tbuckley/cabot-search huggingface dataset:
α/β–T Cell Receptor (TCR)+CD4−CD8− (NKT) Thymocytes Prevent Insulin-dependent Diabetes Mellitus in Nonobese Diabetic (NOD)/Lt Mice by the Influence of Interleukin (IL)-4 and/or IL-10
Authors: Kirsten J.L. Hammond, Lynn D. Poulton, Linda J. Palmisano, Pablo A. Silveira, Dale I. Godfrey, Alan G. Baxter
Journal: The Journal of Experimental Medicine (1998)

We have previously shown that nonobese diabetic (NOD) mice are selectively deficient in α/β-T cell receptor (TCR)+CD4−CD8− NKT cells, a defect that may contribute to their susceptibility to the spontaneous development of insulin-dependent diabetes mellitus (IDDM). The role of NKT cells in protection from IDDM in NOD mice was studied by the infusion of thymocyte subsets into young female NOD mice. A single intravenous injection of 106 CD4−/lowCD8− or CD4−CD8− thymocytes from female (BALB/c × NOD)F1 donors protected intact NOD mice from the spontaneous onset of clinical IDDM. Insulitis was still present in some recipient mice, although the cell infiltrates were principally periductal and periislet, rather than the intraislet pattern characteristic of insulitis in unmanipulated NOD mice. Protection was not associated with the induction of “allogenic tolerance” or systemic autoimmunity. Accelerated IDDM occurs after injection of splenocytes from NOD donors into irradiated adult NOD recipients. When α/β-TCR+ and α/β-TCR− subsets of CD4−CD8− thymocytes were transferred with diabetogenic splenocytes and compared for their ability to prevent the development of IDDM in irradiated adult recipients, only the α/β-TCR+ population was protective, confirming that NKT cells were responsible for this activity. The protective effect in the induced model of IDDM was neutralized by anti–IL-4 and anti–IL-10 monoclonal antibodies in vivo, indicating a role for at least one of these cytokines in NKT cell-mediated protection. These results have significant implications for the pathogenesis and potential prevention of IDDM in humans.
Analogies are powerful and dangerous things
Authors: Monique Borgerhoff Mulder, Richard McElreath, Kari Britt Schroeder
Journal: Behavioral and Brain Sciences (2006)

The analogy between biological and cultural evolution is not perfect. Yet, as Mesoudi et al. show, many of the vaunted differences between cultural and genetic evolution (for example, an absence of discrete particles of cultural inheritance, and the blurred distinction between cultural replicators and cultural phenotypes) are, on closer inspection, either illusory or peripheral to the validity of the analogy. But what about horizontal transmission? We strongly agree with the authors that the potential for horizontal transmission of cultural traits does not invalidate an evolutionary approach to culture. We suggest, however, that it does require a different evolutionary treatment.
Differential Effects of an Angiotensin II Analogue on Pressor and Adrenal Receptors in the Rabbit
Authors: JOHN M. STEELE, JEROME LOWENSTEIN
Journal: Circulation Research (1974)

The 1-sarcosine-8-alanine analogue of angiotensin II (1-Sar-8-Ala-angiotensin II) was infused at 1 and 5 µg/kg min -1 into conscious rabbits on normal or sodium-deficient diets. Blood pressures during the control period were comparable in both groups; plasma renin activity, angiotensin II concentration, and aldosterone concentration were higher in the rabbits on the sodium-deficient diet than they were in the rabbits on the normal diet. The analogue caused a 6-mm Hg fall in mean arterial blood pressure in sodium-depleted rabbits. Plasma renin activity increased in both groups to eight to ten times the control values with the higher rate of infusion. Angiotensin II concentration paralleled plasma renin activity. Plasma aldosterone concentration increased after infusion of the analogue at 1 µg/kg min -1 to three to four times the control values but decreased from these high levels after an additional 90-minute infusion at 5 µg/kg min -1 to only one to two times the control values in both groups. Infusion of angiotensin II during the administration of the analogue caused a clear-cut increase in aldosterone concentration without a change in blood pressure. The persistence of elevated aldosterone levels during inhibitor blockade in the sodium-depleted rabbits does not prove that factors other than angiotensin participate in the aldosterone response to sodium deprivation. However, the data do indicate that 1-Sar-8-Ala-angiotensin II is a less effective antagonist of angiotensin II at the adrenal receptors than it is at the vascular smooth muscle receptors and suggest that the pressor and adrenal receptors differ.
BRCA2 Phosphorylated by PLK1 Moves to the Midbody to Regulate Cytokinesis Mediated by Nonmuscle Myosin IIC
Authors: Miho Takaoka, Hiroko Saito, Katsuya Takenaka, Yoshio Miki, Akira Nakanishi
Journal: Cancer Research (2014)

Cytokinesis is the critical final step in cell division. BRCA2 disruption during cytokinesis is associated with chromosome instability, but mechanistic information is lacking that could be used to prevent cancer cell division. In this study, we report that BRCA2 phosphorylation by the mitotic polo-like kinase (PLK1) governs the localization of BRCA2 to the Flemming body at the central midbody, permitting an interaction with nonmuscle myosin IIC (NM-IIC). Formation of an NM-IIC ring-like structure at the Flemming body shows that the IIC-ring relies on its ATPase activity stimulated by interaction with BRCA2 and associated proteins. Notably, inhibiting this binding inactivated the ATPase activity, causing disassembly of the IIC-ring, defective formation of the midbody, and interruption of cytokinesis. An analysis of cancer-associated mutations in BRCA2 at the PLK1-binding site suggests that they may contribute to cytokinetic defects by altering BRCA2 localization. Our findings suggest that BRCA2-dependent IIC-ring formation is a critical step in proper formation of the midbody, offering an explanation for how chromosome instability may arise in breast cancer.
The MEF2D transcription factor mediates stress-dependent cardiac remodeling in mice
Authors: Yuri Kim, Dillon Phan, Eva van Rooij, Da-Zhi Wang, John McAnally, Xiaoxia Qi, James A. Richardson, Joseph A. Hill, Rhonda Bassel-Duby, Eric N. Olson
Journal: Journal of Clinical Investigation (2008)

The adult heart responds to excessive neurohumoral signaling and workload by a pathological growth response characterized by hypertrophy of cardiomyocytes and activation of a fetal program of cardiac gene expression. These responses culminate in diminished pump function, ventricular dilatation, wall thinning, and fibrosis, and can result in sudden death. Myocyte enhancer factor–2 (MEF2) transcription factors serve as targets of the signaling pathways that drive pathological cardiac remodeling, but the requirement for MEF2 factors in the progression of heart disease in vivo has not been determined. MEF2A and MEF2D are the primary MEF2 factors expressed in the adult heart. To specifically determine the role of MEF2D in pathological cardiac remodeling, we generated mice with a conditional MEF2D allele. MEF2D-null mice were viable, but were resistant to cardiac hypertrophy, fetal gene activation, and fibrosis in response to pressure overload and β-chronic adrenergic stimulation. Furthermore, we show in a transgenic mouse model that forced overexpression of MEF2D was sufficient to drive the fetal gene program and pathological remodeling of the heart. These results reveal a unique and important function for MEF2D in stress-dependent cardiac growth and reprogramming of gene expression in the adult heart.
Antimicrobial Stewardship in Pediatrics
Authors: David Y. Hyun, Adam L. Hersh, Katie Namtu, Debra L. Palazzi, Holly D. Maples, Jason G. Newland, Lisa Saiman
Journal: JAMA Pediatrics (2013)

Antimicrobial stewardship (AS) programs are effective in improving clinical outcomes associated with antimicrobial therapies while improving patient safety by reducing adverse events and development of bacterial resistance. Understanding the basic principles of AS is essential to the successful development and implementation of AS strategies. Identifying and developing strategies to address barriers and challenges to AS can facilitate the establishment of financial, administrative, and organizational support, and agreement and participation by individual prescribers. Review of published outcomes of AS demonstrates the effectiveness in reducing unnecessary antimicrobial use and adverse events such as Clostridium difficile infections. We also illustrate the need for further research and expansion of AS activities to office-based practices and communities by using novel and innovative AS strategies and by influencing regional and national policies.
Does a Recent Cancer Diagnosis Predict Smoking Cessation? An Analysis From a Large Prospective US Cohort
Authors: J. Lee Westmaas, Christina C. Newton, Victoria L. Stevens, W. Dana Flanders, Susan M. Gapstur, Eric J. Jacobs
Journal: Journal of Clinical Oncology (2015)

Quitting smoking provides important health benefits to patients with cancer. A cancer diagnosis may motivate quitting-potentially providing a teachable moment in which oncologists can encourage and assist patients to quit-but little is known about whether a recent cancer diagnosis (including diagnosis of a cancer that is less strongly linked to smoking) is associated with increased quitting.Cancer Prevention Study-II Nutrition Cohort participants reported smoking status at enrollment in 1992 to 1993 and approximately biennially through 2009. Quit rates of smokers diagnosed with cancer during 2- and 4-year intervals were compared with those of smokers not diagnosed with cancer (12,182 and 12,538 smokers in 2- and 4-year analyses, respectively). Cancers likely to cause physical limitations or symptoms that could influence smoking (cancers of the lung, head and neck, esophagus, or any metastatic cancer) were excluded. Logistic regressions calculated quit rates controlling for age, sex, survey year, cardiovascular disease, and chronic obstructive pulmonary disease.The 2-year quit rate was higher among the 772 smokers who were diagnosed with cancer (31.3%; 95% CI, 28.0% to 34.5%) than among smokers not diagnosed with cancer (19.5%; 95% CI, 19.0% to 19.9%). A similar difference was observed for 4-year quit rates (43.0% v 33.8%). Results were similar by cancer site and stage.A diagnosis of cancer, even a cancer not strongly related to smoking and with a relatively good prognosis, may be associated with increased quitting that is sustained well after diagnosis. Results support the hypothesis that a cancer diagnosis presents a teachable moment that can be capitalized on to promote cessation.
Effects of one year's treatment with ranitidine and of truncal vagotomy on gastric contents.
Authors: J M Thomas, J J Misiewicz, A R Cook, M J Hill, P L Smith, C L Walters, J K Forster, L E Martin, D F Woodings
Journal: Gut (1987)

Fifteen patients with peptic ulcer underwent 24 hour studies of gastric contents: before and on completing six weeks' treatment with oral ranitidine 150 mg bd, twice on maintenance treatment for nine to 12 months and one month after stopping the drug. For comparison, 11 patients underwent identical 24 hour studies three to 38 months after truncal vagotomy for duodenal ulcer. During treatment with ranitidine median 24 hour intragastric pH, nitrate concentration, and counts of total and nitrate reducing bacteria increased significantly regardless of dietary nitrate content; there was no significant increase in the median day time concentration of N-nitroso compounds. Despite these changes, an acid tide at some point in each 24 hour study period prevented persistent bacterial colonisation of the stomach. There were no significant differences between the biochemical and microbiological changes recorded during one year of treatment with ranitidine, and the observations on patients after truncal vagotomy. One month after stopping one year's treatment with ranitidine all variables examined returned to pretreatment levels. Treatment with ranitidine or vagotomy was associated with significant positive correlations among pH, nitrate concentration and bacterial counts. Correlations between pH and N-nitroso compound concentration and between concentrations of nitrite and N-nitroso compounds were not significant.
Expansion of CCR8+ Inflammatory Myeloid Cells in Cancer Patients with Urothelial and Renal Carcinomas
Authors: Evgeniy Eruslanov, Taryn Stoffs, Wan-Ju Kim, Irina Daurkin, Scott M. Gilbert, Li-Ming Su, Johannes Vieweg, Yehia Daaka, Sergei Kusmartsev
Journal: Clinical Cancer Research (2013)

Chemokines are involved in cancer-related inflammation and malignant progression. In this study, we evaluated expression of CCR8 and its natural cognate ligand CCL1 in patients with urothelial carcinomas of bladder and renal cell carcinomas.We examined CCR8 expression in peripheral blood and tumor tissues from patients with bladder and renal carcinomas. CCR8-positive myeloid cells were isolated from cancer tissues with magnetic beads and tested in vitro for cytokine production and ability to modulate T-cell function.We show that monocytic and granulocytic myeloid cell subsets in peripheral blood of patients with cancer with urothelial and renal carcinomas display increased expression of chemokine receptor CCR8. Upregulated expression of CCR8 is also detected within human cancer tissues and primarily limited to tumor-associated macrophages. When isolated, CD11b(+)CCR8(+) cell subset produces the highest levels of proinflammatory and proangiogenic factors among intratumoral CD11b myeloid cells. Tumor-infiltrating CD11b(+)CCR8(+) cells selectively display activated Stat3 and are capable of inducing FoxP3 expression in autologous T lymphocytes. Primary human tumors produce substantial amounts of the natural CCR8 ligand CCL1.This study provides the first evidence that CCR8(+) myeloid cell subset is expanded in patients with cancer. Elevated secretion of CCL1 by tumors and increased presence of CCR8(+) myeloid cells in peripheral blood and cancer tissues indicate that CCL1/CCR8 axis is a component of cancer-related inflammation and may contribute to immune evasion. Obtained results also implicate that blockade of CCR8 signals may provide an attractive strategy for therapeutic intervention in human urothelial and renal cancers.
Does Inhaled Albuterol Improve Diaphragmatic Contractility in Patients with Chronic Obstructive Pulmonary Disease?
Authors: UMUR Ş. HATIPOĞLU, FRANCO LAGHI, MARTIN J. TOBIN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We tested the hypothesis that the decrease in dyspnea in patients with COPD with inhaled albuterol is in part due to increased diaphragmatic contractility. Eleven patients with COPD inhaled albuterol or placebo in a double-blind randomized manner. Subsequently, dyspnea was measured while patients breathed through inspiratory resistors, and diaphragmatic contractility was quantified during maximal inspiratory efforts and after twitch stimulation of the phrenic nerves. Albuterol produced a decrease in dyspnea (5 ± 2 to 4 ± 2 [SD] Borg units, p < 0.01), and increases in maximal transdiaphragmatic pressure (92.4 ± 37.2 to 102.8 ± 37.2 cm H2O, p < 0.03) and potentiated twitch transdiaphragmatic pressures (21.6 ± 7.1 to 25.2 ± 7.6 cm H2O, p < 0.02). The decrease in dyspnea correlated with the increases in maximal and twitch transdiaphragmatic pressures: r = − 0.64 (p = 0.04) and r = − 0.65 (p = 0.04), respectively. Compared with placebo, albuterol produced an increase in inspiratory capacity (1.87 ± 0.71 to 2.26 ± 0.74 L, p = 0.002), which accounted for the increases in maximal and twitch transdiaphragmatic pressures. The decrease in dyspnea correlated with the increase in inspiratory capacity (r = − 0.62, p = 0.04), but not with the increase in FEV1 (r = − 0.13, p = 0.72). In conclusion, albuterol relieves dyspnea and enhances respiratory muscle output in patients with COPD primarily by improving the length-tension relationship of the diaphragm rather than by improving its contractility.
Pediatric Phase I Trial and Pharmacokinetic Study of Vorinostat: A Children's Oncology Group Phase I Consortium Report
Authors: Maryam Fouladi, Julie R. Park, Clinton F. Stewart, Richard J. Gilbertson, Paula Schaiquevich, Junfeng Sun, Joel M. Reid, Matthew M. Ames, Roseanne Speights, Ashish M. Ingle, James Zwiebel, Susan M. Blaney, Peter C. Adamson
Journal: Journal of Clinical Oncology (2010)

The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of vorinostat administered as a single agent and in combination 13-cis retinoic acid (13cRA) in children with refractory solid tumors; to evaluate the tolerability of the solid tumor MTD in children with refractory leukemias; and to characterize the pharmacokinetics of a vorinostat suspension in children.Vorinostat was administered orally daily starting at 180 mg/m(2)/d with escalations planned in 30% increments. Pharmacokinetic studies were performed with the initial dose. Acetyl-histone (H3) accumulation was assessed by Western blotting of peripheral blood mononuclear cells (PBMC).Sixty-four patients were enrolled on this multipart trial. In patients with solid tumors, the MTD was 230 mg/m(2)/d with dose-limiting neutropenia, thrombocytopenia, and hypokalemia at 300 mg/m(2)/d. DLTs observed with the combination of 13cRA and vorinostat included thrombocytopenia, neutropenia, anorexia, and hypertriglyceridemia, resulting in a MTD of vorinostat 180 mg/m(2)/d 4 times per week and 13cRA 80 mg/m(2)/dose twice per day, days 1 through 14 every 28 days. Wide interpatient variability was noted in vorinostat disposition, with area under the concentration-time curves at 230 mg/m(2)/d for the capsule (range, 1,415 to 9,291 ng/mL x hr) and oral suspension (range, 1,186 to 4,780 ng/mL x hr). Significant accumulation of acetylated H3 histone in PBMC was observed after administration of vorinostat, particularly at higher doses. One patient with neuroblastoma experienced a complete response to the combination.In children with recurrent solid tumors, vorinostat is well-tolerated at 230 mg/m(2)/d, with a modest dose reduction being required when combining vorinostat with 13cRA. Drug disposition is similar to that observed in adults.
29 NEITHER MULTIPLE TUMORS NOR PORTAL HYPERTENSION ARE OPERATIVE CONTRAINDICATIONS FOR HEPATOCELLULAR CARCINOMA
Authors: T. Ishizawa, K. Hasegawa, T. Aoki, M. Takahashi, Y. Inoue, H. Imamura, Y. Sugawara, N. Kokudo, M. Makuuchi
Journal: Journal of Hepatology (2008)
Descriptive epidemiology of intravenous heroin users—A new risk group for transmission of HIV in India
Authors: S. Sarkar, P. Mookerjee, A. Roy, T.N. Naik, J.K. Singh, A.R. Sharma, Y. Ibotombi Singh, P.K. Singh, S.P. Tripathy, S.C. Pal
Journal: Journal of Infection (1991)
EXPERIMENTAL PULMONARY TUBERCULOSIS IN THE DOG
Authors: Paul A. Lewis, Charles M. Montgomery
Journal: The Journal of Experimental Medicine (1913)

It is obvious, as stated in the beginning, that these experiments have failed to reproduce a chronic pulmonary tuberculosis. Acute pneumonic processes of tubercular origin are, however, not infrequent as a complicating or terminal process in pulmonary phthisis, and there have been several cases described in which individuals have died with the symptom complex of acute lobar pneumonia, in which it developed at post-mortem examination that the disease was tuberculosis. Our experiments throw some light on debated questions in connection with these acute pneumonic forms of phthisis. In our experiments we believe that we have effectively reproduced this exudative type of tuberculosis of the lungs. This type of lesion may, in the light of our experiments, result from the sudden bronchogenic invasion of large numbers of virulent tubercle bacilli in a relatively resistant animal. The large mononuclear cells so frequently encountered in the exudate seem to be brought there chiefly from outside.(1) As Orth found when studying human material, it is difficult here also, to exclude the possibility that similar cells may result from the desquamation of alveolar epithelium. The tubercle bacillus alone, without the aid of secondary infection, is competent to produce a type of lesion which leads to necrosis of the bronchi, and by discharge of the necrotic material to cavity formation. As judged by our experiments the bronchi are less resistant to involvement in the necrosis than are the blood vessels or pleural surfaces. The fact that by the method of bronchial insufflation of Lamar and Meltzer a characteristic tuberculous pneumonia may be produced makes it probable that the lobar pneumonias generally are of bronchogenic origin.
Interferon Gamma-1b for the Treatment of Idiopathic Pulmonary Fibrosis
Authors: R.M. du Bois
Journal: New England Journal of Medicine (1999)

Idiopathic pulmonary fibrosis is a chronic condition of the lung parenchyma involving progressive injury, inflammation, and fibrosis. Data collected from October 1988 through September 1990 in the population-based registry of patients with diffuse lung disease in Bernalillo County, New Mexico, suggest that the prevalence of this disease is roughly 20 cases per 100,000 men and 13 per 100,000 women.1 Idiopathic pulmonary fibrosis has the highest mortality of all of the diffuse lung diseases. Mortality rates from the disease almost doubled in England and Wales between 1979 and 1988,2 an increase that was not due to differences in the way the . . .
Validation of the Auto-Inflammatory Diseases Activity Index (AIDAI) for hereditary recurrent fever syndromes
Authors: Maryam Piram, Isabelle Koné-Paut, Helen J Lachmann, Joost Frenkel, Seza Ozen, Jasmin Kuemmerle-Deschner, Silvia Stojanov, Anna Simon, Martina Finetti, Maria Pia Sormani, Alberto Martini, Marco Gattorno, Nicolino Ruperto
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To validate the Auto-Inflammatory Diseases Activity Index (AIDAI) in the four major hereditary recurrent fever syndromes (HRFs): familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and cryopyrin-associated periodic syndromes (CAPS). <h3>Methods</h3> In 2010, an international collaboration established the content of a disease activity tool for HRFs. Patients completed a 1-month prospective diary with 12 yes/no items before a clinical appointment during which their physician assessed their disease activity by a questionnaire. Eight international experts in auto-inflammatory diseases evaluated the patient9s disease activity by a blinded web evaluation and a nominal group technique consensus conference, with their consensus judgement considered the gold standard. Sensitivity/specificity/accuracy measures and the ability of the score to discriminate active from inactive patients via the best cut-off score were calculated by a receiver operating characteristic analysis. <h3>Results</h3> Consensus was achieved for 98/106 (92%) cases (39 FMF, 35 CAPS, 14 TRAPS and 10 MKD), with 26 patients declared as having inactive disease and 72 as having active disease. The median total AIDAI score was 14 (range=0–175). An AIDAI cut-off score ≥9 discriminated active from inactive patients, with sensitivity/specificity/accuracy of 89%/92%/90%, respectively, and an area under the curve of 98% (95% CI 96% to 100%). <h3>Conclusions</h3> The AIDAI score is a valid and simple tool for assessing disease activity in FMF/MKD/TRAPS/CAPS. This tool is easy to use in clinical practice and has the potential to be used as the standard efficacy measure in future clinical trials.