tbuckley/cabot-search huggingface dataset:
Interleukin 5 messenger RNA expression by eosinophils in the intestinal mucosa of patients with coeliac disease.
Authors: P Desreumaux, A Janin, J F Colombel, L Prin, J Plumas, D Emilie, G Torpier, A Capron, M Capron
Journal: The Journal of Experimental Medicine (1992)

Interleukin 5 (IL-5), the major factor involved in eosinophil differentiation, is produced by T cells or mast cells. In the present study, we found that eosinophils infiltrating the mucosa of four patients with active coeliac disease also express the IL-5 mRNA. No positive signal was obtained in normal duodenum tissues and in the cell infiltrate from patients submitted to gluten restriction. The identification of labeled mucosal cells as eosinophils relied on their typical morphology. Moreover, highly purified blood eosinophils from three out of four patients with eosinophilia were also strongly labeled with the IL-5 antisense but not with the corresponding sense probe. Together, these results suggest that eosinophils have the capacity to synthesize IL-5, which could contribute to paracrine interactions with T and B cells and, in autocrine fashion, locally participate, through binding to the IL-5 receptor, to eosinophil differentiation and activation. These data might have implications not only in the pathology of coeliac disease but also in other diseases associated with eosinophil infiltration.
Agranlocytosis caused by ticlopindine and its mechanism
Authors: Kazutoshi Ono, Kazuhiro Kurohara, Masahiro Yoshihara, Yoshinori Shimamoto, Masaya Yamaguchi
Journal: American Journal of Hematology (1991)

Abstract A 75‐year‐old female patient with agranulocytosis caused by ticlopidine is reported. She took the drug at 200 mg/day for 30 days to prevent recurrence of cerebral infarction. The leukocyte count at the nadir was 500/μl on the 34th day since she started to take the drug. Complete recovery of her peripheral leukocytes came 12 days after its withdrawal. In this patient, mechanisms of ticlopidine‐caused agranulocytosis were studied. The lymphocyte stimulation test using ticlopidine was negative. In the culture of marrow cells depleted of lymphocytes, ticlopidine directly inhibited the CFU‐C in a dose‐dependent manner. Neither the serum on the day of admission nor the T‐lymphocytes pre‐cultured with ticlopidine had any effect on the CFU‐C. The lymphocyte stimulation test is useless in an attempt to find the causal drug in agranulocytosis if it is caused in a directly toxic manner. Agranulocytosis caused by ticlopidine is rare, but careful follow‐up is necessary in the case of patients on the drug because there are some whose marrow cells are very sensitive to it.
Targeting Proteasomal Protein Degradation in Cancer–Letter
Authors: William K.K. Wu
Journal: Clinical Cancer Research (2012)

In the recently published Molecular Pathways article ([1][1]), Molineaux summarized the recent progress in the development of proteasome inhibitors for the treatment of cancer. The author stated that inhibition of NF-κB is one of the major mechanisms mediating the antitumor effect of proteasome
Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells
Authors: Teru Hideshima, Laurence Catley, Hiroshi Yasui, Kenji Ishitsuka, Noopur Raje, Constantine Mitsiades, Klaus Podar, Nikhil C. Munshi, Dharminder Chauhan, Paul G. Richardson, Kenneth C. Anderson
Journal: Blood (2006)
Fasting Insulin and Outcome in Early-Stage Breast Cancer: Results of a Prospective Cohort Study
Authors: P. J. Goodwin
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Insulin, a member of a family of growth factors that includes insulin-like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via insulin and IGF-I receptors. Because of this and because of its recognized association with obesity, an adverse prognostic factor in breast cancer, we examined the prognostic associations of insulin in early-stage breast cancer. PATIENTS AND METHODS: A cohort of 512 women without known diabetes, who had early-stage (T1 to T3, N0 to N1, and M0) breast cancer, was assembled and observed prospectively. Information on traditional prognostic factors and body size was collected, and fasting blood was obtained. RESULTS: Fasting insulin was associated with distant recurrence and death; the hazard ratios and 95% confidence intervals (CI) for those in the highest (> 51.9 pmol/L) versus the lowest (< 27.0 pmol/L) insulin quartile were 2.0 (95% CI, 1.2 to 3.3) and 3.1 (95% CI, 1.7 to 5.7), respectively. There was some evidence to suggest that the association of insulin with breast cancer outcomes may be nonlinear. Insulin was correlated with body mass index (Spearman r = 0.59, P < .001), which, in turn, was associated with distant recurrence and death (P < .001). In multivariate analyses that included fasting insulin and available tumor- and treatment-related variables, adjusted hazard ratios for the upper versus lower insulin quartile were 2.1 (95% CI, 1.2 to 3.6) and 3.3 (95% CI, 1.5 to 7.0) for distant recurrence and death, respectively. CONCLUSION: Fasting insulin level is associated with outcome in women with early breast cancer. High levels of fasting insulin identify women with poor outcomes in whom more effective treatment strategies should be explored.
Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise
Authors: K W Rundell, B A Spiering, J M Baumann, T M Evans
Journal: British Journal of Sports Medicine (2005)

Background: Exercise induced bronchoconstriction (EIB) is common in elite athletes. Eucapnic voluntary hyperventilation (EVH) is a laboratory test recommended for the identification of EIB in athletes, secondary to a field exercise challenge. Montelukast attenuates EIB, but its protective effect against airway narrowing from EVH has not been investigated. Objective: To examine the effectiveness of montelukast after exercise and after EVH. Methods: A randomised, placebo controlled, double blind, crossover study was performed with 11 physically active EIB positive subjects (eight men, three women; mean (SD) age 22.8 (6.8) years). Six hours before each of the following challenges 10 mg montelukast or placebo was ingested: ( a ) a six minute, cold air (−3°C) maximal effort work accumulation cycle ergometer exercise; ( b ) EVH, breathing 5% CO 2 compressed air at 85% maximal voluntary ventilation for six minutes. Spirometry was performed before and 5, 10, and 15 minutes after the challenge. At least 48 hours was observed between challenges. Results: No differences in forced expiratory volume in one second (FEV 1 ) were found after the two challenges. Exercise and EVH resulted in falls in FEV 1 of 22.4 (18.0) and 25.6 (16.8) respectively. Falls in FEV 1 after montelukast were less than after placebo (10.6 (10.6) and 14.3 (11.3) after exercise and EVH respectively; p&lt;0.05). Montelukast provided protection against bronchoconstriction (59% and 53%; p&lt;0.05) for eight exercising subjects and 10 EVH subjects; no protection was afforded for three exercising and one EVH challenged subject. Conclusions: Both exercise and EVH were potent stimuli of airway narrowing. A single dose of montelukast provided reasonable protection in attenuating bronchoconstriction from either exercise or EVH. The similar protection by montelukast suggests that EVH is a suitable laboratory surrogate for EIB evaluation.
Clinical Applications of Stem Cells for the Heart
Authors: Kai C. Wollert, Helmut Drexler
Journal: Circulation Research (2005)

Repair of the heart is an old dream of physicians caring for patients with cardiac disease. Experimental studies suggest that cardiac transfer of stem and progenitor cells can have a favorable impact on tissue perfusion and contractile performance of the injured heart. Some researchers favor stable stem cell engraftment by fusion or transdifferentiation into cardiomyocyte or vascular cell lineages as likely explanations for these beneficial effects. Others have proposed that transient cell retention may be sufficient to promote functional effects, eg, by release of paracrine mediators. Although the mechanistic underpinnings of stem cell therapy are still intensely debated, the concept of cell therapy has already been introduced into the clinical setting, where a flurry of small, mostly uncontrolled trials indicate that stem cell therapy may be feasible in patients. The overall clinical experience also suggests that stem cell therapy can be safely performed, if the right cell type is used in the right clinical setting. Preliminary efficacy data indicate that stem cells have the potential to enhance myocardial perfusion and/or contractile performance in patients with acute myocardial infarction, advanced coronary artery disease, and chronic heart failure. The field now is rapidly moving toward intermediate-size, double-blinded trials to gather more safety and efficacy data. Ultimately, large outcome trials will have to be conducted. We need to proceed cautiously with carefully designed clinical trials and keep in mind that patient safety must remain the key concern. At the same time, continued basic research to elucidate the underlying mechanism of stem cell therapy is clearly needed.
Bifunctional major histocompatibility-linked genetic regulation of cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes.
Authors: A M Schmitt-Verhulst, G M Shearer
Journal: The Journal of Experimental Medicine (1975)

Murine thymus-derived lymphocytes can be sensitized in vitro to trinitrophenyl (TNP)-modified autologous spleen cells (1, 2). Cytotoxic effector cells were generated which were specific for TNP-modified target cells expressing the same H-2K and H-2D serological regions as the modified stimulator cells (3, 7). Spleen cells from two C57BL/10 congenic strains of mice sharing common I-C, S, and D regions, but differing at K, I-A, and I-B regions, generated different levels of lytic responses to the shared modified H-2Dd products upon sensitization with auto logous TNP-modified cells. Lymphocytes from an F1 between responder and nonresponder strain generated a level of cytolysis toward the H-2Dd modified specificity which was of the same order of magnitude as that obtained with the high responder, irrespective of whether F 1 or either parental strain of modified stimulator cell was used. These results suggest that the modification of H-2Dd products resulted in formation of new antigenic determinants in both parental strains. However, the difference observed in responsiveness appeared to be due to a gene or genes mapping in the K, I-A, or I-B region which influenced the ability of the responding lymphocytes to react to these modified H-2Dd products. Responsiveness was expressed as a dominant trait in the F1.
THE ACTION OF CARDIAC GLYCOSIDES ON ION MOVEMENTS
Authors: I.M. GLYNN
Journal: Pharmacological Reviews (1964)

It is difficult to summarise when so much that has been said is tentative but it is probably fair to state that:

1) The cardiotonic effect is not primarily on the action potential mechanism or on the contractile mechanism but is on excitation-contraction coupling.

2) The sensitivity to cardiac glycosides of the sodium and potassium transport mnechanism in the muscle membrane is sufficient for sodium and potassium transport to be affected by cardiac glycoskies in therapeutic concentrations.

Nevertheless

3) it is doubtful whether therapeutic doses of cardiac glycosides cause appreciable lowering of the internal potassium concentration. A gain in sodiumn may occur.

4) A positive inotropic action is probably associated with increased uptake of calcium.

5) It is possible that the cardiotonic action of the cardiac glycosides is caused by interference with the removal or inactivation of the calcium that enters the muscle at each contraction. Such interference might be a primary effect of the cardiac glycoside or it might be secondary to a rise in the intracellular sodium concentration.
Alterations in the TOP2A and HER2 Genes: Association With Adjuvant Anthracycline Sensitivity in Human Breast Cancers
Authors: D. J. Slamon, M. F. Press
Journal: JNCI Journal of the National Cancer Institute (2009)

In this issue of the Journal, O’Malley et al. ( 1 ) present important, critical, and compelling new evidence regarding the association between alterations in the human epidermal growth factor receptor type 2 ( HER2 ) amplicon and incremental sensitivity to anthracyclinebased adjuvant therapy for breast cancers. This report is the latest in a series of publications that question the generalized assumption that there is an incremental benefit to all breast cancer patients who receive anthracycline-based adjuvant therapy as opposed to non – anthracycline-containing adjuvant therapy. This premise has dominated the design of studies and clinical practice utilization for the vast majority of adjuvant regimens worldwide over the past 30 years. The widespread use of adjuvant anthracyclines is almost entirely based on the well-known meta-analysis published by the Early Breast Cancer Trialists ’ Collaborative Group, frequently referred to as the Oxford “Overview” ( 2 ), rather than results from any single study. Indeed, the majority of individual studies have failed to show a substantial benefit from anthracycline-based adjuvant regimens over non – anthracyclinecontaining adjuvant regimens in breast cancer. The “Overview” used data derived from more than 15 000 women enrolled in 17 separate trials to show that breast cancer patients who received an anthracycline as part of their adjuvant treatment who had an absolute 3 to 4.5 percentage point improvement in relapse-free survival (RFS ) and overall survival (OS) compared with women who received nonanthracycline regimens ( 2 ). The magnitude of these benefits has generally been considered to outweigh the well-known, long-term,
Resistance Training and Type 2 Diabetes
Authors: Neil D. Eves, Ronald C. Plotnikoff
Journal: Diabetes Care (2006)

Aerobic exercise has consistently been shown to improve glucose control (1–3), enhance insulin sensitivity (2,4,5), and improve cardiovascular risk factors such as visceral adiposity (2), lipid profile (6), arterial stiffness (7), and endothelial function (8). Consistent with this evidence, the American Diabetes Association (ADA) recommends that individuals with type 2 diabetes perform at least 150 min of moderate-intensity aerobic exercise and/or at least 90 min of vigorous aerobic exercise per week (9). Although a lifestyle modification of this nature could have substantial impact on the metabolic and cardiovascular health of this population, it is often difficult for those who have been habitually sedentary to adhere to these guidelines. Indeed, a recent population-based study found that only 28% of individuals with type 2 diabetes achieve these recommendations (10). Unfortunately, it is frequently those who would benefit the most from aerobic exercise that have the greatest difficulty performing it. For individuals with severe obesity, arthritis, physical disabilities, and/or diabetes complications, even walking for 20–30 min may be challenging, uncomfortable, and/or painful to perform. With the continued increase in the prevalence of type 2 diabetes (11), it is evident that alternate forms of physical activity that produce similar metabolic improvements to aerobic exercise may be beneficial in the management of this disease.

Resistance training has recently been recognized as a useful therapeutic tool for the treatment of a number of chronic diseases (12–19) and has been demonstrated to be safe and efficacious for the elderly (20,21) and obese (22) individuals. Similar to aerobic exercise, resistance training has been reported to enhance insulin sensitivity (23–25), daily energy expenditure (26,27), and quality of life (20,28). Furthermore, resistance training has the potential for increasing muscle strength (13,29, …
Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas
Authors: Claudia Curcio, Emma Di Carlo, Raphael Clynes, Mark J. Smyth, Katia Boggio, Elena Quaglino, Michela Spadaro, Mario P. Colombo, Augusto Amici, Pier-Luigi Lollini, Piero Musiani, Guido Forni
Journal: Journal of Clinical Investigation (2003)

Since the mechanisms by which specific immunity destroys Her-2/neu carcinoma cells are highly undetermined, these were assessed in BALB/c mice vaccinated with plasmids encoding extracellular and transmembrane domains of the protein product (p185neu) of the rat Her-2/neu oncogene shot into the skin by gene gun. Vaccinated mice rejected a lethal challenge of TUBO carcinoma cells expressing p185neu. Depletion of CD4 T cells during immunization abolished the protection, while depletion of CD8 cells during the effector phase halved it, and depletion of polymorphonuclear granulocytes abolished all protection. By contrast, Ig μ-chain gene KO mice, as well as Fcγ receptor I/III, β-2 microglobulin, CD1, monocyte chemoattractant protein 1 (MCP1), IFN-γ, and perforin gene KO mice were protected. Only mice with both IFN-γ and perforin gene KOs were not protected. Although immunization also cured all BALB/c mice bearing established TUBO carcinomas, it did not cure any of the perforin KO or perforin and IFN-γ KO mice. Few mice were cured that had knockouts of the gene for Ig μ-chain, Fcγ receptor I/III, IFN-γ, or β-2 microglobulin. Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice. The eradication of established p185neu carcinomas involves distinct mechanisms, each endowed with a different curative potential.
Divergent trends for gastric cancer incidence by anatomical subsite in US adults
Authors: M. C. Camargo, W. F. Anderson, J. B. King, P. Correa, C. C. Thomas, P. S. Rosenberg, C. R. Eheman, C. S. Rabkin
Journal: Gut (2011)

<h3>Background and aim</h3> Age-specific analyses of non-cardia gastric cancer incidence reveal divergent trends among US whites: rates are declining in individuals aged 40 years and older but rising in younger persons. To investigate this heterogeneity further, incidence trends were evaluated by anatomical subsite. <h3>Methods</h3> Gastric cancer incidence data for 1976–2007 were obtained from the US National Cancer Institute9s Surveillance, Epidemiology, and End Results (SEER) Program and the US Centers for Disease Control and Prevention9s National Program of Cancer Registries (NPCR). Incidence rates and estimated annual percentage change were calculated by age group (25–39, 40–59 and 60–84 years), race/ethnicity and subsite. <h3>Results</h3> Based on data from the nine oldest SEER registries (covering ∼10% of the US population), rates for all non-cardia subsites decreased in whites and blacks, except for corpus cancer, which increased between 1976 and 2007 with estimated annual percentage changes of 1.0% (95% CI 0.1% to 1.9%) for whites and 3.5% (95% CI 1.8% to 5.2%) for blacks. In contrast, rates for all non-cardia subsites including corpus cancer declined among other races. In combined data from NPCR and SEER registries (covering 89% of the US population), corpus cancer significantly increased between 1999 and 2007 among younger and middle-aged whites; in ethnic-specific analyses, rates significantly increased among the same age groups in non-Hispanic whites and were stable among Hispanic whites. Age-specific rates for all subsites declined or were stable in this period among blacks and other races. <h3>Conclusions</h3> Long- and short-term incidence trends for gastric cancers indicate a shifting distribution by anatomical subsite. Corpus cancer may have distinctive aetiology and changing risk factor exposures, warranting further investigation.
A conservation device for oxygen therapy in COPD
Authors: TW Evans, JC Waterhouse, AJ Suggett, P Howard
Journal: European Respiratory Journal (1988)

Patients with hypoxaemia secondary to chronic obstructive pulmonary disease (COPD) are frequently prescribed oxygen therapy for short- and long-term domiciliary use. Oxygen administered via nasal cannulae incorporating a small collapsible reservoir ("Oxymizer", Chad Therapeutics Inc., CA, USA) improves transcutaneous oxygen tensions in the short-term when compared to standard nasal cannulae. The effects of this device on arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions was assessed over 60 min in twelve patients with severe hypoxaemia (6.2 +/- 0.9 kPa, mean +/- SD) and hypercapnia (7.5 +/- 1.2 kPa). Following baseline measurements, oxygen was administered using standard nasal cannulae, and further measurements were made at 15 min intervals for at least 45 min. Patients were then changed to the "Oxymizer" and measurements continued at 15 min intervals for a further 60 min. Mean PaO2 increased by 1.1 +/- 0.78 kPa (p less than 0.001), using the "Oxymizer", but PaO2 was significantly greater after 15 min on the device than after 60 min (p less than 0.05). There was no change in PaCO2 (p greater than 0.05). The "Oxymizer" increases PaO2 compared with standard cannulae, but the effect may not be sustained.
Treatment of Postmenopausal Osteoporosis with Slow-Release Sodium Fluoride: Final Report of a Randomized Controlled Trial
Authors: C Y Pak, K Sakhaee, B Adams-Huet, V Piziak, R D Peterson, J R Poindexter
Journal: Annals of Internal Medicine (1995)

Objective: To test whether slow-release sodium fluoride inhibits spinal fractures and is safe to use. Design: Placebo-controlled randomized trial. Interventions: Slow-release sodium fluoride, 25 mg twice daily, in four 14-month cycles (12 months receiving sodium fluoride followed by 2 months not receiving it) compared with placebo. Calcium citrate, 400 mg calcium twice daily, continuously in both groups. Patients: 48 of 54 patients who received sodium fluoride and 51 of 56 patients who received placebo completed at least 1 year of the study. All patients had postmenopausal osteoporosis. Results: Compared with the placebo group, the fluoride group had a lower individual vertebral fracture rate (0.064 ± 0.182 per patient-year compared with 0.205 ± 0.297 per patient-year; P = 0.002), a higher unadjusted fracture-free rate (85.4% compared with 56.9%; P = 0.001), and a greater survival estimate (relative risk, 0.3 [95% CI, 0.12 to 0.76]) for new fractures. The recurrent spinal fracture rate did not differ between the two groups. The fluoride group had a substantial increase in L2-L4 bone mass of 4% to 5% per year for 4 years, a mean increase in femoral neck bone density of 2.38% ± 3.33% per year, and no change in radial shaft bone density. The frequency with which minor side effects and appendicular fractures occurred was similar in the two groups; no patients developed microfractures or gastric ulcers. Conclusion: Slow-release sodium fluoride and calcium citrate administered for 4 years inhibits new vertebral fractures (but not recurrent fractures), augments spinal and femoral neck bone mass, and is safe to use.