tbuckley/cabot-search huggingface dataset:
Tbx2 Directly Represses the Expression of the p21WAF1 Cyclin-Dependent Kinase Inhibitor
Authors: Sharon Prince, Suzanne Carreira, Keith W. Vance, Amaal Abrahams, Colin R. Goding
Journal: Cancer Research (2004)

T-box factors play a crucial role in the development of many tissues, and mutations in T-box factor genes have been implicated in multiple human disorders. Some T-box factors have been implicated in cancer; for example, Tbx2 and Tbx3 can suppress replicative senescence, whereas Tbx3 can cooperate with Myc and Ras in cellular transformation. The p21(WAF1) cyclin-dependent kinase inhibitor plays a key role in senescence and in cell cycle arrest after DNA damage. Here, using a combination of in vitro DNA-binding, transfection, and chromatin immunoprecipitation assays, we show that Tbx2 can bind and repress the p21 promoter in vitro and in vivo. Moreover, small interfering RNA-mediated down-regulation of Tbx2 expression results in a robust activation of p21 expression. Taken together, these results implicate Tbx2 as a novel direct regulator of p21 expression and have implications for our understanding of the role of T-box factors in the regulation of senescence and oncogenesis, as well as in development.
Expression of the selenoprotein S (SELS) gene in subcutaneous adipose tissue and SELS genotype are associated with metabolic risk factors
Authors: Maja Olsson, Bob Olsson, Peter Jacobson, Dag S Thelle, Johan Björkegren, Andrew Walley, Philippe Froguel, Lena M S Carlsson, Kajsa Sjöholm
Journal: Metabolism (2010)

The selenoprotein S (SELS) is a putative receptor for serum amyloid A, and recent studies have suggested that SELS may be a link between type 2 diabetes mellitus and inflammation. Genetic studies of SELS polymorphisms have revealed associations with circulating levels of inflammatory markers and hard end points of cardiovascular disease. In this study, we analyzed SELS expression in subcutaneous adipose tissue and SELS genotype in relation to metabolic risk factors. DNA microarray expression analysis was used to study the expression of SELS in lean and obese siblings from the Swedish Obese Subjects Sib Pair Study. TaqMan genotyping was used to analyze 3 polymorphisms, previously found to be associated with circulating levels of inflammatory markers, in the INTERGENE case-control study of myocardial infarction and unstable angina pectoris. Possible associations between SELS genotype and/or expression with anthropometry and measures of metabolic status were investigated. Real-time polymerase chain reaction was used to analyze the SELS expression in isolated human adipocytes incubated with insulin. In lean subjects, we found correlations between SELS gene expression in subcutaneous adipose tissue and measures of obesity (waist, P = .045; sagittal diameter, P = .031) and blood pressure (diastolic, P = .016; systolic P = .015); and in obese subjects, we found correlations with measures of obesity (body mass index, P = .03; sagittal diameter, P = .008) and glycemic control (homeostasis model assessment of insulin resistance, P = .011; insulin, P = .009) after adjusting for age and sex. The 5227GG genotype was associated with serum levels of insulin (P = .006) and homeostasis model assessment of insulin resistance (P = .007). The expression of SELS increased after insulin stimulation in isolated human adipocytes (P = .008). In this study, we found an association between both SELS gene expression in adipose tissue and SELS genotype with measures of glycemic control. In vitro studies demonstrated that the SELS gene is regulated by insulin in human subcutaneous adipocytes. This study further supports a role for SELS in the development of metabolic disease, especially in the context of insulin resistance.
Ciclesonide improves measures of small airway involvement in asthma
Authors: J. Cohen, W. R. Douma, N. H. T. ten Hacken, J. M. Vonk, M. Oudkerk, D. S. Postma
Journal: European Respiratory Journal (2008)

Ciclesonide is delivered as a small-particle inhaled corticosteroid and improves lung function and airway hyperresponsiveness. The objective of the present study was to assess whether ciclesonide can specifically improve small airway function in asthma. A total of 16 mild-to-moderate asthma patients (seven males; median (range) age 39 (19–56) yrs and forced expiratory volume in one second (FEV 1 ) 89 (62–120)% predicted) were randomised to 5 weeks’ treatment with placebo or 320 μg ciclesonide once daily. The following small airway parameters were assessed: mean forced expiratory flow between 25 and 75% of forced vital capacity (FVC), percentage fall in FVC at provocative dose of adenosine-5′-monophosphate and of methacholine (MCh) causing a 20% fall in FEV 1 , expiratory lung volume on computed tomography (CT) scan after MCh challenge, single-breath nitrogen closing volume and alveolar exhaled nitric oxide (eNO). Seven subjects received placebo and nine received ciclesonide. Both alveolar eNO and CT measurements of expiratory lung volume after MCh challenge decreased significantly with ciclesonide (median (range) decrease 4.4 (54.8–1.4) ppb and 59 (1,569– -117) mL, respectively), and compared with placebo (-0.4 (7.3– -3.4) ppb and -121 (20– -236) mL respectively). Ciclesonide did not significantly improve other small airways parameters. Inflammation and patency of small airways, reflected by alveolar exhaled nitric oxide and air trapping on computed tomography scan, both improve with ciclesonide even in this small number of patients. This indicates that ciclesonide exerts anti-inflammatory effects on small airways.
COMFORT, EFFECTIVENESS, AND SELF-AWARENESS AS CRITERIA OF IMPROVEMENT IN PSYCHOTHERAPY
Authors: MORRIS B. PARLOFF, HERBERT C. KELMAN, JEROME D. FRANK
Journal: American Journal of Psychiatry (1954)

Since improvement under psychotherapy is not a unitary phenomenon, progress in studying the effectiveness of psychotherapy depends on the use of carefully defined and generally agreed upon criteria of improvement. In the present state of knowledge such criteria must be based on value judgments by the patient, and by persons with whom he interacts. It is suggested that the criteria comfort and effectiveness represent these values. Means of measuring them are described and problems connected with the measures considered. Some implications of the viewpoint that improvement must be evaluated in terms of underlying personality changes are discussed. A simple measure of self-awareness is described which may be a possible indicator of certain such changes.
Debating transversus abdominis, the “exercise pill” and whether flying limits athletes’ performance on arrival
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2008)

In this issue of BJSM , Allison and Morris ( see page 930 )1 question some fundamental beliefs regarding core stability. Whether or not you agree with them, the paper raises an important issue. It is difficult to move research into practice but sometimes practice behaviours do seem to take off ahead of the clinical evidence. Is this the case here or not? Make up your own mind. Associate Editor Professor Paul Hodges responds in December's BJSM .

Jill Cook ( see page 863 )2 takes this issue and considers it more broadly. Are all those patients who worked diligently on the Cybex machine in the 1980s better off for that? (I can see the younger reader yelling out: “Hey Mum, what’s a Cybex?”). But I digress. The editorial reminds both clinicians and scientists that close communication is essential. As one of the worlds leading …
Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal?
Authors: John Pernow, Christian Jung
Journal: Cardiovascular Research (2013)

Functional integrity of the vascular endothelium is of fundamental importance for normal vascular function. A key factor regulating endothelial function is the bioavailability of nitric oxide (NO). Recently, the enzyme arginase has emerged as an important regulator of NO production by competing for l-arginine, which is a substrate for both arginase and NO synthase. Increased activity of arginase may reduce the availability of l-arginine for NO synthase, thus reducing NO production, increasing formation of reactive oxygen species, and leading ultimately to endothelial dysfunction. Increased activity and expression of arginase have been demonstrated in several pathological cardiovascular conditions, including hypertension, pulmonary arterial hypertension, atherosclerosis, myocardial ischaemia, congestive heart failure, and vascular dysfunction in diabetes mellitus. Experimental studies have demonstrated that inhibition of arginase under these conditions increases NO bioavailability, reduces oxidative stress, improves vascular function, and protects against ischaemia–reperfusion injury. Initial clinical interventional studies are also promising. The purpose of this review is to discuss the role of arginase in cardiovascular pathologies, its contribution to the development of several cardiovascular disease states and the feasibility of using arginase inhibition as a therapeutic strategy.
The Zollinger-Ellison syndrome due to an infiltrating tumour of the stomach
Authors: C. M. S. Royston, D. St. J. Brew, J. R. Garnham, B. H. Stagg, J. Polak
Journal: Gut (1972)

This is the first case report of the Zollinger-Ellison syndrome due to an infiltrating tumour of the stomach. Plasma gastrin levels were high and gastrin was demonstrated in argyrophil tumour cells by an immunofluorescent technique. Evidence is presented that the tumour arose from the G cells.
Phase III Trial Comparing Carboplatin, Paclitaxel, and Bexarotene With Carboplatin and Paclitaxel in Chemotherapy-Naïve Patients With Advanced or Metastatic Non–Small-Cell Lung Cancer: SPIRIT II
Authors: George R. Blumenschein, Fadlo R. Khuri, Joachim von Pawel, Ulrich Gatzemeier, Wilson H. Miller, Robert M. Jotte, Jacques Le Treut, Show-Li Sun, Jinkun K. Zhang, Zofia E. Dziewanowska, Andres Negro-Vilar
Journal: Journal of Clinical Oncology (2008)

The purpose of this study was to determine whether addition of the synthetic rexinoid bexarotene (Targretin; Eisai Inc, Woodcliff Lake, NJ) to standard first-line carboplatin and paclitaxel therapy provides additional survival benefit in patients with advanced non-small-cell lung cancer (NSCLC).Patients with stage IIIB disease with pleural effusion, or stage IV NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1, were randomly assigned to bexarotene 400 mg/m(2)/d combined with carboplatin and paclitaxel, or assigned to carboplatin and paclitaxel alone. Bexarotene patients also received lipid-lowering agents on or before day 1. The primary efficacy end point was overall survival; secondary efficacy and supportive analyses were also conducted.A total of 612 patients (306 per arm) were enrolled onto the study. In the intent-to-treat population, no significant difference in survival occurred between the two arms. However, a subpopulation (approximately 40%) of bexarotene-treated patients who experienced National Cancer Institute grade 3/4 hypertriglyceridemia had significantly longer median survival than control patients (12.4 v 9.2 months; log-rank, P = .014). Bexarotene-treated patients with grade 3/4 hypertriglyceridemia who received the most benefit included those who were male, were smokers, experienced 6-month prior weight loss >or= 5%, and had stage IV disease. The incidence and severity of most adverse events were similar between arms, although hyperlipidemia, neutropenia, fatigue, leukopenia, arthralgia, and diarrhea were more frequent in the bexarotene arm.Although the addition of bexarotene to chemotherapy did not improve survival in the overall study population, occurrence of high-grade hypertriglyceridemia in bexarotene-treated patients strongly correlated with increased survival, suggesting that bexarotene may benefit a segment of first-line NSCLC patients.
The Double Disparity Facing Rural Local Health Departments
Authors: Jenine K. Harris, Kate Beatty, J.P. Leider, Alana Knudson, Britta L. Anderson, Michael Meit
Journal: Annual Review of Public Health (2015)

Residents of rural jurisdictions face significant health challenges, including some of the highest rates of risky health behaviors and worst health outcomes of any group in the country. Rural communities are served by smaller local health departments (LHDs) that are more understaffed and underfunded than their suburban and urban peers. As a result of history and current need, rural LHDs are more likely than their urban peers to be providers of direct health services, leading to relatively lower levels of population-focused activities. This review examines the double disparity faced by rural LHDs and their constituents: pervasively poorer health behaviors and outcomes and a historical lack of investment by local, state, and federal public health entities.
Monitoring mast cell activation by prostaglandin D2 in vivo
Authors: S-E Dahlen
Journal: Thorax (2004)

<h3>BACKGROUND:</h3> Unplanned extubation (UE) is an important quality metric in the neonatal ICU that is associated with hypoxia, bradycardia, and risk for airway trauma with emergent re-intubation. Initial efforts to reduce UE in our level 4 neonatal ICU included standardized securement of the endotracheal tube (ETT) and requiring multiple providers to be present for ETT adjustments and patient positioning as phase 1 interventions. After an initial decline, the UE rate plateaued; an internal retrospective review revealed that the odds of UE were 2.9 times higher in the setting of an ETT tip at or above T1 (high ETT) on chest radiograph just prior to UE. The team hypothesized that advancing ETT tips to below T1 would reduce UE risk in infants of all gestational ages. <h3>METHODS:</h3> Over a period of 32 months, we compared pre-intervention and post-intervention UE rates in our neonatal ICU after a 2-step initiative that focused initially on ETT securement and assessment, with a subsequent addition of a single intervention to advance ETT tips below T1. To determine if the decrease in UE rate could be secondary to our intervention, data were analyzed from 3 cohorts: a control group of 40 infants with 185 chest radiographs and no UEs, 46 infants with chest radiographs prior to 58 UE events before the intervention, and 37 infants with chest radiographs prior to 48 UE events following the intervention. <h3>RESULTS:</h3> Advancing ETT tips below T1, in addition to the use of a standard UE-prevention bundle, led to a significant decrease in the UE rate from 1.23 to 0.91 UEs per 100 ventilator days, with 14% of postintervention UEs attributed to ETT advancement. <h3>CONCLUSIONS:</h3> High ETTs are significantly associated with UEs in the neonatal ICU. Optimizing ETT position may be an underrecognized driver in the provider's toolbox to reduce UEs. Because ETT repositioning carries risk of UE, extra caution should be taken during advancement.
Growth Hormone and Prolactin in Unipolar and Bipolar Depressed Patients: Responses to Hypoglycemia and L-Dopa
Authors: EDWARD J. SACHAR, ANDREW G. FRANTZ, NORMAN ALTMAN, JON SASSIN
Journal: American Journal of Psychiatry (1973)

In response to both insulin-induced hypoglycemia and the ingestion of 500 mg. of L-dopa, unipolar depressed patients (most of whom were postmenopausal women) secreted significantly less growth hormone (GH) than did normal subjects or bipolar depressed patients in the same age range (45 to 70 years). Prolactin responses to L-dopa were normal for nearly all subjects. Since it is believed that prolactin responses to L-dopa are mediated by brain dopamine and GH responses by brain norepinephrine, the data tend to support the hypothesis that there is a disturbance of brain norepinephrine metabolism in unipolar depressive illness. However, further study is needed to determine the effects of the menopause on GH secretion.
A Two-hybrid Screen Identifies Cathepsins B and L as Uncoating Factors for Adeno-associated Virus 2 and 8
Authors: Bassel Akache, Dirk Grimm, Xuan Shen, Sally Fuess, Stephen R Yant, Dariya S Glazer, Julie Park, Mark A Kay
Journal: Molecular Therapy (2007)

Vectors based on different serotypes of adeno-associated virus hold great promise for human gene therapy, based on their unique tissue tropisms and distinct immunological profiles. A particularly interesting candidate is AAV8, which can efficiently and rapidly transduce a wide range of tissues in vivo. To further unravel the mechanisms behind AAV8 transduction, we used yeast two-hybrid analyses to screen a mouse liver complementary DNA library for cellular proteins capable of interacting with the viral capsid proteins. In total, we recovered approximately 700 clones, comprising over 300 independent genes. Sequence analyses revealed multiple hits for over 100 genes, including two encoding the endosomal cysteine proteases cathepsins B and L. Notably, these two proteases also physically interacted with the corresponding portion of the AAV2 capsid in yeast, but not with AAV5. We demonstrate that cathepsins B and L are essential for efficient AAV2- and AAV8-mediated transduction of mammalian cells, and document the ability of purified cathepsin B and L proteins to bind and cleave intact AAV2 and AAV8 particles in vitro. These data suggest that cathepsin-mediated cleavage could prime AAV capsids for subsequent nuclear uncoating, and indicate that analysis of additional genes recovered in our screen may help to further elucidate the mechanisms behind transduction by AAV8 and related serotypes.
Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer
Authors: Y. Matsumura, M. Gotoh, K. Muro, Y. Yamada, K. Shirao, Y. Shimada, M. Okuwa, S. Matsumoto, Y. Miyata, H. Ohkura, K. Chin, S. Baba, T. Yamao, A. Kannami, Y. Takamatsu, K. Ito, K. Takahashi
Journal: Annals of Oncology (2004)
Differential Regulation of Basolateral Cl−/HCO3 − Exchangers SLC26A7 and AE1 in Kidney Outer Medullary Collecting Duct
Authors: Sharon Barone, Hassane Amlal, Jie Xu, Minna Kujala, Juha Kere, Snezana Petrovic, Manoocher Soleimani
Journal: Journal of the American Society of Nephrology (2004)

SLC26A7 is a recently identified Cl(-)/HCO(3)(-) exchanger that co-localizes with AE1 on the basolateral membrane of Alpha intercalated cells (A-IC) in outer medullary collecting duct (OMCD). The purpose of these studies was to determine whether AE1 and SLC26A7 are differentially regulated in OMCD in pathophysiologic states. Toward this end, the expression and regulation of AE1 and SLC26A7 was examined in water deprivation, a condition known to increase the osmolality of the medulla. Rats were subjected to 3 d of water deprivation while having free access to food. Northern hybridizations demonstrated that in the outer medulla, the mRNA expression of SLC26A7 increased by approximately 300% (P < 0.01 versus control; n = 3), whereas the expression of AE1 decreased by approximately 50% (P < 0.05 versus control, n = 3) in water-deprived rats. Immunoblot analysis studies demonstrated that in the outer medulla, SLC26A7 abundance increased by approximately 3.5-fold (P < 0.02 versus control; n = 3), whereas the AE1 abundance decreased by approximately 55% (P < 0.05 versus control) in water deprivation. The expression of SLC26A7 remained unchanged in the kidney cortex and stomach in water deprivation, indicating the specificity of SLC26A7 upregulation in outer medulla. In situ hybridization indicated the exclusive expression of SLC26A7 in the outer medulla and double immunofluorescence labeling confirmed the co-localization of AE1 and SLC26A7 on the basolateral membrane of A-IC cells in OMCD. It is concluded that AE1 and SLC26A7 are differentially regulated in OMCD in water deprivation. On the basis of these results and previous functional studies indicating the activation of SLC26A7 activity by high osmolality, it is proposed that SLC26A7 may play an important role in bicarbonate reabsorption and or cell volume regulation in OMCD (specifically under hypertonic conditions).
STREPTOCOCCAL PYODERMA AND ACUTE NEPHRITIS IN TRINIDAD
Authors: D. C. J. BASSETT
Journal: British Journal of Dermatology (1972)

Summary.— Following the major epidemic of acute glomerulonephritis in Trinidad in 1964 and 1965, streptococcal skin infection was studied among schoolchildren. Infection was found on 1.5% of the children in an urban school. Simultaneous infections with more than one strain of Streptococcus pyogenes were found in some children, and also the replacement of one strain by another between weekly swabbings. Skin infection was more prevalent at a rural school (15%). In a year‐long study the frequency of infection was found to be related to poverty, and to age and sex, diminishing with increasing age more rapidly in females than in males. The average for the school was one new streptococcal infection per child per 10 weeks. Spread was usually from skin to skin, possibly assisted by non‐biting Hippelates flies; involvement of nose or throat was commonly secondary to skin infection.
Aortic Arch Plaques and Risk of Recurrent Stroke and Death
Authors: Marco R. Di Tullio, Cesare Russo, Zhezhen Jin, Ralph L. Sacco, J.P. Mohr, Shunichi Homma
Journal: Circulation (2009)

Background— Aortic arch plaques are a risk factor for ischemic stroke. Although the stroke mechanism is conceivably thromboembolic, no randomized studies have evaluated the efficacy of antithrombotic therapies in preventing recurrent events. Methods and Results— The relationship between arch plaques and recurrent events was studied in 516 patients with ischemic stroke who were double-blindly randomized to treatment with warfarin or aspirin as part of the Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS), based on the Warfarin-Aspirin Recurrent Stroke Study (WARSS). Plaque thickness and morphology were evaluated by transesophageal echocardiography. End points were recurrent ischemic stroke or death over a 2-year follow-up. Large plaques (≥4 mm) were present in 19.6% of patients; large complex plaques (those with ulcerations or mobile components) were seen in 8.5%. During follow-up, large plaques were associated with a significantly increased risk of events (adjusted hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.04 to 4.32), especially those with complex morphology (HR, 2.55; 95 CI, 1.10 to 5.89). The risk was highest among cryptogenic stroke patients, both for large plaques (HR, 6.42; 95% CI, 1.62 to 25.46) and large complex plaques (HR, 9.50; 95% CI, 1.92 to 47.10). Event rates were similar in the warfarin and aspirin groups in the overall study population (16.4% versus 15.8%; P =0.43). Conclusions— In patients with stroke, especially cryptogenic stroke, large aortic plaques remain associated with an increased risk of recurrent stroke and death at 2 years despite treatment with warfarin or aspirin. Complex plaque morphology confers a slight additional increase in risk.