tbuckley/cabot-search huggingface dataset:
Henry Jeffray Weston
Authors: R. H. R. White
Journal: BMJ (2010)

Henry Jeffray Weston—known by family, friends, and colleagues as “Jeff”—was born on 9 September 1926 in New Plymouth, New Zealand, where his father was a newspaper proprietor. He studied medicine at the University of Otago Medical School, completing his final clinical year at Wellington Hospital, and graduating MB ChB in 1950. Following junior appointments at Wellington Hospital, he came to London in 1955, where he held house physician posts at the Hammersmith and Brompton Hospitals—traditional training grounds for Commonwealth postgraduates—leading to the MRCP (London), which was essential at that time for paediatric trainees.

He had already set his sights on a career in paediatrics, and in 1956 obtained posts as house physician, then registrar, in the cardiorespiratory unit at Great Ormond Street, where I first met him. After two more years as resident assistant physician (RAP), he returned to New Zealand, and was appointed consultant paediatrician to Wellington …
Colour Atlas of Paediatric Haematology
Authors: Ruth Andrea Seeler
Journal: JAMA (1984)

Why an atlas of pediatric hematology in 1983? Hasn't the field become a study in biochemistry and molecular genetics? True, but many of these biochemical abnormalities still produce morphological change, and this is where the clinician has to start! On reflection, I realized that when questioned by house officers and students, I turned to the larger texts or to the reprint file or my personal slide collection to provide appropriate illustrations. Now I will reach for the atlas. The atlas is far more inclusive than the term<i>hematology</i>would suggest. There are sections on solid tumors as found in the bone marrow and biopsy specimen and touch preparations. The atlas covers the gamut of RBCs, WBCs, and storage diseases. The inclusion of sections dealing with artifacts and parasitic infections further enhances the book's usefulness. The plates accurately depict what comes through the hematology laboratory. Not all are in the same
Transgenic rearranged T cell receptor gene inhibits lymphadenopathy and accumulation of CD4-CD8-B220+ T cells in lpr/lpr mice.
Authors: J D Mountz, T Zhou, J Eldridge, K Berry, H Blüthmann
Journal: The Journal of Experimental Medicine (1990)

The lpr gene in homozygous form induces development of CD4-CD8-B220+ T cells and lymphadenopathy in MRL and C57BL/6 mice. Although the propensity for excessive production of T cells is related to an intrinsic T cell defect, a thymus is also required because neonatal thymectomy eliminates lymphadenopathy. Recent evidence suggests that excessive production and release of autoreactive T cells from the thymus of lpr/lpr mice might lead to downregulation of CD4 and CD8 as a "fail safe" tolerance mechanism that occurs during late thymic or post-thymic development. To test this hypothesis, T cell receptor (TCR) transgenic mice that produce large numbers of immature thymocytes recognizing the H-2Db and male H-Y antigens were backcrossed with C57BL/6-lpr/lpr mice and MRL-lpr/lpr mice. It was predicted that Db male lpr/lpr mice would produce large numbers of autoreactive T cells during early thymic development that would lead to an accelerated lymphoproliferative disease. In contrast, Db female lpr/lpr mice would produce large numbers of Db H-Y-reactive T cells, but might not develop lymphadenopathy because the male H-Y antigen would not be present. Unexpectedly, there was complete elimination of lymphadenopathy in both male and female TCR transgenic lpr/lpr mice. The elimination of lymphadenopathy was not due to a failure of thymic maturation since the thymus of H-2Db female lpr/lpr mice contained nearly normal numbers of mature thymocytes. Elimination of lymphadenopathy was also not due to a lack of autoreactive T cells in the peripheral lymph nodes (LN) since there was an increased syngeneic mixed lymphocyte proliferative response of LNT cells from transgenic lpr/lpr compared with +/+ mice in vitro. Hypergammaglobulinemia and autoantibody production in the transgenic lpr/lpr was present at levels comparable with or higher than control nontransgenic lpr/lpr mice, suggesting a dissociation of autoantibody production from the lymphoproliferative disease in the TCR transgenic mice. Conversely, the development of lymphadenopathy and production of CD4-CD8-B220+ T cells appear to be intimately linked, as both were completely eliminated in T cells expressing the transgenic TCR. We propose that lymphoproliferation and production of CD4-CD8-6B2+ T cells in lpr/lpr mice is related to decreased expression of the TCR, and providing the T cells with a rearranged TCR transgene overcomes this defect.
Abstract A7: TARP-TCR-engineered T cells specifically kill HLA-A2 positive prostate and breast cancer cells.
Authors: Victoria Hillerdal, Berith Nilsson, Bjorn Carlsson, Fredrik Eriksson, Magnus Essand
Journal: Cancer Research (2013)

Abstract In order to produce genetically engineered T cells directed against prostate and breast cancer cells we have cloned the T cell receptor recognizing the human leukocyte antigen (HLA)-A2-restricted TARP4-13 epitope. TARP is a protein exclusively expressed in normal prostate epithelium and in adenocarcinomas of the prostate and breast. Peripheral blood T cells transduced with a lentiviral vector encoding the TARP-TCR proliferated well when exposed to peptide-specific stimuli. They exerted peptide-specific interferon-γ production and cytotoxic activity. Importantly, HLA-A2+ prostate and breast cancer cells expressing TARP were also killed, demonstrating that the TARP4-13 epitope is a physiologically relevant target for T cell therapy of prostate and breast cancer. In conclusion, we present the cloning of a TCR directed against a physiologically relevant HLA-A2 epitope of TARP. To our knowledge this is the first report on engineering of T cells with a TCR directed against an antigen specifically expressed by prostate cells. Citation Format: Victoria Hillerdal, Berith Nilsson, Bjorn Carlsson, Fredrik Eriksson, Magnus Essand.TARP-TCR-engineered T cells specifically kill HLA-A2 positive prostate and breast cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A7.
Note on the Treatment of Enlarged Cervical Glands
Authors: F. Jordan
Journal: BMJ (1872)

The various influences spoken of, acting through the different parts of the nervous system, impress immediately the sympathetic, and so alter the current of blood through the head: thus, while the face is pale, the larger vessels are throbbing, the head is hot, and the remedies which instinct suggests are cold and pressure to the part.In fact, of all the means which have been used to cure this trouble, the only one on which we can rely to procure relief is the wet bandage tied tightly round the head.The method must be instinctive, for it is universal, and has been used from all time.As our Shakespeare is often quoted to illustrate the morbid states of the body as well as the passions of the mind, he may be again conjured up to testify to the ancient practice of which I have been speaking.For example, in the scene between Hubert and Arthur in Aing y7ohz, the latter, when petitioning for the preservation of his eyes, says-" When your head did btut ache I kniit my handkerchief about your brows."And in OAch/to we have not only the remedy for headache given, but the cause.The former was the handkerchief about which the chief interest of the play centred."De'sdeioner.Why do vou speak so faintly ?Are you not well ?Otkello ....I have a pain upon my forehead here.
Aggravation of viral hepatitis by platelet-derived serotonin
Authors: Philipp A Lang, Claudio Contaldo, Panco Georgiev, Ashraf Mohammad El-Badry, Mike Recher, Michael Kurrer, Luisa Cervantes-Barragan, Burkhard Ludewig, Thomas Calzascia, Beatrice Bolinger, Doron Merkler, Bernhard Odermatt, Michael Bader, Rolf Graf, Pierre-Alain Clavien, Ahmed N Hegazy, Max Löhning, Nicola L Harris, Pamela S Ohashi, Hans Hengartner, Rolf M Zinkernagel, Karl S Lang
Journal: Nature Medicine (2008)
Effect of deoxycholic acid and ursodeoxycholic acid on lipid peroxidation in cultured macrophages.
Authors: P Ljubuncic, B Fuhrman, J Oiknine, M Aviram, A Bomzon
Journal: Gut (1996)

BACKGROUND: Kupffer cells are essential for normal hepatic homeostasis and when stimulated, they secrete reactive oxygen species, nitric oxide, eicosanoids, and cytokines. Some of these products are cytotoxic and attack nucleic acids, thiol proteins, or membrane lipids causing lipid peroxidation. Hydrophobic bile acids, such as deoxycholic acid (DCA), can damage hepatocytes by solubilising membranes and impairing mitochondrial function, as well as increasing the generation of reactive oxygen species. OBJECTIVES: The hypothesis that hydrophobic bile acids could stimulate Kupffer cells to increase their capacity to generate reactive oxygen species by measuring cellular lipid peroxidation was tested. Because the hydrophilic bile acid, ursodeoxycholic acid (UDCA) can block hydrophobic bile acid induced cellular phenomena, it was also hypothesised that UDCA could antagonise macrophage activation by hydrophobic bile acids to blunt their capacity to generate reactive oxygen species. METHODS: J-774A.1 murine macrophages were incubated for 24 hours with either 10(-5) M and 10(-4) M (final concentration) DCA alone, or 10(-4) M UDCA alone, or a mixture of 10(-4) M 1:1 molar ratio of DCA and UDCA. At the end of the incubation period, the culture medium was collected for determination of cellular lipid peroxidation by measuring the malondialdehyde (MDA) content in the medium with the thiobarbituric acid reactive substances assay. RESULTS: 10(-5) M and 10(-4) M DCA increased MDA generation by cultured macrophages. 10(-4) M UDCA alone did not increase MDA generation but blocked the peroxidative actions of DCA. CONCLUSIONS: Hydrophobic bile acids, after their hepatic retention, can oxidatively activate Kupffer cells to generate reactive oxygen species. Because UDCA can block this action, the beneficial effect of UDCA is, in part, related to its ability to act as an antioxidant.
Hepatitis C and human immunodeficiency virus infection
Authors: David L. Thomas
Journal: Hepatology (2002)

In the United States, an estimated 200,000 persons are infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). As the lives of HIV-infected persons have been prolonged by use of highly active antiretroviral therapy, liver disease has emerged as an important, and in some settings, the leading cause of morbidity and mortality. Human immunodeficiency virus infection appears to adversely affect all stages of hepatitis C infection, leading to increased viral persistence and accelerated progression of HCV-related liver disease. In turn, hepatitis C may affect the management of HIV infection, increasing the incidence of liver toxicity caused by antiretroviral medications. The medical management of hepatitis C in HIV-infected persons remains controversial, in part because of the complexity of both infections and potential drug interactions, but chiefly because there is so little published information. Nonetheless, the burden of liver disease is too high to delay management of HIV/HCV-coinfected persons while awaiting better data. Instead, the management of hepatitis C today must be based on data generated on persons without HIV and an understanding of both infections. Properly designed studies of therapy in HIV/HCV-coinfected persons are needed to help guide management of these patients in the future.
New QOF glycaemia targets are achievable and evidence based
Authors: S. Griffin, J. Graffy
Journal: BMJ (2009)

Lehman and Krumholz suggest that the revised targets for glycated haemoglobin in the quality and outcomes framework (QOF) pose a risk to people with diabetes, many of whom will need insulin if 50% are to achieve values of 7.0% or less.1 Fortunately, glycaemic control is rather better than they realise: in …
Serotonergic Modulation of Ventilation and Upper Airway Stability in Obese Zucker Rats
Authors: HITOSHI NAKANO, ULYSSES J. MAGALANG, SHIN-DA LEE, JOHN A. KRASNEY, GASPAR A. FARKAS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

To elucidate the role of serotonin in the maintenance of normal breathing and upper airway (UA) patency in obesity, we studied the effects of systemic administration of ritanserin, a serotonin (5-HT) 2A and 2C receptor antagonist, on ventilation (V˙ e) during room air breathing and during hypoxic (10% O2) and hypercapnic (4% CO2) ventilatory challenges in awake young (6–8 wk) and older (7–8 mo) obese and lean Zucker (Z) rats. Older obese Z rats adopted a more rapid shallow breathing pattern compared with older lean rats. The administration of ritanserin (1 mg/kg intraperitoneally) to older obese rats resulted in a reduction in V˙ e (439 ± 35 [SD] to 386 ± 41 ml/kg/min, p < 0.01), a decrease in respiratory rate, a prolongation of inspiratory time, and an increase in V˙ o 2 (16.4 ± 1.7 to 18.2 ± 1.9 ml/kg0.75/min, p < 0.05) during room air breathing. By comparison, it had little effect on ventilation in young lean and obese Z or older lean Z rats. Ritanserin also had no effect on ventilatory responses to either hypoxia or hypercapnia in young or older lean and obese Z rats. The collapsibility of the isolated UA was examined in older Z rats. The pharyngeal critical pressure (Pcrit) of older obese rats was significantly greater than that of lean rats (p < 0.05), indicating that obese rats have more collapsible UA than lean rats. The administration of ritanserin significantly increased Pcrit in older obese rats ( − 1.6 ± 0.3 to − 0.8 ± 0.2 cm H2O, p < 0.01) and in lean rats ( − 3.1 ± 1.0 to − 2.4 ± 0.6 cm H2O, p < 0.05). We suggest that the 5-HT2A/2C receptor subtype plays an important role in the maintenance of UA stability and normal breathing in obesity, and we speculate that older obese Z rats may have augmented serotonergic control of UA dilator muscles as a mechanism to prevent pharyngeal collapse.
Book Review The Measure of America: American Human Development Report, 2008–2009 Edited by Sarah Burd-Sharps, Kristen Lewis, and Eduardo Borges Martins. 246 pp., illustrated. New York, Social Science Research Council/Columbia University Press, 2008. $75 (cloth); $24.95 (paper). 978-0-231-15494-9 (cloth); 978-0-231-15495-6 (paper).
Authors: Christopher Simms
Journal: New England Journal of Medicine (2009)
Diagnostic Significance of Endoscopic Biopsy in Crohn's Disease
Authors: R. Pötzi, M. Walgram, H. Lochs, H. Holzner, A. Gangl
Journal: Endoscopy (1989)

We investigated the diagnostic value of biopsies taken from Crohn's lesions such as ulcers, aphthoid lesions, cobble-stone epithelium and "pseudopolyps". One hundred and forty-six colonoscopies performed in 141 patients with Crohn's disease (CD) were analyzed. Biopsies were taken during colonoscopy from different gross lesions. Histologic confirmation of CD by granulomas and microgranulomas was obtained in 36 cases from 146 colonoscopies (24.7%). In 80 investigations (54.8%) the histologic findings were consistent with, but not diagnostic of, CD, in 30 cases (20.5%) histology was non-diagnostic. The lesions most likely to contain granulomas were ulcers and we therefore conclude that biopsies taken from ulcer are diagnostically superior to those taken from other lesions seen in CD.
RASA1 maintains the lymphatic vasculature in a quiescent functional state in mice
Authors: Philip E. Lapinski, Sunkuk Kwon, Beth A. Lubeck, John E. Wilkinson, R. Sathish Srinivasan, Eva Sevick-Muraca, Philip D. King
Journal: Journal of Clinical Investigation (2012)

RASA1 (also known as p120 RasGAP) is a Ras GTPase-activating protein that functions as a regulator of blood vessel growth in adult mice and humans. In humans, RASA1 mutations cause capillary malformation-arteriovenous malformation (CM-AVM); whether it also functions as a regulator of the lymphatic vasculature is unknown. We investigated this issue using mice in which Rasa1 could be inducibly deleted by administration of tamoxifen. Systemic loss of RASA1 resulted in a lymphatic vessel disorder characterized by extensive lymphatic vessel hyperplasia and leakage and early lethality caused by chylothorax (lymphatic fluid accumulation in the pleural cavity). Lymphatic vessel hyperplasia was a consequence of increased proliferation of lymphatic endothelial cells (LECs) and was also observed in mice in which induced deletion of Rasa1 was restricted to LECs. RASA1-deficient LECs showed evidence of constitutive activation of Ras in situ. Furthermore, in isolated RASA1-deficient LECs, activation of the Ras signaling pathway was prolonged and cellular proliferation was enhanced after ligand binding to different growth factor receptors, including VEGFR-3. Blockade of VEGFR-3 was sufficient to inhibit the development of lymphatic vessel hyperplasia after loss of RASA1 in vivo. These findings reveal a role for RASA1 as a physiological negative regulator of LEC growth that maintains the lymphatic vasculature in a quiescent functional state through its ability to inhibit Ras signal transduction initiated through LEC-expressed growth factor receptors such as VEGFR-3.
Expanded G4C2 repeats linked to C9ORF72ALS and FTD form length-dependent RNA foci, sequester RNA binding proteins and are neurotoxic
Authors: Youn-Bok Lee, Han-Jou Chen, João N Peres, Jorge Gomez, Valentina Sardone, Agnes L Nishimura, Emma Scotter, Caroline Vance, Maja Štalekar, Yoshitsugu Adachi, Claire Troakes, Jack Miller, Bradley Smith, Frank Hirth, Boris Rogelj, Corinne Houart, Christopher E Shaw
Journal: Molecular Neurodegeneration (2013)

Background The GGGGCC (G4C2) intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) [1,2]. The mechanism by which the G4C2 intronic repeats cause neurodegeneration is unknown. Decreased tissue levels of the C9ORF72 transcript implicate a loss of protein function due to haploinsufficiency, intranuclear neuronal RNA foci have been observed in ALS and FTD tissues, suggesting that G4C2 RNA may be toxic [1].
Electron microscopy in the cytological examination of metastatic pleural effusions.
Authors: M Legrand, R Pariente
Journal: Thorax (1976)

In a previous publication the ultrastructure of pleural effusions in cases of pleural mesothelioma was reported. The same method has now been applied to a study of effusions produced by pleural metastases. The findings are considered sufficiently conclusive to justify the use of electron microscopic cytology in determining the nature and sometimes the origin of such effusions.
Non‐Hodgkin's lymphoma presenting as an endobronchial tumor: Report of eight cases and literature review
Authors: Anna Solomonov, Tsila Zuckerman, Ludmila Goralnik, Yehudit Ben‐Arieh, Jacob M. Rowe, Mordechai Yigla
Journal: American Journal of Hematology (2008)

Abstract Non‐Hodgkin's lymphoma (NHL) involving the endobronchial tree is uncommon, and the initial presentation of NHL as an endobronchial tumor is extremely rare. In a series of 441 patients with newly diagnosed non‐Hodgkin's lymphoma over a 7‐year period, we reviewed the clinical features of eight patients who presented with an endobronchial tumor. All patients had local pulmonary disease without extrathoracic involvement. The major presenting symptoms were dyspnea, chest pain, cough, and hoarseness. None of the patients had systemic symptoms. Radiographs revealed lobar collapse in all cases. Five patients had mediastinal masses and three had isolated endobronchial lesions. Although MALT lymphoma is the most common primary pulmonary lymphoma, it was present in only one of our patients, while seven patients had aggressive lymphoma. All patients received chemotherapy. Six of the eight patients responded favorably to treatment with complete remission. The prognosis of patients with isolated endobronchial lymphoma is not worse than other local presentations of lymphoma. Bronchoscopic examination with biopsy is essential to differentiate these lesions from primary bronchongenic carcinoma. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Modulation of atherosclerosis in mice by Toll-like receptor 2
Authors: A. E. Mullick
Journal: Journal of Clinical Investigation (2005)

Epidemiologic evidence has established a relationship between microbial infection and atherosclerosis. Mammalian TLRs provide clues on the mechanism of this inflammatory cascade. TLR2 has a large ligand repertoire that includes bacterial-derived exogenous and possibly host-derived endogenous ligands. In atherosclerosis-susceptible low-density lipoprotein receptor-deficient (Ldlr-/-) mice, complete deficiency of TLR2 led to a reduction in atherosclerosis. However, with BM transplantation, loss of TLR2 expression from BM-derived cells had no effect on disease progression. This suggested that an unknown endogenous TLR2 agonist influenced lesion progression by activating TLR2 in cells that were not of BM cell origin. Moreover, with intraperitoneal administration of a synthetic TLR2/TLR1 agonist, Pam3CSK4, disease burden was dramatically increased in Ldlr-/- mice. A complete deficiency of TLR2 in Ldlr-/- mice, as well as a deficiency of TLR2 only in BM-derived cells in Ldlr-/- mice, led to striking protection against Pam3CSK4-mediated atherosclerosis, suggesting a role for BM-derived cell expression of TLR2 in transducing the effects of an exogenous TLR2 agonist. These studies support the concept that chronic or recurrent microbial infections may contribute to atherosclerotic disease. Additionally, these data suggest the presence of host-derived endogenous TLR2 agonists.
Detection of Hepatocellular Carcinoma Using Glycomic Analysis
Authors: Radoslav Goldman, Habtom W. Ressom, Rency S. Varghese, Lenka Goldman, Gregory Bascug, Christopher A. Loffredo, Mohamed Abdel-Hamid, Iman Gouda, Sameera Ezzat, Zuzana Kyselova, Yehia Mechref, Milos V. Novotny
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Hepatocellular carcinoma (HCC) represents an increasing health problem in the United States. Serum α-fetoprotein, the currently used clinical marker, is elevated in only ∼60% of HCC patients; therefore, the identification of additional markers is expected to have significant public health impact. The objective of our study was to quantitatively assess N-glycans originating from serum glycoproteins as alternative markers for the detection of HCC. Experimental Design: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for quantitative comparison of 83 N-glycans in serum samples of 202 participants (73 HCC cases, 77 age- and gender-matched cancer-free controls, and 52 patients with chronic liver disease). N-glycans were enzymatically released from serum glycoproteins and permethylated before mass spectrometric quantification. Results: The abundance of 57 N-glycans was significantly altered in HCC patients compared with controls. The sensitivity of six individual glycans evaluated for separation of HCC cases from population controls ranged from 73% to 90%, and the specificity ranged from 36% to 91%. A combination of three selected N-glycans was sufficient to classify HCC with 90% sensitivity and 89% specificity in an independent validation set of patients with chronic liver disease. The three N-glycans remained associated with HCC after adjustment for chronic viral infection and other known covariates, whereas the other glycans increased significantly at earlier stages of the progression of chronic viral infection to HCC. Conclusion: A set of three identified N-glycans is sufficient for the detection of HCC with 90% prediction accuracy in a population with high rates of hepatitis C viral infection. Further evaluation of a wider clinical utility of these candidate markers is warranted.