tbuckley/cabot-search huggingface dataset:
The export of immunoglobulin D by human neoplastic B lymphocytes.
Authors: F K Stevenson, G T Stevenson, A L Tutt
Journal: The Journal of Experimental Medicine (1983)

An investigation has been made into the ability of human neoplastic B lymphocytes expressing surface IgM and IgD to export IgD in culture. Cells that expressed surface Ig of the lambda light chain type frequently exported IgD (10/12 patients), whereas cells expressing surface Ig of the kappa light chain type exported no IgD, although most (8/11 patients) were able to export IgM. It appears, therefore, that in most of the 23 cases studied, cells synthesizing IgD with lambda light chains can both express and export IgD, whereas those synthesizing IgD kappa can only insert it into the surface membrane. This finding and the known preponderance of lambda in plasma IgD imply that the possession of a lambda chain facilitates the IgD secretory pathway, a conclusion that implicates a control mechanism subsequent to the surface/secretory dichotomy arising from different splicings of heavy chain messenger RNA.
Death and Deliverance: 'Euthanasia' in Germany, c. 1900-1945
Authors: Henry Friedlander
Journal: JAMA (1995)

Convention has defined the Holocaust as the mass murder of the European Jews, who were killed simply because they were Jews. This definition is accurate in that it draws a distinction between Jews whose murder as a group was based on their heredity and Jews who were persecuted and killed as individuals for their political affiliation, religious beliefs, personal lifestyles, or resistance activities. But this definition is misleading if it excludes others also murdered on the basis of heredity, as, for example, the European Gypsies. Furthermore, the Nazi regime also excluded, persecuted, and murdered institutionalized patients suffering from mental and physical disabilities, who were consigned to extermination as a biological group; heredity determined their fate as much as it did that of Jews and Gypsies. In fact, the handicapped were the first victims killed on the assembly line in Nazi Germany. The technique of mass murder using gas chambers and
Abstract 3844: Targeting macrophages as a novel therapeutic approach for malignant pleural mesothelioma
Authors: Nikita S. Kolhatkar, Magnus Johansson, Dario Barbone, Adam Yagui-Beltran, Raphael Bueno, David J. Sugarbaker, David M. Jablons, V. Courtney Broaddus, Lisa M. Coussens
Journal: Cancer Research (2010)

Abstract Mesothelioma is a life-threatening tumor, induced by inhalation of asbestos fibers that is largely resistant to most chemotherapeutic drugs. Using a combination of immunohistochemistry and flow cytometry, we have evaluated both the presence and composition of leukocytes residing in human mesotheliomas, and have found that 1) epithelioid and mixed mesothelioma tumor subtypes contain higher percentages of CD45+ leukocytes than sarcomatous tumors, and 2) macrophages represent the most abundant immune cell subtype in mesothelioms, regardless of type (31 ± 4.6% of total CD45+). Indeed, the percentage of macrophages in mesotheliomas exceeded that found in other thoracic malignancies thus far evaluated (NSCLC cancer, 9%; esophageal, 4%). In view of recent data indicating that macrophages potentiate cancer development in some settings, and that macrophages can be targeted therapeutically to minimize some aspects of tumor progression, we investigated whether macrophages could be targeted to alter the chemosensitivity of human mesotheliomas. To address this question, we adapted a 3-dimensional (3D) spheroid growth model, enabling heterotypic culture of mesotheliomal cells and macrophages. Our data indicate that mesothelioma chemoresistance can be lowered by co-incubation with macrophages. However, the magnitude of the altered response is dependent upon macrophage phenotype. Macrophage phenotype and bioactivity is modulated by TH1 and TH2 cytokine exposure that in turn regulate either an M1 (IFN-γ &amp; LPS) or M2 (IL-4) phenotype. M1-polarized macrophages increased the response of malignant mesothelioma spheroids to pro-apoptotic chemotherapeutic agents, including gemcitabine. Furthermore, our preliminary data indicate that primary human tumor-associated macrophages, isolated from untreated malignant mesotheliomas, exhibit similar pro-apoptotic effects when polarized with M1 cytokines, indicating that cytokine re-polarization of macrophages in mesotheliomas to an M1 phenotype could enhance efficacy of cytotoxic therapy. This work was supported by grants from the NCI and a DoD Mesothelioma Program grant PR080717 to Broaddus and Coussens Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3844.
Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells
Authors: Satoshi Uematsu, Myoung Ho Jang, Nicolas Chevrier, Zijin Guo, Yutaro Kumagai, Masahiro Yamamoto, Hiroki Kato, Nagako Sougawa, Hidenori Matsui, Hirotaka Kuwata, Hiroaki Hemmi, Cevayir Coban, Taro Kawai, Ken J Ishii, Osamu Takeuchi, Masayuki Miyasaka, Kiyoshi Takeda, Shizuo Akira
Journal: Nature Immunology (2006)
3,3′-Diindolylmethane Enhances Chemosensitivity of Multiple Chemotherapeutic Agents in Pancreatic Cancer
Authors: Sanjeev Banerjee, Zhiwei Wang, Dejuan Kong, Fazlul H. Sarkar
Journal: Cancer Research (2009)

Clinical management of pancreatic cancer is a major problem, which is in part due to both de novo and acquired resistance to conventional therapeutics. Here, we present in vitro and in vivo preclinical evidence in support of chemosensitization of pancreatic cancer cells by 3,3-diindolylmethane (DIM), a natural compound that can be easily obtained by consuming cruciferous vegetables. DIM pretreatment of pancreatic cancer cells led to a significantly increased apoptosis (P < 0.01) with suboptimal concentrations of chemotherapeutic agents (cisplatin, gemcitabine, and oxaliplatin) compared with monotherapy. It is known that resistance to chemotherapy in pancreatic cancer is associated with constitutively activated nuclear factor-kappaB (NF-kappaB), which becomes further activated by chemotherapeutic drugs. Our data provide mechanistic evidence for the first time showing that DIM potentiates the killing of pancreatic cancer cells by down-regulation of constitutive as well as drug-induced activation of NF-kappaB and its downstream genes (Bcl-xL, XIAP, cIAP, and survivin). Most importantly, using an orthotopic animal model, we found reduction in tumor size (P < 0.001) when DIM was given in combination with oxaliplatin compared with monotherapy. This was accompanied by loss of phospho-p65 and down-regulation of NF-kappaB activity and its downstream genes (Bcl-xL, survivin, and XIAP), which correlated with reduced cell proliferation (as assessed by Ki-67 immunostaining of tumor specimens) and evidence of apoptosis [as assessed by poly(ADP-ribose) polymerase cleavage and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining]. These results provide strong in vivo evidence in support of our hypothesis that DIM could abrogate chemotherapeutic drug (cisplatin, gemcitabine, and/or oxaliplatin)-induced activation of NF-kappaB, resulting in the chemosensitization of pancreatic tumors to conventional therapeutics.
Trophic influence of the sympathetic nervous system on the rat portal vein.
Authors: O Aprigliano, K Hermsmeyer
Journal: Circulation Research (1977)

Adrenergic denervation of the rat portal vein was produced in vivo by the sympatholytic agent 6-hydroxydopamine (6-OHDA). Treatment of rats with 6-OHDA decreased the responses of the portal veins to nerve stimulation, reduced 3H-norepinephrine (NE) uptake, and decreased catecholamine fluorescence, indicating that partial adrenergic denervation was achieved. The main findings of this study indicate that the in vivo denervation produced: (1) a (time-dependent) increase in sensitivity of the veins to NE, which was not of prejunctional origin, (2) an increase in sensitivity to BaC12, and (3) a partial depolarization of the myovascular cells. The results suggest that the in vivo denervation of the portal veins by 6-OHDA produces a postjunctional alteration, which may be due to the removal of a trophic influence of the sympathetic nervous system. It is proposed that the partial depolarization and associated ionic changes may be components of the mechanism. These results provide the first direct evidence that membrane excitability changes are involved in trophic nerve-muscle interactions in blood vessels.
Generation of Dual Resistance to 4-Hydroperoxycyclophosphamide and Methotrexate by Retroviral Transfer of the Human Aldehyde Dehydrogenase Class 1 Gene and a Mutated Dihydrofolate Reductase Gene
Authors: Naoko Takebe, Shi-Cheng Zhao, Debasis Adhikari, Shin Mineishi, Michel Sadelain, John Hilton, Michael Colvin, Debabrata Banerjee, Joseph R. Bertino
Journal: Molecular Therapy (2001)

The genetic transfer of drug resistance to hematopoietic cells is an attractive approach to overcoming myelosuppression caused by high-dose chemotherapy. Because cyclophosphamide (CTX) and methotrexate (MTX) are commonly used non-cross-resistant drugs, generation of dual drug resistance in hematopoietic cells that allows dose intensification may increase anti-tumor effects and circumvent the emergence of drug-resistant tumors. We constructed a retroviral vector containing both a human cytosolic ALDH-1 cDNA and a human doubly mutated DHFR cDNA (Phe22/Ser31; termed F/S in the description of constructs) to generate increased resistance to both CTX and MTX. Infection of NIH3T3 cells resulted in increased resistance to both 4-hydroperoxycyclophosphamide (4HC) (1.9 +/- 0.1-fold) and MTX (73 +/- 2.8-fold). Transduced human CD34(+) enriched hematopoietic progenitor cells were also resistant to both 4HC and MTX by CFU-GM readout. Lethally irradiated mice transplanted with SFG-ALDH-IRES-F/S or mock-transduced bone marrow cells were treated with high-dose pulse CTX or high-dose CTX/MTX. Animals receiving marrow not transduced with ALDH-1 or mutated DHFR cDNA died from CTX or CTX/MTX toxicity, whereas mice transduced with ALDH-1 and mutated DHFR cDNA-containing marrow were able to tolerate the same doses of CTX or CTX/MTX treatment posttransplant. These data taken together indicate that ALDH-1 overexpression and mutant DHFR increased both 4HC and MTX resistance in vitro and in the in vivo mouse model. This construct may be useful for protecting patients from high-dose CTX- and MTX-induced myelosuppression.
Coronary risk factors in people from the Indian subcontinent living in West London and their siblings in India
Authors: D.J. Patel, M. Winterbotham, R.P. Britt, G.C. Sutton, D. Bhatnagar, M.I. Mackness, F. Creed, B. Tomenson, P.N. Durrington, I.S. Anand, G.S. Wander, Y. Chandrashekhar, J.E. Keil
Journal: The Lancet (1995)
Surface expression of a heterologous phosphatase complements CD45 deficiency in a T cell clone.
Authors: D G Motto, M A Musci, G A Koretzky
Journal: The Journal of Experimental Medicine (1994)

Expression of CD45, the major transmembrane protein tyrosine phosphatase expressed on lymphoid cells, is required for optimal T cell receptor (TCR) signal transduction. We and others recently have demonstrated that surface expression of the cytoplasmic domain of CD45 in the absence of its extracellular and transmembrane domains is sufficient to restore TCR-mediated signaling events in CD45-deficient cell lines. Here we demonstrate that a single domain nonreceptor tyrosine phosphatase from yeast expressed as a chimeric protein with the extracellular and transmembrane domains of a major histocompatibility complex class I molecule also is able to restore proximal and distal TCR-mediated signal transduction events in the CD45-deficient T cell line J45.01. Ligation of the TCR on the cell line expressing the yeast phosphatase chimera results in the induction of protein tyrosine kinase activity, soluble inositol phosphate generation, and expression of the CD69 activation antigen. Furthermore, a phosphatase-inactive version of this molecule is unable to restore signal transduction, providing the first formal evidence that plasma membrane associated tyrosine phosphatase activity is required for TCR-mediated signaling.
Busulphan and bone marrow depression.
Authors: D. J. Weatherall, D. A. Galton, H. E. Kay
Journal: BMJ (1969)

lion Act.She said that these fell into three categories: " To know and understand its provisions; to apply the knowledge objec- tively ; and to avoid using it if at all pos- sible."What an extraordinary statement !The Abortion Act is the law of the land and 'has already proved of immense benefit to many of my patients.It is there to be used and to be applied uniformly throughout the country.It is the antagonism to abortion reform of many doctorse particularly N.H.S. consultants in certain parts of the country, that creates long queues for abortion.It is only necessary for two doctors, a general practitioner and his colleague, to sign certi- ficate A-the patient is then ready for opera- tion.A great deal of valuable time is now being wasted in referring these unfortunate patients to psychiatrists, and the gynaeco- logist could perform three abortions in the time that he takes, unnecessarily, to investigate one case.Some psychiatrists will not approve termination under the Act but will admit the patient to a mental hospital for supportive therapy.What nonsense !If all doctors, general practitioners and consultants, put their patient's welfare before their own religious and biased cobwebbed ideas on abortion, then the new Act would present no problems at all.A patient for termination of pregnancy would appear in hospital as an acute appendix does today, and would be dealt with as quickly and without question.-Iam, etc.,
Doctor who carried out three abortions as favour to colleague is allowed to resume unrestricted practice
Authors: C. Dyer
Journal: BMJ (2014)

A consultant obstetrician and gynaecologist who three times evacuated the womb of a woman who may have been carrying a viable pregnancy as a “favour” to a colleague may resume unrestricted practice after spending 18 months working under imposed conditions, the Medical Practitioners Tribunal Service has decided.

Mohamed Al-Samarraie’s fitness to practise was judged to be impaired by a tribunal service panel in 2012, after he admitted providing inappropriate care to “patient A” in three different pregnancies over a 15 month period from 2005 to 2007.

On each occasion the woman, from Sudan, had been brought to Al-Samarraie by …
D - Penicillamine-induced pemphigus foliaceus with autoantibodies to desmoglein-1 in a patient with mixed connective tissue disease
Authors: Pablo F. Peñas, Guadalupe F. Buezo, Inmaculada Carvajal, Esteban Daudén, Argelia López, Luis A. Diaz
Journal: Journal of the American Academy of Dermatology (1997)
Spontaneous Renal Apoplexy with Resuscitation after Cardiac Arrest
Authors: S. L. Governale, A. G. Rink
Journal: BMJ (1944)

atmosphere; thus the airman lives in civilian hotels, and after the day's programme of rehabilitation he is free to go out, untrammelled by sentries, camp gates, and the like, the only restriction being the requirement to return to his billet by 10.30 p.m. Late passes and sleeping-out passes are, however, available in reasonable numbers.A valuable adjunct to the method of rehabilitation is pro- vided by the attitude of the physical training instructors, who, by their continued enthusiasm and high morale, form models of deportment and zest; and these qualities are reflected to
Chronic granulomatous disease due to a defect in the cytosolic factor required for nicotinamide adenine dinucleotide phosphate oxidase activation.
Authors: J T Curnutte, R L Berkow, R L Roberts, S B Shurin, P J Scott
Journal: Journal of Clinical Investigation (1988)

The superoxide-generating enzyme of human neutrophils, NADPH oxidase, is present in a dormant state in unstimulated neutrophils. It can be converted to an active form in a cell-free system if both the plasma membrane and cytosol fractions are incubated together in the presence of arachidonic acid. This system was used to determine the nature of the biochemical defect in seven patients with the autosomal recessive, cytochrome b-positive form of chronic granulomatous disease (CGD). A severe deficiency in the cytosol factor was identified in each patient. The defective activity was not caused by the presence of an inhibitor, nor could it be restored to normal by combining cytosol fractions from different patients. In contrast, the membrane fractions from all seven patients contained normal levels of NADPH oxidase when activated in the presence of control cytosol. Of family members tested (obligate heterozygotes for this disorder), seven of eight had intermediate levels of cytosol factor activity. The respiratory burst defect in this form of CGD is caused by an abnormality in the cytosolic factor required for NADPH oxidase activation.
Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia
Authors: Alireza Eghtedar, Srdan Verstovsek, Zeev Estrov, Jan Burger, Jorge Cortes, Carol Bivins, Stefan Faderl, Alessandra Ferrajoli, Gautam Borthakur, Solly George, Peggy A. Scherle, Robert C. Newton, Hagop M. Kantarjian, Farhad Ravandi
Journal: Blood (2012)
Seasonality trends of scabies in a young adult population: a 20-year follow-up
Authors: D. Mimouni, O.E. Ankol, N. Davidovitch, M. Gdalevich, E. Zangvil, I. Grotto
Journal: British Journal of Dermatology (2003)

Scabies is not a notifiable disease in most countries. Therefore, its seasonality trends are usually estimated and may be inaccurate.To determine the seasonality of scabies over the long term in a large military population, including all of the Israel Defence Forces personnel.For the last two decades, the Israel Defence Forces have mandated the routine reportage of every case of scabies infestation in soldiers to the Epidemiology Department of the Army Health Branch. This database was used in the present study to analyse the incidence of scabies by season. Scabies was defined according to the report by a military physician based on the typical clinical presentation, relevant epidemiological data and, in most cases, microscopic visualization of the mite.The person-time incidence of scabies was higher in winter than summer (P < 0.001). The overall risk ratio was 1.31 (95% confidence interval 1.28-1.33). Sensitivity analysis indicated that no single year was an important source of disease heterogeneity.Scabies in a young adult population is more frequent in the cooler months of the year.
Disturbances of pulmonary function after acute myocardial infarction.
Authors: M. C. Pain, M. Stannard, G. Sloman
Journal: BMJ (1967)

and observations of our own (Sloman et al., 1966) have shown a high incidence of arterial hypoxaemia in patients studied after myocardial infarction.McNicol et al. suggested that pulmonary congestion with venoarterial shunting was the basic cause of this hypoxaemia and that treatment with diuretics would improve blood oxygenation presumably by removing transudated fluid from the lungs.This paper reports studies carried out in an attempt to further elucidate the mechanisms responsible for disturbed pulmonary function after myocardial infarction.Measurements of arterial blood gases, uniformity of ventilation, ventilation-perfusion relations, and pulmonary haemodynamics were made shortly after the onset of myocardial infarction.
A5.14 The profile of axial spondyloarthritis patients according to fatigue level
Authors: J Zepa, I Bulina, V Lavrentjevs, J Arajs, E Sikora, L Nikitina-Zake, A Lejnieks, D Andersone
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> One of the most frequently reported symptoms by patients with axial spondyloarthritis (AxSpA) is disease-related fatigue. The role of fatigue and its degree during the course of AxSpA still remains a challenge. The objective of this study was to characterise the patients with AxSpA accordingly to the evaluation of disease-related fatigue. <h3>Materials and methods</h3> 120 patients were included in the cross-sectional study fulfilling the Assessment of Spondyloarthritis international Society (ASAS) classification criteria for AxSpA. Fatigue was evaluated using the first item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire. Patients were divided into two groups: with the evaluation of fatigue ≤5 and &gt;5. The following variables were chosen for characteristics of the groups: age, duration of the disease, the age of AxSpA onset, duration of morning stiffness, Ankylosing Spondylitis Disease Activity Score (ASDAS) (using c-reactive protein (CRP)), functional (BASFI) and metrological (BASMI) indices, the evaluation of enthesitis using the fourth item of the BASDAI questionnaire. <h3>Results</h3> The mean BASDAI fatigue score was 5.0 (SD 2.59). In our data, 44.2% of patients experienced severe fatigue (score &gt;5). The mean value of age, duration of morning stiffness, ASDAS, BASFI, BASMI and evaluation of enthesitis in the group with lower fatigue level was respectively 37.4 years (SD 9.63), 41 min (SD 37.97), 2.3 (SD 1.32), 2.2 (SD 2.09), 2.8 (SD 2.39) and 2.7 (SD 2.89). In the group with severe fatigue expression the mean age was 41.5 years (SD 10.09), duration of morning stiffness – 66.2 min (SD 43.06), ASDAS – 3.7 (SD 0.94), BASFI – 5.0 (SD 2.34), BASMI - 4.4 (SD 2.54), evaluation of enthesitis – 5.2 (SD 2.99). These variables were statistically different between groups. There was no difference between groups on duration of the disease and age of AxSpA onset. <h3>Conclusions</h3> Patients with severe fatigue had a higher level of the disease activity, functional disability and spinal mobility impairment. These results suggest that the level of fatigue can be used as one of the clinical signs which show the expression of systemic inflammation and induced impairment of mobility in the course of the disease independent of the disease duration.
Relationship of Smoking and Cardiovascular Risk Factors with Polypoidal Choroidal Vasculopathy and Age-related Macular Degeneration in Chinese Persons
Authors: Peter Cackett, Ian Yeo, Chui Ming Gemmy Cheung, Eranga N. Vithana, Doric Wong, Wan Ting Tay, E. Shyong Tai, Tin Aung, Tien Y. Wong
Journal: Ophthalmology (2010)