Mediated Apoptosis in Human Pancreatic Cancer Cells
Authors: Shengbing Huang, Kenji Okumura, Frank A. Sinicrope
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Prosurvival Bcl-2 proteins inhibit the mitochondrial and death receptor-mediated apoptotic pathways. Obatoclax is a small-molecule antagonist of the BH3-binding groove of Bcl-2 proteins that may enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity and efficacy. Experimental Design: Human pancreatic cancer cell lines were incubated with obatoclax and/or TRAIL and cell viability, Annexin V labeling, caspase cleavage, and cytochrome c release were measured. In drug-treated cell lines, protein-protein interactions were studied by immunoprecipitation. Bax/Bak activation was analyzed using conformation-specific antibodies. Lentiviral short hairpin RNA was used to knockdown Bim, Bid, and apoptosis-inducing factor (AIF) expression. Results: Obatoclax reduced the viability of PANC-1 and BxPC-3 cell lines and synergistically enhanced TRAIL-mediated cytotoxicity. Obatoclax enhanced TRAIL-mediated apoptosis, as shown by Annexin V labeling, which was accompanied by caspase activation (caspase-8, -9, and -3) and cleavage of Bid. Obatoclax potentiated TRAIL-mediated Bax/Bak activation and the release of mitochondrial cytochrome c, Smac, and AIF. Mechanisms underlying the apoptotic effect of obatoclax include displacement of Bak from its sequestration by Bcl-xL or Mcl-1 and release of Bim from Bcl-2 or Mcl-1. Bid knockdown by short hairpin RNA attenuated caspase cleavage and cytotoxicity of obatoclax plus TRAIL. Bim knockdown failed to inhibit the cytotoxic effect of obatoclax alone or combined with TRAIL yet attenuated TRAIL-mediated cytotoxicity. AIF knockdown attenuated cytotoxicity of the drug combination. Conclusions: Obatoclax potentiates TRAIL-mediated apoptosis by unsequestering Bak and Bim from Bcl-2/Bcl-xL or Mcl-1 proteins. This drug combination enhances Bid-mediated cross-talk between the mitochondrial and death receptor-mediated apoptotic pathways and may represent a novel therapeutic strategy against pancreatic cancer.
Genetic control of the immune response to staphylococcal nuclease. III. Time-course and correlation between the response to native nuclease and the response to its polypeptide fragments.
Authors: J A Berzofsky, A N Schechter, G M Shearer, D H Sachs
Journal: The Journal of Experimental Medicine (1977)

The progression of the Ir gene-controlled antibody response to staphylococcal nuclease in mice with repeated immunizations has been examined. H-2-linked control of the response to a single immunization with 100 mug of nuclease in complete Freund's adjuvant was confirmed. However, among strains of the high responder H-2a haplotype, the response of the A/J mice was about 10-fold higher than that of the B10.A, indicating additional non-H-2-linked control. In addition, the low responder C57BL/10 (H-2b) strain produced antibody levels as high as or higher than those of the congenic high responder B10.A (H-2a) strain when both strains were repeatedly immunized, indicating complexity even in the H-2-linked control of the response to this small monomeric protein. Polypeptide fragments of nuclease were also studied as immunogens. The antibody response to one fragment (residues 99-149) was found to follow the same pattern among five strains tested as that to whole nuclease. However, in this case the C57BL/10 was found to be a nonresponder rather than a low responder, failing to develop a response despite repeated immunizations. In contrast, the C57BL/10 showed a low but significant response to another fragment (residues 1-126) of nuclease. These results suggest that the apparent H-2-linked control of the response to whole nuclease is a reflection of the ability to recognize a determinant(s) in the region from residues 99 to 149, and that the eventual response of the C57BL/10 strain after hyperimmunization reflects the recognition of other determinants. If these observations reflect the common recognition of a determinant on native nuclease and on a random-conformation fragment, they have implications about the conformational specificity of the receptors, or the flexibility of the determinants, involved in H-2-linked Ir-gene control. In addition, evidence is presented for a possible second H-2-linked gene (or genes) controlling the response to other determinants of nuclease expressed on the polypeptide fragments.
Antiphospholipid antibodies and rheumatoid arthritis
Authors: A Ambrozic
Journal: Annals of the Rheumatic Diseases (2002)

We read with interest the letter entitled “Antiphospholipid antibodies and RA: presence of β2GP1 independent aCL” by Bonnet et al published in the Annals in March 2001.1 We believe that the letter needs additional clarification owing to inconsistencies in the terminology, methodology of antiphospholipid antibody (aPL) detection, and determination of positive values.

The use of the term “anticardiolipin antibodies” was somewhat misleading. The term was introduced and abbreviated as “aCL”, a group of antibodies detected in many conditions, but the β2 glycoprotein 1 (β2GP1) dependence of the aCL was not defined, even though the authors focused on β2GP1 independent aCL. It is generally agreed that the term aCL, if not stated otherwise, defines the antibodies detected by the classical aCL enzyme linked immunosorbent assay (ELISA),2,3—that is, both β2GP1 dependent and β2GP1 independent antibodies.

There were some potential methodological errors in determining β2GP1 independent aCL. It was shown that antibodies against β2GP1 (anti-β2GP1) from patients with the antiphospholipid syndrome (APS) have the ability to bind β2GP1 in complexes with cardiolipin only if the β2GP1 concentration in solution is high enough. The threshold concentration of β2GP1 was found to be just about 2 μg/ml, because no binding of anti-β2GP1 was seen when serum samples were diluted 1:200 or more.4 As the physiological concentration of β2GP1 in human serum is approximately 200 μg/ml, the threshold binding concentration is reached at a serum dilution of 1:100. In the presence of a relatively high concentration of endogenous β2GP1, the statement that antibodies detected by this method are exclusively β2GP1 independent is unjustified, as the sera containing high titres of …
Geographic distribution of hematopoietic cancers in the Nile delta of Egypt
Authors: C.M. Herzog, S. Dey, A. Hablas, H.M. Khaled, I.A. Seifeldin, M. Ramadan, H. El-Hamzawy, M.L. Wilson, A.S. Soliman
Journal: Annals of Oncology (2012)
In Vitro Bactericidal Capacity of Human Polymorphonuclear Leukocytes: Diminished Activity in Chronic Granulomatous Disease of Childhood *
Authors: P. G. Quie, J. G. White, B. Holmes, R. A. Good
Journal: Journal of Clinical Investigation (1967)

Diminished bactericidal capacity was found to be characteristic of polymorphonuclear leukocytes (PMN) from five children with the clinical syndrome of granulomatous disease of childhood. The PMN from these children demonstrated nearly normal phagocytic capacity, and the majority of viable bacteria, after 2 hours of incubation in the phagocytosis system, were found associated with leukocytes. The morphology of the unstimulated polymorphonuclear leukocytes from patients with chronic granulomatous disease was similar to those from normal persons of similar ages by light and electron microscopy. In addition, the total lysozyme and phagocytin activity of leukocyte extracts from these patients was similar to those from equal numbers of leukocytes from controls.A striking difference in the cytoplasmic response after phagocytosis characterized the PMN of the patients with granulomatous disease. Whereas degranulation, vacuole formation, and rapid bacterial digestion were the rule in the PMN from controls, little degranulation and persistence of intact bacteria in the cytoplasm characterized disease. The deficiency of bactericidal capacity and the minimal degranulation after active phagocytosis by the PMN of these children with an inherited syndrome suggest that separate metabolic processes are involved in phagocytosis and in intracellular digestion. Continuing study of the metabolic function of leukocytes from these children should provide an opportunity for increased understanding of the metabolic basis for degranulation and intracellular digestion in phagocytic cells.
New Meets Old: A Case Study and Review of Novel Therapeutics for the Treatment of CLL in Older Patients
Authors: Neel K. Gupta, Charalambos Andreadis
Journal: Journal of the National Comprehensive Cancer Network (2014)

The treatment of older or medically frail patients with chronic lymphocytic leukemia (CLL) presents unique challenges to clinicians attempting to maximize efficacy while avoiding significant toxicity. This case report presents a 75-year-old man with Rai stage II CLL complicated by massive splenomegaly, high-risk cytogenetics, and intolerance to first-line therapy recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin's Lymphomas. A brief summary of his disease and treatment course accompanies a discussion of the special challenges associated with treating this patient population. In addition, emerging novel and targeted therapies, including next-generation monoclonal antibodies and small molecule inhibitors, are reviewed in the broader context of evolving standards of care and the NCCN Guidelines.
Remodeling and Neointimal Formation in the Carotid Artery of Normal and P-Selectin–Deficient Mice
Authors: Anjali Kumar, Jennifer L. Hoover, Carol A. Simmons, Volkhard Lindner, Ronald J. Shebuski
Journal: Circulation (1997)

Inflammatory reactions such as leukocyte activation with platelet adherence and release of inflammatory mediators occur after percutaneous transluminal coronary angioplasty and may play a role in restenosis. Vascular remodeling with neointimal formation was studied in normal C57Bl/J6 and P-selectin-deficient mice.The left common carotid artery was ligated just proximal to the carotid bifurcation. Four weeks later, left carotids and contralateral controls were snap-frozen. Computer-aided morphometry was performed to measure ratios of neointimal to medial area (NI/M) in 10 sections per animal as a measure of the thickness of the neointimal lesion. For normal mice, NI/M was 1.13+/-0.2 (n=20), whereas NI/M was reduced by 76% to 0.27+/-0.1 (n= 19) in P-selectin knockout mice. Vascular constriction (as measured by the length of external elastic lamina) was the same in both groups, but the circumference of the lumen in knockout mice was 26% larger. Also, normal and P-selectin-deficient mice were killed at 3 and 7 days after ligation (n=6 for each group per time point). Histological staining and immunostaining for CD45 showed no inflammatory cell presence in P-selectin knockout mice. However, in normal mice, leukocyte infiltration was observed in the adventitia, media, and developing neointima. Also, P-selectin immunostaining was observed in media and developing neointima of normal mice.These data suggest that P-selectin is involved in processes leading to cell migration and proliferation associated with vascular remodeling, presumably by mediating leukocyte recruitment and the interaction between platelets and leukocytes.
Relation between transcardiac and transthoracic current during defibrillation in humans.
Authors: B B Lerman, O C Deale
Journal: Circulation Research (1990)

Conceptually, transthoracic defibrillation threshold current can be considered a function of at least two quantities. It is directly proportional to the transcardiac threshold current and inversely proportional to the transcardiac current fraction (FC) or the ratio of transcardiac and transthoracic current. Although experimental and theoretical estimates of FC have been as high as 45%, previous measurements in humans have not been made. This study was designed to quantify FC in humans. During intraoperative testing of the automatic implantable cardioverter defibrillator, transthoracic rescue shocks of 200-400 J were delivered when the device failed to defibrillate. Simultaneous transthoracic voltage (VT) and transcardiac voltage (VC) between two implanted epicardial patch electrodes were measured. The ratio, VC/VT, was 0.04 +/- 0.03 (mean +/- SD) in 10 patients. In 16 dogs, a comparison was made between direct measurement of FC and VC/VT. FC was determined with a specially designed electrode system, which was calibrated to account for field distortion introduced by the electrodes. There was no significant difference between FC and VC/VT, which were both approximately 0.05, suggesting that VC/VT was statistically equivalent to FC. The results of this study, therefore, indicate that during transthoracic defibrillation in humans, approximately 4% of transthoracic current traverses the heart. This relatively small percentage of current results from the existence of parallel pathways, such as the thoracic cage and lungs, which shunt current around the heart.
Body Iron Stores and Risk of Colonic Neoplasia
Authors: R. L. Nelson, F. G. Davis, E. Sutter, L. H. Sobin, J. W. Kikendall, P. Bowen
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Body Iron Stores and Risk of Colonic Neoplasia Get access Richard L. Nelson, Richard L. Nelson Epidemiology and Biostatistics Division, School of Publis Health, University of Illinoisat Chicago Search for other works by this author on: Oxford Academic PubMed Google Scholar Faith G. Davis, Faith G. Davis Epidemiology and Biostatistics Division, School of Publis Health, University of Illinoisat Chicago Search for other works by this author on: Oxford Academic PubMed Google Scholar Eileen Sutter, Eileen Sutter Epidemiology and Biostatistics Division, School of Publis Health, University of Illinoisat Chicago Search for other works by this author on: Oxford Academic PubMed Google Scholar Leslie H. Sobin, Leslie H. Sobin Division of Gastrointestinal Pathology, Armed Forces Institute of PathologyWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Walter Kikendall, J. Walter Kikendall Gastroenterology Service, Walter Reed Army Medical CenterWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Phyllis Bowen Phyllis Bowen * Department of Nutrition and Medical Dietetics, College of Associated Health Professions, University of Illinoisat Chicago * Correspondence to: Richard L. Nelson. M.D., Department of Surgery. University of Illinois College of Medicine at Chicago, 1740 West Taylor St., Rm. 2204, M/C 957. Chicago. IL 60612. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 6, 16 March 1994, Pages 455–460, https://doi.org/10.1093/jnci/86.6.455 Published: 16 March 1994 Article history Received: 13 September 1993 Revision received: 21 December 1993 Accepted: 05 January 1994 Published: 16 March 1994