tbuckley/cabot-search huggingface dataset:
Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo.
Authors: K Inaba, M Inaba, M Naito, R M Steinman
Journal: The Journal of Experimental Medicine (1993)

Dendritic cells, while effective in sensitizing T cells to several different antigens, show little or no phagocytic activity. To the extent that endocytosis is required for antigen processing and presentation, it is not evident how dendritic cells would present particle-associated peptides. Evidence has now been obtained showing that progenitors to dendritic cells can internalize particles, including Bacillus Calmette-Guerin (BCG) mycobacteria. The particulates are applied for 20 h to bone marrow cultures that have been stimulated with granulocyte/macrophage colony-stimulating factor (GM-CSF) to induce aggregates of growing dendritic cells. Cells within these aggregates are clearly phagocytic. If the developing cultures are exposed to particles, washed, and "chased" for 2 d, the number of major histocompatibility complex class II-rich dendritic cells increases substantially and at least 50% contain internalized mycobacteria or latex particles. The mycobacteria-laden, newly developed dendritic cells are much more potent in presenting antigens to primed T cells than corresponding cultures of mature dendritic cells that are exposed to a pulse of organisms. A similar situation exists when the BCG-charged dendritic cells are injected into the footpad or blood stream of naive mice. Those dendritic cells that have phagocytosed organisms induce the strongest T cell responses to mycobacterial antigens in draining lymph node and spleen. The administration of antigens to GM-CSF-induced, developing dendritic cells (by increasing both antigen uptake and cell numbers) will facilitate the use of these antigen-presenting cells for active immunization in situ.
Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice
Authors: Hiroaki Okuyama, Hajime Nakamura, Yasuyuki Shimahara, Naoki Uyama, Yong-Won Kwon, Norifumi Kawada, Yoshio Yamaoka, Junji Yodoi
Journal: Journal of Hepatology (2004)
Dietary Induction of Colonic Tumors in a Mouse Model of Sporadic Colon Cancer
Authors: Kan Yang, Naoto Kurihara, Kunhua Fan, Harold Newmark, Basil Rigas, Laura Bancroft, Georgia Corner, Elayne Livote, Martin Lesser, Winfried Edelmann, Anna Velcich, Martin Lipkin, Leonard Augenlicht
Journal: Cancer Research (2008)

Abstract A defined rodent “new Western diet” (NWD), which recapitulates intake levels of nutrients that are major dietary risk factors for human colon cancer, induced colonic tumors when fed to wild-type C57Bl/6 mice for 1.5 to 2 years from age 6 weeks (two-thirds of their life span). Colonic tumors were prevented by elevating dietary calcium and vitamin D3 to levels comparable with upper levels consumed by humans, but tumorigenesis was not altered by similarly increasing folate, choline, methionine, or fiber, each of which was also at the lower levels in the NWD that are associated with risk for colon cancer. The NWD significantly altered profiles of gene expression in the flat colonic mucosa that exhibited heterogeneity among the mice, but unsupervised clustering of the data and novel statistical analyses showed reprogramming of colonic epithelial cells in the flat mucosa by the NWD was similar to that initiated by inheritance of a mutant Apc allele. The NWD also caused general down-regulation of genes encoding enzymes involved in lipid metabolism and the tricarboxylic acid cycle in colonic epithelial cells before tumor formation, which was prevented by the supplementation of the NWD with calcium and vitamin D3 that prevented colon tumor development, demonstrating profound interaction among nutrients. This mouse model of dietary induction of colon cancer recapitulates levels and length of exposure to nutrients linked to relative risk for human sporadic colon cancer, which represents the etiology of &amp;gt;90% of colon cancer in the United States and other Western countries. [Cancer Res 2008;68(19):7803–10]
Hypermutation is observed only in antibody H chain V region transgenes that have recombined with endogenous immunoglobulin H DNA: implications for the location of cis-acting elements required for somatic mutation.
Authors: A M Giusti, T Manser
Journal: The Journal of Experimental Medicine (1993)

Mice with transgenes containing an antibody H chain V region (VHDJH) gene were used in an analysis of the cis-acting elements required for hypermutation of immunoglobulin (Ig) V genes. These transgenes can somatically recombine with endogenous IgH DNA, leading to the formation of functional heavy (H) chains partially encoded by the transgenic VHDJH. The transgenomes in the five different lines of mice analyzed contain as little as 150 bp, and as much as 2.8 kb of natural DNA flanking the 5' side of the VH and either 1.5 or 2.3 kb (including the intronic enhancer and 5' matrix attachment region [MAR]) flanking the 3' side of VH. Hybridomas were constructed from immunized transgenic mice, and transgenes present in these hybridomas that had or had not recombined to form functional H chain loci were sequenced. The data obtained show that: (a) the recombined transgenes contain hypermutated VH genes; and (b) among such transgenes, even those containing only 150 bp of natural VH 5' flanking sequence and several kilobases of 5' plasmid vector sequence display a frequency, distribution, and type of mutation characteristic of conventional IgH loci. The data also indicate that transgenic VHDJH genes that have not recombined with endogenous IgH DNA are not substrates for hypermutation, even if they are flanked by 2.8 kb of natural 5' DNA, and 2.3 kb of natural 3' DNA, including the JH2-JH4 region, a MAR, and the intronic enhancer. Collectively, the data suggest that sequences 5' of the VH promoter are dispensable, a VH promoter and the intronic IgH enhancer region are not sufficient, and a region(s) within or 3' of the IgH constant region locus is requisite, for hypermutation of Ig VH transgenes.
Correlation Between Natural and Antibody-Dependent Cell-Mediated Cytotoxicity Against Tumor Targets in the Mouse. II. Characterization of the Effector Cells
Authors: A Santoni, R B Herberman, H T Holden
Journal: JNCI Journal of the National Cancer Institute (1979)

Direct comparison of the effector cells mediating natural killer (NK) activity against mouse tumor cells and antibody-dependent cell-mediated cytotoxicity (ADCC) against mouse tumor target cells coated with alloantisera Indicated that NK cells and K-cells (effector cells mediating ADCC) may belong to the same subpopulatlon of lymphocytes, but they have a different mechanism of killing. Effector cells mediating NK activity and ADCC were nonadherent, nonphagocytic Fc receptor-bearing cells that sediment at 3.5–4.5 mm/hour. Treatment with anti-Thy 1.2 serum in the absence of complement resulted In an Increase of NK activity, whereas this treatment caused a substantial loss in ADCC. Both NK activity and ADCC were equally sensitive to the In vivo or in vitro effects of X-irradiatlon. In vivo inoculations of high doses of hydrocortisone resulted in a reduction of NK activity, but ADCC was not affected. NK cells were trypsln-sensitlve, with a profound decrease in the cytolytic activity being observed in a 4-hour51Cr release assay. The activity, however, could be recovered after overnight incubation at 37° C. Trypsin treatment did not Inhibit ADCC as measured by the 18-hour assay.
Safety and Efficacy of Atacicept in Combination With Rituximab for Reducing the Signs and Symptoms of Rheumatoid Arthritis: A Phase II, Randomized, Double‐Blind, Placebo‐Controlled Pilot Trial
Authors: R. F. van Vollenhoven, S. Wax, Y. Li, P. P. Tak
Journal: Arthritis & Rheumatology (2015)

To explore the safety and tolerability of atacicept in combination with rituximab in patients with active rheumatoid arthritis (RA) receiving rituximab re-treatment.In this randomized, double-blind, placebo-controlled pilot trial, 2 infusions (1,000 mg per infusion) of intravenous rituximab, given 2 weeks apart, were followed by once-weekly subcutaneous injections of 150 mg atacicept or placebo for 25 weeks. Primary end points were the nature, incidence, and severity of adverse events (AEs). Secondary end points were the effects on peripheral blood B cells, disease activity biomarkers, and American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) response rates.Eighteen patients were randomized to receive atacicept and 9 to receive placebo. AEs occurred in 17 atacicept-treated patients (94.4%) and in all 9 placebo-treated patients (100%). There were no infection-related serious adverse events. Hypersensitivity and injection site reactions were more common, and more patients withdrew due to AEs, in the atacicept group. Median reductions in Ig levels from baseline to week 32 were greater with atacicept (median change in IgG -31.2%, IgM -60.9%, and IgA -56.4%) than with placebo (median change in IgG -4.4%, IgM -15.9%, and IgA -8.2%). Peripheral B cell numbers remained low in all patients after rituximab-mediated B cell depletion, limiting comparison of time to recovery between treatment groups. There were no between-group differences in ACR20, ACR50, and ACR70 response rates.In this exploratory trial, atacicept in combination with rituximab showed no new safety issues. Peripheral B cell counts remained too low to determine whether atacicept delayed B cell re-expansion following rituximab-mediated depletion. Despite clear biologic effects, adding atacicept to rituximab in patients with active RA was not associated with clinical benefit.
Serum adipocyte-fatty acid binding protein level is elevated in severe OSA and correlates with insulin resistance
Authors: D. C-L. Lam, A. Xu, K. S-L. Lam, B. Lam, J. C-M. Lam, M. M-S. Lui, M. S-M. Ip
Journal: European Respiratory Journal (2009)

Obstructive sleep apnoea (OSA) is associated with insulin resistance and metabolic syndrome. There is evidence that adipocyte-fatty acid binding protein (A-FABP) may be involved in the development of cardiometabolic dysfunction. The present authors hypothesise that A-FABP is upregulated in OSA. A total of 124 males without hypertension, diabetes mellitus, hyperlipidaemia or cardiovascular disease were recruited and underwent polysomnography. Serum A-FABP levels showed significant positive correlations with duration of oxygen desaturation and minimal oxygen saturation, fasting insulin and insulin resistance index by homeostasis model assessment. When subjects were divided into tertiles according to apnoea/hypopnoea index (AHI), serum A-FABP levels were significantly higher in the group with AHI ≥34.4 events·h −1 than the groups with AHI 13.2–34.4 events·h −1 or with AHI &lt;13.2 events·h −1 . Serum A-FABP levels were significantly higher in the AHI ≥34.4 group than obesity-matched subjects with AHI &lt;34.4 events·h −1 . Serum adipocyte-fatty acid binding protein levels correlated with obstructive sleep apnoea and insulin resistance, independently of obesity, and were significantly higher in severe obstructive sleep apnoea. Adipocyte-fatty acid binding protein may play a role in obstructive sleep apnoea and metabolic dysfunction.
Phase I Study of Docetaxel in Combination with the P-Glycoprotein Inhibitor, Zosuquidar, in Resistant Malignancies
Authors: Paula M. Fracasso, Lori J. Goldstein, Dinesh P. de Alwis, Janet S. Rader, Matthew A. Arquette, Sherry A. Goodner, Lisa P. Wright, Carole L. Fears, Robert J. Gazak, Valerie A. M. Andre, Michael F. Burgess, Christopher A. Slapak, Jan H. M. Schellens
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To determine the maximum tolerated dose, dose-limiting toxicity, and pharmacokinetics of docetaxel infused over 1 hour when given in combination with oral zosuquidar to patients with resistant solid tumors. Experimental Design: In cycle 1, patients received docetaxel alone. In subsequent cycles, zosuquidar was administered with docetaxel, which was escalated from 75 to 100 mg/m2. Zosuquidar was escalated from 100 to 300 mg/m2 every 8 hours on days 1 to 3 for a total of 7 doses, or from 400 to 500 mg every 12 hours for 2 doses administered 2 hours before docetaxel. The pharmacokinetics of docetaxel with and without zosuquidar administration were obtained. Results: Thirty-six of 41 patients completed at least one cycle of docetaxel and zosuquidar. The maximum tolerated dose was docetaxel 100 mg/m2 and zosuquidar 500 mg every 12 hours for 2 doses. The most common toxicity was neutropenia. In 35 patients, zosuquidar produced minimal increases in the docetaxel peak plasma concentrations and area under the curve. Dosing over 3 days with zosuquidar (7 doses) did not show benefit over the 1-day dosing. Of the 36 patients, one patient had a partial response, and 14 patients had disease stabilization. Conclusions: Docetaxel at 75 or 100 mg/m2 and zosuquidar 500 mg 2 hours before docetaxel and 12 hours later is well tolerated. Zosuquidar minimally alters the pharmacokinetics of docetaxel, allowing full dose docetaxel to be given with this P-glycoprotein modulator. A Phase II study with this combination in advanced breast carcinoma is underway.
Short-term Associations between Ambient Air Pollutants and Pediatric Asthma Emergency Department Visits
Authors: Matthew J. Strickland, Lyndsey A. Darrow, Mitchel Klein, W. Dana Flanders, Jeremy A. Sarnat, Lance A. Waller, Stefanie E. Sarnat, James A. Mulholland, Paige E. Tolbert
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Certain outdoor air pollutants cause asthma exacerbations in children. To advance understanding of these relationships, further characterization of the dose-response and pollutant lag effects are needed, as are investigations of pollutant species beyond the commonly measured criteria pollutants.Investigate short-term associations between ambient air pollutant concentrations and emergency department visits for pediatric asthma.Daily counts of emergency department visits for asthma or wheeze among children aged 5 to 17 years were collected from 41 Metropolitan Atlanta hospitals during 1993-2004 (n = 91,386 visits). Ambient concentrations of gaseous pollutants and speciated particulate matter were available from stationary monitors during this time period. Rate ratios for the warm season (May to October) and cold season (November to April) were estimated using Poisson generalized linear models in the framework of a case-crossover analysis.Both ozone and primary pollutants from traffic sources were associated with emergency department visits for asthma or wheeze; evidence for independent effects of ozone and primary pollutants from traffic sources were observed in multipollutant models. These associations tended to be of the highest magnitude for concentrations on the day of the emergency department visit and were present at relatively low ambient concentrations.Even at relatively low ambient concentrations, ozone and primary pollutants from traffic sources independently contributed to the burden of emergency department visits for pediatric asthma.
Cardiovascular Outcome Studies With Novel Antidiabetes Agents: Scientific and Operational Considerations
Authors: Boaz Hirshberg, Arie Katz
Journal: Diabetes Care (2013)

The requirement from several health authorities to demonstrate cardiovascular (CV) safety of new antidiabetes drugs represents both an opportunity and a challenge. In a few years, this requirement may avail to regulatory agencies and the medical community data from large, prospective clinical trials assessing the benefits and risks of such drugs in high–CV risk patients with diabetes. These studies may also provide an opportunity to assess safety signals beyond CV. However, these studies pose significant challenges, including study design, long-term retention of patients, the risk of missing data, and varying regulatory requirements among countries and regions. In addition, these trials cost hundreds of millions of dollars. This significant investment may potentially detract from the investigation of other drug-specific risks or benefits. In this article, we discuss considerations in the design and execution of CV outcome studies in diabetes.

The goals of antidiabetes treatment are to avert the untoward metabolic effects of high glucose concentrations and prevent microvascular and macrovascular complications. Compelling data in type 2 diabetic patients support the conclusion that improved long-term glycemic control reduces the risk of microvascular complications (1–3). Based on several large outcome studies, including the seminal Diabetes Control and Complications Trial (DCCT) and UK Prospective Diabetes Study (UKPDS), HbA1c was established as a surrogate biomarker of glycemic control and therapeutic goals were set accordingly (4).

Based on the proven correlation between HbA1c and microvascular complications and inconclusive data on CV benefits, most clinical development programs for antidiabetes drugs have focused on glucose lowering. While confirmatory studies in these clinical development programs were being conducted to establish the glucose-lowering properties of novel drugs, CV safety assessment has been limited. CV safety concerns have been raised with respect to several antidiabetes compounds approved or under development for the treatment of type 2 …
Methicillin-resistant Staphylococcus aureus in intensive care units
Authors: S. Kochhar
Journal: Journal of the Royal Society of Medicine (2005)

Dr McNaught is right to point out examples of racism in the NHS (December 2004 JRSM 1 ).But what to do about it?Maybe we can learn some lessons from the past.Today there is an over-representation of black people in the mental health system but in the 1960s Irish people were over-represented. 2 Psychiatrists thought that the prevalence of schizophrenia was high in people from the west of Ireland and invented a new syndrome 'western seaboard psychosis'. 3 Anthropologists descended on the unsuspecting immigrants to ask them if their Catholic faith caused their minds to unbalance and psychiatrists followed to dole out antipsychotics.But then some proper research was done and it showed no excess of schizophrenia in Irish immigrants. 4 The methods of case collection in the early studies were poor and cross-cultural comparisons were not properly thought through. 3 Today Irish people are no more likely to be diagnosed with schizophrenia than anyone else.How did this happen?I would love to say that it was because of the new research or because of government initiatives.The research helped a bit but the main cures for anti-Irish discrimination were that the new immigrants were richer, better educated, better informed and more questioning.They would not be fobbed off with a misdiagnosis.An increasing understanding and appreciation of Irish culture also helped reduce anti-Irish discrimination generally.The most effective cure of all was time.A cynic would add that, nowadays, people have a new batch of immigrants (such as asylum seekers) to discriminate against.So we need fewer new policy drives and more changes of heart.These will only come from changes in society.Blaming individuals or even the NHS will not help.
EULAR recommendations for vaccination in paediatric patients with rheumatic diseases
Authors: M W Heijstek, L M Ott de Bruin, M Bijl, R Borrow, F van der Klis, I Koné-Paut, A Fasth, K Minden, A Ravelli, M Abinun, G S Pileggi, M Borte, N M Wulffraat
Journal: Annals of the Rheumatic Diseases (2011)

Evidence-based recommendations for vaccination of paediatric patients with rheumatic diseases (PaedRD) were developed by following the EULAR standardised procedures for guideline development. The EULAR task force consisted of (paediatric) rheumatologists/immunologists, one expert in vaccine evaluation, one expert in public health and infectious disease control, and one epidemiologist. A systematic literature review was conducted in MEDLINE, EMBASE, and abstracts of the EULAR and American College of Rheumatology meetings of 2008/9. The level of evidence and strength of recommendation were based on customary scoring systems. Delphi voting was applied to assess the level of agreement between task force members. 107 papers and eight abstracts were used. The majority of papers considered seasonal influenza (41) or pneumococcal (23) vaccination. 26 studies were performed specifically in paediatric patients, and the majority in adult rheumatoid arthritis and systemic lupus erythematosus patients. Fifteen recommendations were developed with an overall agreement of 91.7%. More research is needed on the safety and immunogenicity of (live-attenuated) vaccination in PaedRD, particularly in those using biologicals, and the effect of vaccination on prevention of infections.
Evaluation of the effectiveness of cyclical and constant current on sweat volume and stimulation for cystic fibroses diagnoses
Authors: Carla Gomez, Maria Servidoni, Fernando Marson, Paulo Canavezi, Adriana Vinagre, Célia Pavan, Michelle Santos-Rodon, Eduardo Costa, Antonio Ribeiro, Maria Ribeiro, Francisco Vieira Junior, Gabriel Hessel, Carlos Levy, Carmen Bertuzzo, Sonia Lorena, Jose Ribeiro
Journal: European Respiratory Journal (2014)

Objective:  Analyze and compare different electrical currents and frequencies for stimulation and production of sweat using equipment of iontoforesis. Methods:  An experimental, randomized study using an equipment of iontophoresis with pilocarpine conducted by the University Center of Biomedical Engineering. 48 healthy subjects were tested, all above 18 years old, using currents of 0.5 to 1.5 mA, frequency between 0 to 5.000 Hertz, sweat stimulation time of 10 minutes and collecting time of 30 minutes. The weight of sweat was measured, the impedance of electrode-skin combination and the subject discomfort during the exam. Results:  The sweat weight was influenced on different currents (p= 0.0005) and frequencies (p=0.0088). The impedance was induced, also, on different currents (p=0.0007) and frequencies (0.0003). However there wasn9t any result of the interaction between the different currents and frequencies on the sweat volume and the impedance (p >0.74). Also there wasn9t any statistical difference on the discomfort during the tests. Conclusion:  The used electrical currents and frequencies were minor than those used in an ordinary sweat test and allowed effective stimulation and collecting of sweat, without collateral effects. Theses currents and frequencies constitute a promising method for the stimulation and the collecting of sweat on patients with Cystic Fibrosis. STSG: Sweat test study group.
THE CLINICAL SIGNIFICANCE OF THE RORSCHACH TEST
Authors: C. EARLE JOHNSON, JAMES E. SHERMAN
Journal: American Journal of Psychiatry (1948)

It will be noticed that the authors have not laid overemphasis on sexual responses. These are manifested by particular attention to the lower details, interpreted as portions of the female pelvis or to phallic symbols or to their complete avoidance (sexual repression). This is because they occur generally in behavior problems and correctly belong in the realm of clinical psychology. Repressed sexual responses are occasionally encountered in the manic type of manic-depressive psychosis (particularly when the patient is recovering and is unsure of himself) and more rarely in psychoneuroses. Likewise, we have not attempted to interpret the degree of mental defect because this can be ascertained only by a psychometric test and not by the Rorschach. We do believe from our findings that the Rorschach test can be of tremendous value in psychiatry but, as previously stated, should be nothing more than a useful aid to the psychiatrist in his diagnostic investigations.