tbuckley/cabot-search huggingface dataset:
Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study
Authors: Marjolijn Duijvestein, Anne Christine W Vos, Helene Roelofs, Manon E Wildenberg, Barbara B Wendrich, Henricus W Verspaget, Engelina M C Kooy-Winkelaar, Frits Koning, Jaap Jan Zwaginga, Herma H Fidder, Auke P Verhaar, Willem E Fibbe, Gijs R van den Brink, Daniel W Hommes
Journal: Gut (2010)

<h3>Background and aim</h3> Mesenchymal stromal cells (MSCs) are pluripotent cells that have immunosuppressive effects both in vitro and in experimental colitis. Promising results of MSC therapy have been obtained in patients with severe graft versus host disease of the gut. Our objective was to determine the safety and feasibility of autologous bone marrow derived MSC therapy in patients with refractory Crohn9s disease. <h3>Patients and intervention</h3> 10 adult patients with refractory Crohn9s disease (eight females and two males) underwent bone marrow aspiration under local anaesthesia. Bone marrow MSCs were isolated and expanded ex vivo. MSCs were tested for phenotype and functionality in vitro. 9 patients received two doses of 1–2×10<sup>6</sup> cells/kg body weight, intravenously, 7 days apart. During follow-up, possible side effects and changes in patients9 Crohn9s disease activity index (CDAI) scores were monitored. Colonoscopies were performed at weeks 0 and 6, and mucosal inflammation was assessed by using the Crohn9s disease endoscopic index of severity. <h3>Results</h3> MSCs isolated from patients with Crohn9s disease showed similar morphology, phenotype and growth potential compared to MSCs from healthy donors. Importantly, immunomodulatory capacity was intact, as Crohn9s disease MSCs significantly reduced peripheral blood mononuclear cell proliferation in vitro. MSC infusion was without side effects, besides a mild allergic reaction probably due to the cryopreservant DMSO in one patient. Baseline median CDAI was 326 (224–378). Three patients showed clinical response (CDAI decrease ≥70 from baseline) 6 weeks post-treatment; conversely three patients required surgery due to disease worsening. <h3>Conclusions</h3> Administration of autologous bone marrow derived MSCs appears safe and feasible in the treatment of refractory Crohn9s disease. No serious adverse events were detected during bone marrow harvesting and administration.
Brain evolution by natural selection
Authors: Toru Shimizu
Journal: Behavioral and Brain Sciences (2006)

Principles of Brain Evolution (Striedter 2005) places little emphasis on natural selection. However, one cannot fully appreciate the diversity of brains across species, nor the evolutionary processes driving such diversity, without an understanding of the effects of natural selection. Had Striedter included more extensive discussions about natural selection, his text would have been more balanced and comprehensive.
Strong Association Between Time Watching Television and Blood Glucose Control in Children and Adolescents With Type 1 Diabetes
Authors: Alessandro Giannattasio, Francesca Lugani, Angela Pistorio, Nicola Minuto, Renata Lorini, Giuseppe d'Annunzio
Journal: Diabetes Care (2007)

We reply to Margeirsdottir et al. (1), reporting our experience in 237 type 1 diabetic Italian patients (139 male), aged (mean ± SD) 16.8 ± 7.1 years (range 1.8–36.3) with mean disease duration 9.0 ± 6.3 years (1.0–27.6), mean A1C 7.7 ± 1.1% (5.2–13.5), and mean insulin requirement 0.82 ± 0.24 units · kg−1 · day−1 (0.24–1.58).

Between January and March 2007, in all patients we evaluated by direct or telephone interviews the influence of leisure time in TV watching …
Alternating chemotherapy and radiotherapy for limited-stage intermediate and high-grade non-Hodgkin's lymphomas: Long-term results for 96 patients with tumors &gt; 5 cm
Authors: J.N. Munck, F. Dhermain, S. Koscielny, T. Girinsky, P. Carde, J. Bosq, D. Decaudin, M. Juliéron, J.M. Cosset, M. Hayat
Journal: Annals of Oncology (1996)
Enhanced expression of cyclo-oxygenase isoenzyme 2 (COX-2) in asthmatic airways and its cellular distribution in aspirin-sensitive asthma
Authors: A. Sousa, R. Pfister, P. E. Christie, S. J. Lane, S. M. Nasser, M. Schmitz-Schumann, T. H. Lee
Journal: Thorax (1997)

BACKGROUND: There are two isoforms of cyclo-oxygenase (COX), namely COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and in blood platelets. The metabolites derived from COX-1 are probably involved in cellular housekeeping functions. COX-2 is expressed only following cellular activation by inflammatory stimuli and is thought to be involved in inflammation. METHODS: The expression of COX-1 and COX-2 isoenzymes has been studied in the bronchial mucosa of 10 normal and 18 asthmatic subjects, 11 of whom had aspirin-sensitive asthma (ASA) and seven had non-aspirin-sensitive asthma (NASA) RESULTS: There was a significant fourfold and 14-fold increase, respectively, in the epithelial and submucosal cellular expression of COX-2, but not of COX-1, in asthmatic patients. There was no significant difference in the total number of cells staining for either COX-1 or COX-2 between subjects with ASA and NASA, but the number and percentage of mast cells that expressed COX-2 was significantly increased sixfold and twofold, respectively, in individuals with ASA. There was a mean fourfold increase in the percentage of COX-2 expressing cells that were mast cells in subjects with ASA and the number of eosinophils expressing COX-2 was increased 2.5-fold in these subjects. CONCLUSION: COX-2-derived metabolites may play an essential part in the inflammatory processes present in asthmatic airways and development of drugs targeted at this isoenzyme may have therapeutic potential in the treatment of asthma. Mast cells and eosinophils may also have a central role in the pathology of aspirin-sensitive asthma.
Disodium cromoglycate inhibits S mu--&amp;gt;S epsilon deletional switch recombination and IgE synthesis in human B cells.
Authors: R K Loh, H H Jabara, R S Geha
Journal: The Journal of Experimental Medicine (1994)

IgE synthesis requires interleukin 4 (IL-4) and a T-B cell interaction that involves the B cell antigen CD40 and its ligand expressed on activated T cells. IL-4 induces epsilon germline transcription whereas ligation of CD40 results in deletional S mu--&amp;gt;S epsilon switch recombination, expression of mature epsilon transcripts, and IgE synthesis and secretion. We demonstrate that disodium cromoglycate (DSCG), a drug commonly used for the prophylactic treatment of allergic disease, inhibits T cell-driven IgE synthesis by human B cells at concentrations readily achievable in the course of inhaled therapy for asthma. Inhibition of IgE synthesis by DSCG was not the result of drug toxicity because DSCG did not affect the viability of T and B cells or their proliferation to mitogens. DSCG did not interfere with CD40 ligand expression by T cells but clearly targeted the B cells because it inhibited IgE synthesis induced by anti-CD40 and IL-4 in populations of highly purified B cells. DSCG had no effect on the induction of epsilon germline transcripts by IL-4 but strongly inhibited CD40 mediated S mu--&amp;gt;S epsilon deletional switch recombination in IL-4-treated B cells as assayed by nested primer PCR. The effect of DSCG was not specific for CD40-mediated induction of IgE isotype switching because DSCG inhibited IgE synthesis as well as S mu--&amp;gt;S epsilon deletional switch recombination induced by hydrocortisone and IL-4 in B cells. Moreover, the effect of DSCG was not specific for IgE isotype switching because DSCG inhibited the synthesis of IgG4 by B cells sorted for lack of surface expression of IgG4 and stimulated with anti-CD40 and IL-4. DSCG caused only minimal inhibition (&amp;lt; 15%) of spontaneous IgE synthesis by lymphocytes from patients with the hyper-IgE syndrome and did not affect pokeweed mitogen-induced IgG and IgA synthesis by lymphocytes suggesting that it has little effect on B cells that have already undergone isotype switching. These results indicate that DSCG inhibits switching to IgE in B cells and suggest a novel potential mechanism for the prevention of allergic disease by DSCG.
Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1, and regulatory T-cell induction
Authors: Brian R. Rosborough, Dàlia Raïch-Regué, Benjamin M. Matta, Keunwook Lee, Boyi Gan, Ronald A. DePinho, Holger Hackstein, Mark Boothby, Hēth R. Turnquist, Angus W. Thomson
Journal: Blood (2013)
EXPERIMENTAL COMBINED VIRAL AND BACTERIAL INFECTION (INFLUENZA C AND HEMOPHILUS INFLUENZAE, TYPE B) IN EMBRYONATED EGGS
Authors: G. John Buddingh
Journal: The Journal of Experimental Medicine (1956)

Influenza C virus, J.J. strain, is readily propagated following intra-amniotic inoculation of embryonated eggs on the 14th day of incubation. The resulting infection is inapparent in that there is no obvious interference with normal embryonic development and no evidences of injury can be detected by the light microscope. Hemophilus influenzae, type b thrives luxuriantly in the amniotic fluid of embryonated eggs inoculated by the intra-amniotic route on the 15th day of incubation. The effects of the establishment of the bacterial infection in the embryo are noted by the occurrence of death, bacteriemia or characteristic inflammatory lesions in the form of purulent sinusitis, pharyngitis, tracheo-bronchitis and meningo-encephalitis. These lesions may occur singly or in various combinations. The incidence and severity of disease manifestations in infected embryos depends on the proportion of encapsulated and virulent bacilli in the inoculum, the number of infectious doses and the growth rate of the bacteria in the surrounding amniotic fluid. Combined viral and bacterial infection established by intra-amniotic inoculation with influenza C virus on the 14th followed by Hemophilus influenzae, type b on the 15th incubation day brings about a significant increase in the incidence and severity of disease manifestations in the embryos. Selective survival and marked acceleration of the growth rate of encapsulated and virulent elements of the bacterial population is promoted in the virus-infected embryos. The disease process appears to be entirely attributable to the bacterial component. There seems to be relatively little or no effect on influenza C virus by the accompanying proliferation of Hemophilus. The exact nature of the virus-induced influences which enhance the pathogenicity of the bacteria and favor the establishment of the infectious process under these circumstances remains to be determined.
Human erythrocyte hexokinase deficiency. Characterization of a mutant enzyme with abnormal regulatory properties.
Authors: G Rijksen, G E Staal
Journal: Journal of Clinical Investigation (1978)

In the erythrocytes of a patient with hereditary nonspherocytic hemolytic anemia, a homozygous expression of hexokinase deficiency was detected. The mutant enzyme was characterized by normal kinetic parameters with respect to its substrates, glucose and MgATP2-, normal pH optimum, normal heat stability at 40 degrees C, but abnormal behavior with respect to its regulation by glucose-1,6-diphosphate and inorganic phosphate, and an altered electrophoretic pattern. Interpretation of the results revealed the presence of two different hexokinases type I in normal human erythrocytes: one enzyme with a high affinity for glucose-1,6-diphosphate, the inhibition of which is regulated by inorganic phosphate; and another enzyme with a lower affinity for the inhibitor, not regulated by inorganic phosphate. The former enzyme was not detectable in the erythrocytes of the patient, whereas the presence of the latter enzyme could be demonstrated.
Flow cytometric analysis of cellular infiltrate from American tegumentary leishmaniasis lesions
Authors: A.M. Da-Cruz, A.L. Bertho, M.P. Oliveira-Neto, S.G. Coutinho
Journal: British Journal of Dermatology (2005)

Journal Article Flow cytometric analysis of cellular infiltrate from American tegumentary leishmaniasis lesions Get access A.M. Da‐Cruz, A.M. Da‐Cruz Laboratório de Imunopatologia, Departamento de Imunologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil *Instituto de Pesquisa Clínica Evandro Chagas (IPEC), FIOCRUZ, Rio de Janeiro, Brazil Alda Maria Da‐Cruz, Av. Brazil 4365, Pav. Leônidas Deane sala 408, Manguinhos, Rio de Janeiro‐RJ, Brazil, CEP 21040–900. E‐mail: alda@ioc.fiocruz.br Search for other works by this author on: Oxford Academic Google Scholar A.L. Bertho, A.L. Bertho Laboratório de Imunopatologia, Departamento de Imunologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil *Instituto de Pesquisa Clínica Evandro Chagas (IPEC), FIOCRUZ, Rio de Janeiro, Brazil Search for other works by this author on: Oxford Academic Google Scholar M.P. Oliveira‐Neto, M.P. Oliveira‐Neto Laboratório de Imunopatologia, Departamento de Imunologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil *Instituto de Pesquisa Clínica Evandro Chagas (IPEC), FIOCRUZ, Rio de Janeiro, Brazil Search for other works by this author on: Oxford Academic Google Scholar S.G. Coutinho S.G. Coutinho Laboratório de Imunopatologia, Departamento de Imunologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil *Instituto de Pesquisa Clínica Evandro Chagas (IPEC), FIOCRUZ, Rio de Janeiro, Brazil Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 3, 1 September 2005, Pages 537–543, https://doi.org/10.1111/j.1365-2133.2005.06647.x Published: 01 September 2005 Article history Accepted: 02 December 2004 Published: 01 September 2005
Orexin Regulates Bone Remodeling via a Dominant Positive Central Action and a Subordinate Negative Peripheral Action
Authors: Wei Wei, Toshiyuki Motoike, Jing Y. Krzeszinski, Zixue Jin, Xian-Jin Xie, Paul C. Dechow, Masashi Yanagisawa, Yihong Wan
Journal: Cell Metabolism (2014)
Epidemiological and Genetic Associations of Activated Factor XII Concentration With Factor VII Activity, Fibrinopeptide A Concentration, and Risk of Coronary Heart Disease in Men
Authors: Francesco Zito, Felicity Drummond, Sarah R. Bujac, M. Peter Esnouf, James H. Morrissey, Steve E. Humphries, George J. Miller
Journal: Circulation (2000)

Background —The relations of plasma activated factor XII (FXIIa) concentration and a common polymorphism (C46T) of the factor XII gene with hemostatic status and risk of coronary heart disease (CHD) were examined by prospective surveillance. Methods and Results —Genotyping for the C46T variant was performed in 2624 men 50 to 61 years of age who were free of CHD at baseline. The genotype distribution was as follows: CC, 56.7%; CT; 36.9%; and TT, 6.6%. Plasma FXIIa was measured by ELISA on 1745 samples collected 1 year after baseline; median levels were (ng/mL) CC, 2.0; CT, 1.4; and TT, 0.8 ( P &lt;0.0001). Respective values for plasma fibrinopeptide A (FPA, nmol/L) were 1.52, 1.35, and 1.15 ( P &lt;0.0001); for factor VII coagulant activity (FVIIc, % standard), 114.5, 116.2, and 109.3 ( P =0.02). Group differences in FVIIc were unchanged by adjustment for body mass index and serum triglycerides. Whereas CHD incidence did not differ significantly by genotype, rates (per 1000 person-years) by thirds of FXIIa distribution were for &lt;1.5 ng/mL, 7.2; for 1.5 to 2.0 ng/mL, 7.2; and for &gt;2.0 ng/mL, 13.6. Respective hazard ratios with the low third as reference group were 1.01 and 1.96 ( P =0.007), which were essentially unchanged after allowance for genotype, blood lipids, blood pressure, body mass index, FVIIc, and FPA. Conclusions —The C46T polymorphism is a determinant of FXIIa, FPA, and possibly FVIIc, suggesting that FXII influences the activity state of the coagulation pathway and FPA cleavage from fibrinogen in vivo. Plasma FXIIa is increased in middle-aged men at high risk of CHD.
Antiphospholipid syndrome associated with infections: clinical and microbiological characteristics of 100 patients
Authors: R Cervera
Journal: Annals of the Rheumatic Diseases (2004)

To describe and analyse the clinical characteristics of 100 patients with antiphospholipid syndrome (APS) associated with infections.Patients were identified by a computer assisted search (Medline) of published reports to locate all cases of APS published in English, Spanish, and French from 1983 to 2003. The bilateral Fisher exact test was used for statistics.59 female and 41 male patients were identified (mean (SD) age, 32 (18) years (range 1 to 78)): 68 had primary APS, 27 had systemic lupus erythematosus, two had "lupus-like" syndrome, two had inflammatory bowel disease, and one had rheumatoid arthritis. APS presented as a catastrophic syndrome in 40% of cases. The main clinical manifestations of APS included: pulmonary involvement (39%), skin involvement (36%), and renal involvement (35%; nine with renal thrombotic microangiopathy, RTMA). The main associated infections and agents included skin infection (18%), HIV (17%), pneumonia (14%), hepatitis C (13%), and urinary tract infection (10%). Anticoagulation was used in 74%, steroids in 53%, intravenous immunoglobulins in 20%, cyclophosphamide in 12%, plasma exchange in 12%, and dialysis in 9.6%. Twenty three patients died following infections and thrombotic episodes (16 with catastrophic APS). Patients given steroids had a better prognosis (p = 0.024). The presence of RTMA and requirement for dialysis carried a worse prognosis (p = 0.001 and p = 0.035, respectively).Various different infections can be associated with thrombotic events in patients with APS, including the potentially lethal subset termed catastrophic APS. Aggressive treatment with anticoagulation, steroids, and appropriate antibiotic cover is necessary to improve the prognosis.
Vaccination with a non-human random sequence amyloid oligomer mimic results in improved cognitive function and reduced plaque deposition and micro hemorrhage in Tg2576 mice
Authors: Suhail Rasool, Ricardo Albay, Hilda Martinez-Coria, Leonid Breydo, Jessica Wu, Saskia Milton, Sunit Misra, Andy Tran, Anna Pensalfini, Frank Laferla, Rakez Kayed, Charles G Glabe
Journal: Molecular Neurodegeneration (2012)

Abstract Background It is well established that vaccination of humans and transgenic animals against fibrillar Aβ prevents amyloid accumulation in plaques and preserves cognitive function in transgenic mouse models. However, autoimmune side effects have halted the development of vaccines based on full length human Aβ. Further development of an effective vaccine depends on overcoming these side effects while maintaining an effective immune response. Results We have previously reported that the immune response to amyloid oligomers is largely directed against generic epitopes that are common to amyloid oligomers of many different proteins and independent of a specific amino acid sequence. Here we have examined whether we can exploit this generic immune response to develop a vaccine that targets amyloid oligomers using a non-human random sequence amyloid oligomer. In order to study the effect of vaccination against generic oligomer epitopes, a random sequence oligomer (3A) was selected as it forms oligomers that react with the oligomer specific A11 antibody. Oligomer mimics from 3A peptide, Aβ, islet amyloid polypeptide (IAPP), and Aβ fibrils were used to vaccinate Tg2576 mice, which develop a progressive accumulation of plaques and cognitive impairment. Vaccination with the 3A random sequence antigen was just as effective as vaccination with the other antigens in improving cognitive function and reducing total plaque load (Aβ burden) in the Tg2576 mouse brains, but was associated with a much lower incidence of micro hemorrhage than Aβ antigens. Conclusion These results shows that the amyloid Aβ sequence is not necessary to produce a protective immune response that specifically targets generic amyloid oligomers. Using a non-human, random sequence antigen may facilitate the development of a vaccine that avoids autoimmune side effects.
Time from Prior Chemotherapy Enhances Prognostic Risk Grouping in the Second-line Setting of Advanced Urothelial Carcinoma: A Retrospective Analysis of Pooled, Prospective Phase 2 Trials
Authors: Guru Sonpavde, Gregory R. Pond, Ronan Fougeray, Toni K. Choueiri, Angela Q. Qu, David J. Vaughn, Guenter Niegisch, Peter Albers, Nicholas D. James, Yu-Ning Wong, Yoo-Joung Ko, Srikala S. Sridhar, Matthew D. Galsky, Daniel P. Petrylak, Ulka N. Vaishampayan, Awais Khan, Nicholas J. Vogelzang, Tomasz M. Beer, Walter M. Stadler, Peter H. O'Donnell, Cora N. Sternberg, Jonathan E. Rosenberg, Joaquim Bellmunt
Journal: European Urology (2012)
Occult Cardiac Contractile Dysfunction in Dystrophin-Deficient Children Revealed by Cardiac Magnetic Resonance Strain Imaging
Authors: M.W. Ashford, W. Liu, S.J. Lin, P. Abraszewski, S.D. Caruthers, A.M. Connolly, X. Yu, S.A. Wickline
Journal: Circulation (2005)

Background— Duchenne muscular dystrophy (DMD) is an inherited disease characterized by early onset of skeletal muscle degeneration and progressive weakness. Although dilated cardiomyopathy may occur during adolescence, it is often undetected early in its course because of physical inactivity and generalized debilitation. The purpose of this study was to apply the technique of cardiac magnetic resonance (CMR) tagging to detect occult cardiac dysfunction in young subjects with DMD by measuring myocardial strain and torsion. Methods and Results— Thirteen DMD pediatric subjects without clinically apparent heart disease and 9 age-matched healthy males were recruited. Each was scanned on a 1.5-T clinical scanner to acquire contiguous short-axis planes from the apex to the mitral valve plane and then 3 tagged images at base, midventricle, and apex. Global and segmental myocardial net twist and circumferential strain were computed with the use of 2D homogeneous strain analysis. Ventricular torsion was computed by normalizing net twist by the distance from apex to mitral valve plane. DMD patients exhibited normal left ventricular volumes and ejection fractions but manifested reduced midventricular and basal cross-sectional global circumferential strain compared with the reference group ( P &lt;0.005). These alterations also appeared in segmental analyses in the septal, anterior, lateral, and inferior walls ( P &lt;0.05). Conclusions— In patients predisposed to cardiomyopathies because of dystrophinopathy, occult regional cardiac dysfunction can be diagnosed with CMR tagging. This method of strain imaging analysis may offer a sensitive approach for delineating the presence and progression of cardiovascular disease and for assessing therapies designed to modulate the onset and course of heart failure.
THE INFLUENCE OF THYROIDECTOMY, GONADECTOMY, SUPRARENALECTOMY, AND SPLENECTOMY ON THE THYMUS GLAND OF RABBITS
Authors: David Marine, O. T. Manley, Emil J. Baumann
Journal: The Journal of Experimental Medicine (1924)

Thyroidectomy hastens, while gonadectomy delays, but does not permanently prevent, involution of the thymus. Suprarenalectomy alone not only delays involution of the thymus and lymphoid tissue but may cause their regeneration. Thyroidectomy prevents this reaction even after combined suprarenalectomy and gonadectomy. Suprarenalectomy plus gonadectomy is a more powerful stimulus for thymus and lymphoid regeneration than either of these influences alone. The combined effect of these two factors results in certain lymphoid and thymus hyperplasia in rabbits which persists until regeneration of accessory interrenal tissue corrects the physiological defect. The syndrome thus experimentally produced resembles status lymphaticus and is believed to depend mainly on a partial loss of certain functions of the interrenal and sex glands rather than of the chromaffin tissue. The normal and abnormal lymphoid and thymic hyperplasias of infancy and childhood are believed to be manifestations of a functional underdevelopment of the interrenal and sex glands of varying intensity. The so called lymphatic constitution which underlies or accompanies exophthalmic goiter, Addison's disease, and acromegaly also appears to be dependent on a partial suppression of certain functions of the interrenal and sex glands.