tbuckley/cabot-search huggingface dataset:
Redirecting Gene-Modified T Cells toward Various Cancer Types Using Tagged Antibodies
Authors: Koji Tamada, Degui Geng, Yukimi Sakoda, Navneeta Bansal, Ratika Srivastava, Zhaoyang Li, Eduardo Davila
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To develop an adaptable gene-based vector that will confer immune cell specificity to various cancer types. Experimental Design: Human and mouse T cells were genetically engineered to express a chimeric antigen receptor (CAR) that binds a fluorescein isothiocyanate (FITC) molecule, termed anti-FITC CAR T cells. Various antibodies (Ab) currently in clinical use including cetuximab (Ctx), trastuzumab (Her2), and rituximab (Rtx) were conjugated with FITC and tested for their ability to bind tumor cells, activate T cells, and induce antitumor effects in vitro and in vivo. Results: Anti-FITC CAR T cells recognize various cancer types when bound with FITC-labeled Abs resulting in efficient target lysis, T-cell proliferation, and cytokine/chemokine production. The treatment of immunocompromised mice with human anti-FITC CAR T cells plus FITC-labeled cetuximab (FITC-Ctx) delayed the growth of colon cancer but unexpectedly led to the outgrowth of EGF receptor (EGFR)-negative tumor cells. On the other hand, in a human pancreatic cancer cell line with uniform EGFR expression, anti-FITC CAR T cells plus FITC-Ctx eradicated preestablished late-stage tumors. In immunocompetent mice, anti-FITC CAR T cells exhibited potent antitumor activity against syngeneic mouse breast cancer expressing Her2 and B-cell lymphoma expressing CD20 by combining with FITC-Her2 and FITC-Rtx, respectively. In addition, the activity of anti-FITC CAR T cells could be attenuated by subsequent injections of nonspecific FITC-IgG. Conclusion: These studies highlight an applicability of anti-tag CAR technology to treat patients with different types of cancers and a possibility to regulate CAR T-cell functions with competing FITC molecules. Clin Cancer Res; 18(23); 6436–45. ©2012 AACR.
A Multistate Outbreak of Escherichia coli O157:H7—Associated Bloody Diarrhea and Hemolytic Uremic Syndrome From Hamburgers
Authors: B P Bell, M Goldoft, P M Griffin, M A Davis, D C Gordon, P I Tarr, C A Bartleson, J H Lewis, T J Barrett, J G Wells
Journal: JAMA (1994)

To determine the source of and describe a large outbreak of Escherichia coli O157:H7 infections in Washington State.Case-control study; environmental investigation; provider-based surveillance for E coli O157:H7 infections.Chain of fast-food restaurants, hospitals, physician offices, local laboratories, and local health departments.Patients with diarrhea and neighborhood controls. A case was defined as diarrhea with culture-confirmed E coli O157:H7 infection or postdiarrheal hemolytic uremic syndrome (HUS) occurring from December 1, 1992, through February 28, 1993, in a Washington State resident. Controls were age- and neighborhood-matched friends of the first 16 case patients.Announcement to the public; recall of implicated hamburger lots.Abatement of outbreak due to E coli O157:H7.Infection was associated with eating at a fast-food chain (chain A) in the 10 days before symptoms began. Twelve (75%) of 16 case patients but no controls had eaten at chain A (matched odds ratio undefined; lower 95% confidence interval, 3.5; P < .001). In total, 501 cases were reported, including 151 hospitalizations (31%), 45 cases of HUS (9%), and three deaths. Forty-eight patients (10%) had secondary infections. Of the remaining 453 patients (90%), 398 (86%) reported eating at a Washington chain A restaurant; 92% of them reported eating a regular hamburger. The pulsed-field gel electrophoresis pattern of the E coli O157:H7 strains isolated from all regular hamburger lots of a single production date shipped to Washington was identical to that of the strains isolated from patients. Ten (63%) of 16 regular hamburgers cooked according to chain A policy had internal temperatures below 60 degrees C. Public health action removed more than 250,000 potentially contaminated hamburgers, preventing an estimated 800 cases.This E coli O157:H7 outbreak, the largest reported, resulted from errors in meat processing and cooking. Public health surveillance through state-mandated reporting of E coli O157:H7 infection as is carried out in Washington State was critical for prompt outbreak recognition and control. Measures should be developed to reduce meat contamination. Consumers and food service workers should be educated about cooking hamburger meat thoroughly.
The control effect of histamine on body temperature and respiratory function in IgE-dependent systemic anaphylaxis
Authors: Yoko Makabe-Kobayashi, Yoshio Hori, Tetsuya Adachi, Satsuki Ishigaki-Suzuki, Yoshihiro Kikuchi, Yutaka Kagaya, Kunio Shirato, András Nagy, Azusa Ujike, Toshiyuki Takai, Takehiko Watanabe, Hiroshi Ohtsu
Journal: Journal of Allergy and Clinical Immunology (2002)
ABC of Work Related Disorders: STRESS AT WORK
Authors: J. von Onciul
Journal: BMJ (1996)

General adaptation syndrome 1 Alarm reaction 2 Resistance stage 3 Exhaustion stageChanges in the work environment have led to a change in the balance between physical and mental activity.Technological developments have reduced the amount of heavy physical work.Mental and emotional strain have increased in new working environments that are characterised by lack of time, more uncontrollable factors, background distractions, lack of space, general uncertainty, and more administrative work.The general adaptation syndrome, described by the physiologist Selye in 1975, characterises the process of prolonged exposure to stress and is a useful staged concept. Work related stressors
Chronic Rhinosinusitis (crs) in Primary Immunodeficient Patients
Authors: A.B.F. Fomin, E.B. Farah, M.S. Nascimento, A.B.M. Castro, A.C. Pastorino, E.M.G. Carnide, C.M.A. Jacob, L.A.N. Oliveira
Journal: Journal of Allergy and Clinical Immunology (2006)
Sepsis and mechanisms of inflammatory response: is exercise a good model?
Authors: R J Shephard
Journal: British Journal of Sports Medicine (2001)

Objectives —The immune changes induced by a bout of prolonged and vigorous exercise have been suggested to be a useful experimental model of sepsis and the inflammatory response. Available literature was reviewed to evaluate this hypothesis. Methods —Literature describing the immune response to various patterns of exercise was compared with data on the immune changes observed during sepsis and inflammation. Results —Although there are qualitative similarities between the immune responses to exercise and sepsis, the magnitude of the changes induced by most forms of exercise remains much smaller than in a typical inflammatory response. Indeed, the exercise induced changes in some key elements such as plasma cytokine concentrations are too small to be detected reliably by current technology. Conclusions —If exercise is to provide a valid model of sepsis and the inflammatory response, it will be necessary to focus on subjects who are willing to exercise extremely hard, to use the pattern of exercise that has the greatest effect on the immune system, and to combine this stimulus with other psychological, environmental, or nutritional stressors.
An Antibody Which Precipitates Dane Particles in Acute Hepatitis Type B: Relation to Receptor Sites Which Bind Polymerized Human Serum Albumin on Virus Particles
Authors: A. Alberti, P. Pontisso, E. Schiavon, G. Realdi
Journal: Hepatology (1984)

An antibody, which is distinct from the HBsAg, and reacts with antigenic sites on Dane particles HBcAg and HBeAg, was studied by radioimmunoprecipitation of radioactive intact hepatitis B virions in sera obtained early in the course of acute hepatitis type B. The antibody, previously termed anti-Dane particle (anti-DP) antibody, was reactive with Dane particles and HBsAg particles obtained from HBeAg-positive sera but not with HBsAg particles from anti-HBe containing sera. The expression on virus particles of the evoking antigen correlated with levels of binding sites for polymerized human serum albumin (pHSA) as detected by solid-phase radioimmunoassay. In acute hepatitis B sera, levels of anti-DP antibody activity showed inverse correlation with expression of pHSA receptors on circulating virus particles, although the two reactivities were not mutually exclusive. In inhibition experiments, pHSA blocked precipitation of Dane particles by anti-DP positive sera, while native human albumin and polymerized bovine albumin had no effect. The inhibition by pHSA of the anti-DP reaction appeared specific since identical concentrations of pHSA did not interfere with precipitation of virus particles by anti-HBs. Affinity chromatography studies with anti-DP insolubilized on Sepharose 4B columns showed selective binding to the gel of radioactive Dane particles; 125 I-HBsAg was not reactive. The binding of Dane particles to anti-DP columns was completely inhibited when virus particles were applied to the gel in pHSA; pretreat-ment of the column with pHSA did not affect the reaction. These results and the demonstration that anti-DP positive sera were free of anti-pHSA antibodies indicate that anti-DP reacts with antigenic determinants on Dane particles that are involved in or by pHSA binding sites. Anti-DP positive sera and IgG fractions inhibited expression of pHSA receptors on purified virus particles. Our findings support suggestions that the anti-DP response may be relevant to the phase of virus neutralization, on the basis of the hypothesis that the virus receptor for pHSA could play a role in mediating virus access to hepatocytes which may have similar albumin receptors on their membrane.
Effects of low-sodium diet and spironolactone on portal pressure in patients with compensated cirrhosis
Authors: Juan Carlos García-Pagán, Juan Manuel Salmerón, Faust Feu, Angelo Luca, Pere Ginés, Pilar Pizcueta, Juan Claria, Carlos Piera, Vicente Arroyo, Jaume Bosch, Juan Rodés
Journal: Hepatology (1994)

The aim of this study was to investigate the hemodynamic effects of spironolactone associated with a low-sodium diet (n=14) or a low-sodium diet alone (n=9) in patients with compensated cirrhosis and portal hypertension. Spironolactone significantly reduced the plasma volume. This effect was associated with a significant reduction in the hepatic venous pressure gradient, from 17.6 ± 3.6 mm Hg to 15.3 ± 3.5 mm Hg (−13% ± 13%; p&lt;0.01). Azygos blood flow (−20% ± 20%), cardiac output (−16.2% ± 10.5%) and mean arterial pressure (−9% ± 9%) also decreased significantly. However, there were no significant changes in hepatic blood flow. Patients receiving low-sodium diet alone experienced a mild but significant reduction in hepatic venous pressure gradient (−6.3% ± 6%) and in mean arterial pressure (−4% ± 5%). There were no significant changes in cardiac output and in hepatic or azygos blood flows. This study indicates that low-sodium diet plus administration of spironolactone reduces portal pressure and azygos blood flow in patients with compensated cirrhosis. Low-sodium diet alone only produces mild effects that are likely to be clinically irrelevant. (Hepatology 1994;19:1095-1099.)
Dominant Role of Oncogene Dosage and Absence of Tumor Suppressor Activity in <i>Nras-</i>Driven Hematopoietic Transformation
Authors: Jin Xu, Kevin M. Haigis, Ari J. Firestone, Megan E. McNerney, Qing Li, Elizabeth Davis, Shann-Ching Chen, Joy Nakitandwe, James Downing, Tyler Jacks, Michelle M. Le Beau, Kevin Shannon
Journal: Cancer Discovery (2013)

Biochemical properties of Ras oncoproteins and their transforming ability strongly support a dominant mechanism of action in tumorigenesis. However, genetic studies unexpectedly suggested that wild-type (WT) Ras exerts tumor suppressor activity. Expressing oncogenic Nras(G12D) in the hematopoietic compartment of mice induces an aggressive myeloproliferative neoplasm that is exacerbated in homozygous mutant animals. Here, we show that increased Nras(G12D) gene dosage, but not inactivation of WT Nras, underlies the aggressive in vivo behavior of Nras(G12D/G12D) hematopoietic cells. Modulating Nras(G12D) dosage had discrete effects on myeloid progenitor growth, signal transduction, and sensitivity to MAP-ERK kinase (MEK) inhibition. Furthermore, enforced WT N-Ras expression neither suppressed the growth of Nras-mutant cells nor inhibited myeloid transformation by exogenous Nras(G12D). Importantly, NRAS expression increased in human cancer cell lines with NRAS mutations. These data have therapeutic implications and support reconsidering the proposed tumor suppressor activity of WT Ras in other cancers.Understanding the mechanisms of Ras -induced transformation and adaptive cellular responses is fundamental. The observation that oncogenic Nras lacks tumor suppressor activity, whereas increased dosage strongly modulates cell growth and alters sensitivity to MEK inhibition, suggests new therapeutic opportunities in cancer.
Serous Tubal Intraepithelial Carcinoma: Its Potential Role in Primary Peritoneal Serous Carcinoma and Serous Cancer Prevention
Authors: Joseph W. Carlson, Alexander Miron, Elke A. Jarboe, Mana M. Parast, Michelle S. Hirsch, Yonghee Lee, Michael G. Muto, David Kindelberger, Christopher P. Crum
Journal: Journal of Clinical Oncology (2008)

A diagnosis of primary peritoneal serous carcinoma (PPSC) requires exclusion of a source in other reproductive organs. Serous tubal intraepithelial carcinoma (STIC; stage 0) has been described in asymptomatic women with BRCA mutations and linked to a serous cancer precursor in the fimbria. This study examined the frequency of STIC in PPSC and its clinical outcome in BRCA-positive women.Presence or absence of STIC was recorded in consecutive cases meeting the 2001 WHO criteria for PPSC, including 26 patients with nonuniform sampling of the fallopian tubes (group 1) and 19 patients with complete tubal examination (group 2; sectioning and extensively examining the fimbriated end, or SEE-FIM protocol). In selected cases, STIC or its putative precursor and the peritoneal tumor were analyzed for p53 mutations (exons 1 to 11). Outcome of STIC was ascertained by literature review.Thirteen (50%) of 26 PPSCs in group 1 involved the endosalpinx, with nine STICs (35%). Fifteen (79%) of 19 cases in group 2 contained endosalpingeal involvement, with nine STICs (47%). STIC was typically fimbrial and unifocal, with variable invasion of the tubal wall. In five of five cases, the peritoneal and tubal lesion shared an identical p53 mutation. Of 10 reported STICs in BRCA-positive women, all patients were without disease on follow-up.The fimbria is the source of nearly one half of PPSCs, suggesting serous malignancy originates in the tubal mucosa but grows preferentially at a remote peritoneal site. The generally low risk of recurrence in stage 0 (STIC) disease further underscores STIC as a possible target for early serous cancer detection and prevention.
Reproductive and genetic evidence for a reticulate evolutionary history of mass-spawning corals
Authors: M. Hatta, H. Fukami, W. Wang, M. Omori, K. Shimoike, T. Hayashibara, Y. Ina, T. Sugiyama
Journal: Molecular Biology and Evolution (1999)

Reef-building corals, which reproduce through simultaneous multispecies spawning, are thought to hybridize frequently, and it is hypothesized that they have evolved in repeated rounds of species separation and fusion. We conducted cross-fertilization experiments and molecular analyses with a number of mass-spawning coral species in the genus Acropora. A high rate of interspecific fertilization occurred between some species despite very different morphologies. The hybrid larvae developed normally and contained an allelic sequence transmitted from each parent, suggesting common diploid hybridization. Molecular phylogenetic analyses provided strong evidence for a gene pool shared between the hybridizing species. These reproductive and genetic characteristics are consistent with a species complex formed under the separation/fusion processes predicted for a reticulate evolutionary history.
Estimating Podocyte Number and Density Using a Single Histologic Section
Authors: Madhusudan Venkatareddy, Su Wang, Yan Yang, Sanjeevkumar Patel, Larysa Wickman, Ryuzoh Nishizono, Mahboob Chowdhury, Jeffrey Hodgin, Paul A. Wiggins, Roger C. Wiggins
Journal: Journal of the American Society of Nephrology (2013)

The reduction in podocyte density to levels below a threshold value drives glomerulosclerosis and progression to ESRD. However, technical demands prohibit high-throughput application of conventional morphometry for estimating podocyte density. We evaluated a method for estimating podocyte density using single paraffin-embedded formalin-fixed sections. Podocyte nuclei were imaged using indirect immunofluorescence detection of antibodies against Wilms' tumor-1 or transducin-like enhancer of split 4. To account for the large size of podocyte nuclei in relation to section thickness, we derived a correction factor given by the equation CF=1/(D/T+1), where T is the tissue section thickness and D is the mean caliper diameter of podocyte nuclei. Normal values for D were directly measured in thick tissue sections and in 3- to 5-μm sections using calibrated imaging software. D values were larger for human podocyte nuclei than for rat or mouse nuclei (P<0.01). In addition, D did not vary significantly between human kidney biopsies at the time of transplantation, 3-6 months after transplantation, or with podocyte depletion associated with transplant glomerulopathy. In rat models, D values also did not vary with podocyte depletion, but increased approximately 10% with old age and in postnephrectomy kidney hypertrophy. A spreadsheet with embedded formulas was created to facilitate individualized podocyte density estimation upon input of measured values. The correction factor method was validated by comparison with other methods, and provided data comparable with prior data for normal human kidney transplant donors. This method for estimating podocyte density is applicable to high-throughput laboratory and clinical use.
Pre-emption of human cell-mediated lympholysis by a suppressive mechanism activated in mixed lymphocyte cultures
Authors: PM Sondel, MW Jacobson, FH Bach
Journal: The Journal of Experimental Medicine (1975)

The regulation of B-cell and T-cell immune responses has been extensively examined and in the experimental animal appears to involve regulatory or suppressor T cells (1-4). The limitations of in vitro experimentation have made comparable study of nonpathological human suppression quite difficult (5). We report here an in vitro method that generates and quantitates suppressor activity in man after antigen-specific activation in mixed leukocyte culture (MLC). The one-way MLC induces both a proliferative response (6) and the generation of cytotoxic T lymphocytes (CTLs) (7). Both of these responses are mediated by antigen-specific T-cell subpopulations (8,9) and have been correlated with recognitive and destructive phases of allograft rejection. Recent reports have examined the antigen reactivity of mouse (10,11), rat (12), or human (13,14) lymphocytes obtained after proliferation in MLC. In all cases, after the primary MLC proliferative peak, the recovered lymphocytes rapidly differentiate upon re-exposure to the initial stimulating population, but do so only weakly when exposed to a presumably noncross-reactive third-party stimulating population. Velocity sedimentation separation studies have shown that the blast cells produced in a primary MLC revert to small lymphocytes that rapidly differentiate into proliferating and/or cytotoxic T lymphocytes upon restimulation with the initial antigen (15). These findings demonstrate that positive selection for the responding population in primary MLC does exist and may account for at least part of the specificity of the secondary response. However, this positive selection does not preclude possible involvement of a suppressor mechanism. In fact we have detected suppressor activity in primary MLC sensitization cultures at a time when the proliferation responsible for positive selection does not preclude possible involvement of a suppressor mechanism. In fact we have detected suppressor activity in primary MLC sensitization cultures at a time when the proliferation responsible for positive selection in not yet significant, suggesting that suppression may be overriding importance in the specificity of MLC-activated secondary responses.
Management of gastric cancer in Asia: resource-stratified guidelines
Authors: Lin Shen, Yan-Shen Shan, Huang-Ming Hu, Timothy J Price, Bhawna Sirohi, Kun-Huei Yeh, Yi-Hsin Yang, Takeshi Sano, Han-Kwang Yang, Xiaotian Zhang, Sook Ryun Park, Masashi Fujii, Yoon-Koo Kang, Li-Tzong Chen
Journal: The Lancet Oncology (2013)
Asthma control during long term treatment with regular inhaled salbutamol and salmeterol
Authors: D R. Taylor, G I. Town, G P. Herbison, D. Boothman-Burrell, E. M Flannery, B. Hancox, E. Harre, K. Laubscher, V. Linscott, C. M Ramsay, G. Richards
Journal: Thorax (1998)

<h3>BACKGROUND</h3> The adverse effects of long term treatment of asthma with the short acting β agonist fenoterol have been established in both epidemiological and clinical studies. A study was undertaken to investigate the efficacy and safety of long term treatment with salbutamol and salmeterol in patients with mild to moderate bronchial asthma. <h3>METHODS</h3> In a two centre double dummy crossover study 165 patients were randomly assigned to receive salbutamol 400 μg qid, salmeterol 50 μg bid, or placebo via a Diskhaler. All patients used salbutamol as required for symptom relief. The study comprised a four week run in and three treatment periods of 24 weeks, each of which was followed by a four week washout. Asthma control was assessed by measuring mean morning and evening peak expiratory flow rate (PEFR), a composite daily asthma score, and minor and major exacerbation rates. Washout assessments included methacholine challenge and bronchodilator dose response tests. Analysis was by intention to treat. <h3>RESULTS</h3> Data from 157 patients were analysed. Relative to placebo, the mean morning PEFR increased by 30 l/min (95% CI 26 to 35) for salmeterol but did not change for salbutamol. Evening PEFR increased by 25 l/min (95% CI 21 to 30) and 21 l/min (95% CI 17 to 26), respectively (p&lt;0.001). Salmeterol improved the asthma score compared to placebo (p&lt;0.001), but there was no overall difference with salbutamol. Only daytime symptoms were improved with salbutamol. The minor exacerbation rates were 0.29, 0.88, and 0.97 exacerbations/patient/year for salmeterol, salbutamol and placebo, respectively (p&lt;0.0001 for salmeterol). The corresponding major exacerbation rates were 0.22, 0.51 and 0.40, respectively (p&lt;0.03 for salmeterol). For salbutamol the asthma score deteriorated over time (p&lt;0.01), and the time spent in major exacerbation was significantly longer compared with placebo (12.3 days (95% CI 4.2 to 20.4)) versus 8.4 days (95% CI 5.2 to 11.6), p = 0.02). There was no evidence of rebound deterioration in asthma control, lung function, or bronchial hyperresponsiveness following cessation of either active treatment, and no evidence of tolerance to salbutamol or salmeterol. <h3>CONCLUSIONS</h3> Regular treatment with salmeterol is effective in controlling asthma symptoms and reduces minor more than major exacerbation rates. Salbutamol was associated with improved daytime symptoms but subtle deterioration in asthma control occurred over time. Salbutamol should therefore be used only as required.