tbuckley/cabot-search huggingface dataset:
Multi-tissue coexpression networks reveal unexpected subnetworks associated with disease
Authors: Radu Dobrin, Jun Zhu, Cliona Molony, Carmen Argman, Mark L Parrish, Sonia Carlson, Mark F Allan, Daniel Pomp, Eric E Schadt
Journal: Genome biology (2009)

Obesity is a particularly complex disease that at least partially involves genetic and environmental perturbations to gene-networks connecting the hypothalamus and several metabolic tissues, resulting in an energy imbalance at the systems level.To provide an inter-tissue view of obesity with respect to molecular states that are associated with physiological states, we developed a framework for constructing tissue-to-tissue coexpression networks between genes in the hypothalamus, liver or adipose tissue. These networks have a scale-free architecture and are strikingly independent of gene-gene coexpression networks that are constructed from more standard analyses of single tissues. This is the first systematic effort to study inter-tissue relationships and highlights genes in the hypothalamus that act as information relays in the control of peripheral tissues in obese mice. The subnetworks identified as specific to tissue-to-tissue interactions are enriched in genes that have obesity-relevant biological functions such as circadian rhythm, energy balance, stress response, or immune response.Tissue-to-tissue networks enable the identification of disease-specific genes that respond to changes induced by different tissues and they also provide unique details regarding candidate genes for obesity that are identified in genome-wide association studies. Identifying such genes from single tissue analyses would be difficult or impossible.
Aldosterone and dexamethasone stimulate calcineurin activity through a transcription-independent mechanism involving steroid receptor-associated heat shock proteins.
Authors: J A Tumlin, J P Lea, C E Swanson, C L Smith, S S Edge, J S Someren
Journal: Journal of Clinical Investigation (1997)

Heat shock proteins (HSP) are components of the steroid receptor complex and are released into the cell cytosol after hormone binding. We tested whether HSPs released from steroid receptors mediate an increase in calcineurin phosphatase activity by steroid hormones. Aldosterone increased calcineurin activity in microdissected rat cortical collecting ducts (CCD) and connecting tubules, but not in proximal tubules, medullary thick ascending limb, or outer medullary collecting ducts. In contrast, 5 microM dexamethasone increased calcineurin activity in both CCD and proximal tubules. Aldosterone increased CCD calcineurin activity after 30 min and this response was blocked by spironolactone, but not by actinomycin D. An antibody recognizing HSP-56 did not change basal calcineurin activity, but completely blocked the stimulation of calcineurin by aldosterone. Rapamycin, an immunosuppressive drug that stabilizes the HSP-steroid receptor complex, also blocked the aldosterone response, whereas HSP-90 or HSP-70 increased calcineurin activity in permeabilized CCD. In summary, (a) aldosterone increases calcineurin activity in CCD through a transcription-independent process; (b) maneuvers inactivating HSP-56 or slowing HSP disassociation from the receptor complex blocks stimulation of calcineurin by steroid hormones; (c) HSP-90 and HSP-70 increase CCD calcineurin activity in the absence of steroid hormone. We conclude that HSPs released from transformed steroid receptors can stimulate calcineurin activity through a transcription-independent pathway.
Interventions for Tobacco Smoking
Authors: Tanya R. Schlam, Timothy B. Baker
Journal: Annual Review of Clinical Psychology (2013)

Around 19% of US adults smoke cigarettes, and smoking remains the leading avoidable cause of death in this country. Without treatment only ~5% of smokers who try to quit achieve long-term abstinence, but evidence-based cessation treatment increases this figure to 10% to 30%. The process of smoking cessation comprises different pragmatically defined phases, and these can help guide smoking treatment development and evaluation. This review evaluates the effectiveness of smoking interventions for smokers who are unwilling to make a quit attempt (motivation phase), who are willing to make a quit attempt (cessation phase), who have recently quit (maintenance phase), and who have recently relapsed (relapse recovery phase). Multiple effective treatments exist for some phases (cessation), but not others (relapse recovery). A chronic care approach to treating smoking requires effective interventions for every phase, especially interventions that exert complementary effects both within and across phases and that can be disseminated broadly and cost-effectively.
Effect of Ranolazine Monotherapy on Glycemic Control in Subjects With Type 2 Diabetes
Authors: Robert H. Eckel, Robert R. Henry, Patrick Yue, Arvinder Dhalla, Pamela Wong, Philip Jochelson, Luiz Belardinelli, Jay S. Skyler
Journal: Diabetes Care (2015)

Ranolazine is an antianginal drug that mediates its effects by inhibition of cardiac late sodium current. Although ranolazine is not approved for the treatment of type 2 diabetes, in post hoc analyses of pivotal angina trials, ranolazine was associated with reductions in percent glycosylated hemoglobin (HbA1c) in subjects with type 2 diabetes. The study prospectively assessed the safety and efficacy of ranolazine in subjects with type 2 diabetes with inadequate glycemic control managed by lifestyle alone.The study was conducted worldwide in 465 subjects, with baseline HbA1c of 7-10% (53-86 mmol/mol) and fasting serum glucose of 130-240 mg/dL, randomized to placebo versus ranolazine.Compared with placebo, there was a greater decline in HbA1c at week 24 from baseline (primary end point) in subjects taking ranolazine (mean difference -0.56% [-6.1 mmol/mol]; P < 0.0001). Moreover, the proportion of subjects achieving an HbA1c <7.0% was greater with ranolazine (25.6% vs. 41.2%; P = 0.0004). Ranolazine was associated with reductions in fasting (mean difference -8 mg/dL; P = 0.0266) and 2-h postprandial glucose (mean difference -19 mg/dL; P = 0.0008 vs. placebo). Subjects taking ranolazine trended toward a greater decrease from baseline in fasting insulin (P = 0.0507), a greater decrease in fasting glucagon (P = 0.0003), and a lower postprandial 3-h glucagon area under the curve (P = 0.0031 vs. placebo). Ranolazine was safe and well tolerated.Compared with placebo, use of ranolazine monotherapy over 24 weeks, in subjects with type 2 diabetes and inadequate glycemic control on diet and exercise alone, significantly reduced HbA1c and other measures of glycemic control.
Discoordinate re-expression of cardiac fetal genes in Nω-nitro-?-arginine methyl ester (?-NAME) hypertension
Authors: Y Zhang
Journal: Cardiovascular Research (2002)

Hypertension produced by chronic inhibition of nitric oxide (NO) synthase by N(omega)-nitro-L-arginine methyl ester (L-NAME) was used to determine the effect of severe pressure overload with or without left ventricular (LV) hypertrophy on the transcriptional activation of the cardiac fetal genes encoding for the natriuretic peptides (NP) atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), and for beta-myosin heavy chain (MHC) in both atrial and ventricular muscle. A previously reported association of LV hypertrophy with the activation of cardiac renin and angiotensin-converting enzyme (ACE) in this hypertension model was also investigated.Male Sprague-Dawley rats received L-NAME (75 mg/kg/day) or were left untreated for 4 (n=12) or 8 (n=12) weeks.L-NAME-treated rats became severely hypertensive in both treatment groups but only five out of 12 8-week treatment animals showed a significantly increased LV weight to body weight (BW) ratio (LVW/BW). LV ANF mRNA, but not LV BNP mRNA, correlated significantly with LVW/BW only in animals showing LV hypertrophy. No changes were observed in atrial gene expression or plasma concentration of ANF or BNP. A significant correlation was found between LVW/BW and LV renin mRNA and LV ACE activity in rats with LV hypertrophy. LV beta-MHC mRNA levels were significantly increased in the LV of rats with or without LV hypertrophy at both 4 and 8 weeks of treatment.It is concluded that pressure overload per se does not promote NP or cardiac renin-angiotensin system gene expression while increased beta-MHC expression is a marker of LV pressure overload even in the absence of LV hypertrophy. It is apparent that L-NAME causes a disruption in the coordinated transcriptional activation of cardiac fetal genes expected of hypertrophic stimuli acting on the LV.
Foreign Body in Pharynx
Authors: D. W. Williams
Journal: BMJ (1950)

BEDITrJJ _353solution until the absorption curve is identical with that of a freshly prepared glucose standard (Table III).Blood- glucose figures, determined by the method outlined below but compared with standards in a photo-electric TABLE I1I.-Method of Preparing the Secondary Standards 50 mg./100ml.78 ml.H,O, 1 5 g.CuSO .5H.0, 0-5 ml.Solution 1 150 mg./100 ml.. 48 ml.H,O, 3-0 g.CuS0,.5H,O, 0-5ml.Solution 1 300 mg./100 ml.. 45 ml.H,O. 6-0g.CuSO..5H.0, 0-0 ml.Solution I
Estrogen, natriuretic peptides and the renin–angiotensin system
Authors: M Kuroski de Bold
Journal: Cardiovascular Research (1999)

There are significant gender-specific differences in the incidence of hypertension and the clinical outcome of cardiovascular disease between premenopausal women and age-matched men, suggesting that sex hormones such as estrogen (E) might be responsible for the observed cardioprotective effects. This cardioprotective action of E is thought to involve lipoproteins. However, the effect of E on the lipid profile accounts for about 50% of the reduction in cardiovascular disease, indicating that there might be other mechanisms by which E exerts its cardioprotective effects. At present, the underlying mechanism of E action is poorly understood. In this review, the interplay between E, the natriuretic peptides (NP) and the renin–angiotensin system (RAS) is examined. It is hypothesized that E might, through endocrine and/or paracrine action, modulate cardiac NP in females by affecting the RAS either directly or indirectly.
The Health and Health Care of Lesbian, Gay, and Bisexual Adolescents
Authors: Tumaini R. Coker, S. Bryn Austin, Mark A. Schuster
Journal: Annual Review of Public Health (2010)

Adolescents face a variety of challenges in their transition to adulthood; lesbian, gay, and bisexual adolescents face these typical challenges as well as additional challenges that are related to the social stigma of their sexual orientation. For some lesbian, gay, and bisexual adolescents, this stigma may induce psychosocial stress, leading to increased health risk behaviors and poorer health outcomes. In this article, we review data on the health and health care of LGB adolescents. We examine health indicators and health risks for LGB youth, including substance use, eating disorders, suicidality, risky sexual behaviors, violence exposure and victimization, and homelessness. We also examine health care provision and utilization for LGB youth. Lastly, we discuss ways in which researchers and clinicians can improve LGB adolescent health and health care.
THE INFLUENCE OF SOME ALICYCLIC HYDROCARBONS ON THE ARGINASE ACTIVITY OF GUINEA-PIG SKIN
Authors: V. K. H. BROWN, VALERIE L. BOX
Journal: British Journal of Dermatology (1971)

Summary.— When applied to guinea‐pig skin, alicyclic hydrocarbons cause morphological changes and alter the epidermal arginase activity. The magnitude of the effect is relative to the molecular weight of the hydrocarbon applied, and the relationship of the morphological changes to the change in arginase activity is the reverse of that reported for linear hydrocarbons.
Strict bed rest after EBV implant reduces pneumothorax rate
Authors: Dominik Herzog, Stefan Hippenstiel, Dirk Schürmann, Felix Döllinger, Alexander Pöllinger, Bettina Temmesfeld-Wollbrück, Norbert Suttorp, Ralf-Harto Hübner
Journal: European Respiratory Journal (2014)

Endoscopic lung volume reduction (ELVR) with valves has been shown to improve lung function, quality of life and exercise capacity in severe COPD emphysema. A major complication directly related to valve insertion is spontaneous pneumothoraces (SP) which could be associated with early post implant physical activity.  We compared the SP rate in 72 emphysema COPD patients (68+/-7y, 63% male, FEV1 25+/-6%, RV 225+/-43%) during hospital stay following assessment for complete fissures by Chartis (Pulmonx, Inc.) and treatment with endobronchial valves. 32 consecutive patients were treated without BR restriction and without CS (No-BR/No-CS) and 40 consecutive patients with strict BR and CS (BR/CS) for two days after ELVR. The Chi-squared test was used for group comparisons.  The baseline characteristics and target lobes of both groups were similar, except for the sex ratio (No-BR/No-CS: 25 [78%] males; BR/CS: 20 [50%] males; p  These observations demonstrate that strict bed rest in the postoperative management of ELVR reduces the occurrence of SP. However, further investigations with matched sex ratio are needed to confirm the data.
Sex Differences in Diabetes and Risk of Incident Coronary Artery Disease in Healthy Young and Middle-Aged Adults
Authors: Rita Rastogi Kalyani, Mariana Lazo, Pamela Ouyang, Evrim Turkbey, Karinne Chevalier, Frederick Brancati, Diane Becker, Dhananjay Vaidya
Journal: Diabetes Care (2013)

Controversy exists about the coronary artery disease (CAD) risk conveyed by diabetes in young and middle-aged women. We investigated sex differences in CAD by diabetes status among healthy individuals with different underlying risks of heart disease.We examined subjects aged <60 years without CAD at enrollment in the high-risk GeneSTAR Study (n = 1,448; follow-up ∼12 years), Multi-Ethnic Study of Atherosclerosis (MESA; n = 3,072; follow-up ∼7 years), and National Health and Nutrition Examination Survey III (NHANES III) Mortality Follow-up Study (n = 6,997; follow-up ∼15 years). Diabetes was defined by report, hypoglycemic use, and/or fasting glucose ≥126 mg/dL. The outcome was any CAD event during follow-up (fatal CAD in NHANES).In the absence of diabetes, CAD rates were lower among women in GeneSTAR, MESA, and NHANES (4.27, 1.66, and 0.40/1,000 person-years, respectively) versus men (11.22, 5.64, and 0.88/1,000 person-years); log-rank P < 0.001 (GeneSTAR/MESA) and P = 0.07 (NHANES). In the presence of diabetes, CAD event rates were similar among women (17.65, 7.34, and 2.37/1,000 person-years) versus men (12.86, 9.71, and 1.83/1,000 person-years); all log-rank P values > 0.05. Adjusting for demographics, diabetes was associated with a significant four- to fivefold higher CAD rate among women in each cohort, without differences in men. In meta-analyses of three cohorts, additionally adjusted for BMI, smoking, hypertension, HDL, and non-HDL cholesterol, antihypertensive and cholesterol-lowering medication use, the hazard ratio of CAD in men versus women among nondiabetes was 2.43 (1.76-3.35) and diabetes was 0.89 (0.43-1.83); P = 0.013 interaction by diabetes status.Though young and middle-aged women are less likely to develop CAD in the absence of diabetes, the presence of diabetes equalizes the risk by sex. Our findings support aggressive CAD prevention strategies in women with diabetes and at similar levels to those that exist in men.
Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region
Authors: M J Bruno, E B Haverkort, G P Tijssen, G N J Tytgat, D J van Leeuwen
Journal: Gut (1998)

Background —Impeded flow of pancreatic juice due to mechanical obstruction of the pancreatic duct in patients with cancer of the pancreatic head region causes exocrine pancreatic insufficiency with steatorrhoea and creatorrhoea. This may contribute to the profound weight loss that often occurs in these patients. Aims —To investigate whether pancreatic enzyme replacement therapy prevents this weight loss. Patients —Twenty one patients with unresectable cancer of the pancreatic head region with suspected pancreatic duct obstruction, a biliary endoprosthesis in situ, and a Karnofsky performance status greater than 60. Methods —Randomised double blind trial of eight weeks with either placebo or high dose enteric coated pancreatin enzyme supplementation. All patients received dietary counselling. Results —The mean difference in the percentage change of body weight was 4.9% (p=0.02, 95% confidence interval for the difference: 0.9 to 8.9). Patients on pancreatic enzymes gained 1.2% (0.7 kg) body weight whereas patients on placebo lost 3.7% (2.2 kg). The fat absorption coefficient in patients on pancreatic enzymes improved by 12% whereas in placebo patients it dropped by 8% (p=0.13, 95% confidence interval for the difference: –6 to 45). The daily total energy intake was 8.42 MJ in patients on pancreatic enzymes and 6.66 MJ in placebo patients (p=0.04, 95% confidence interval for the difference: 0.08 to 3.44). Conclusions —Weight loss in patients with unresectable cancer of the pancreatic head region and occlusion of the pancreatic duct can be prevented, at least for the period immediately after insertion of a biliary endoprosthesis, by high dose enteric coated pancreatin enzyme supplementation in combination with dietary counselling.
Obstructive Sleep Apnea and Incident Diabetes. A Historical Cohort Study
Authors: Tetyana Kendzerska, Andrea S. Gershon, Gillian Hawker, George Tomlinson, Richard S. Leung
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Despite emerging evidence that obstructive sleep apnea (OSA) may cause metabolic disturbances independently of other known risk factors, it remains unclear whether OSA is associated with incident diabetes.To evaluate whether risk of incident diabetes was related to the severity and physiologic consequences of OSA.A historical cohort study was conducted using clinical and provincial health administrative data. All adults without previous diabetes referred with suspected OSA who underwent a diagnostic sleep study at St. Michael's Hospital (Toronto, Canada) between 1994 and 2010 were followed through health administrative data until May 2011 to examine the occurrence of diabetes. All OSA-related variables collected from the sleep study were examined as predictors in Cox regression models, controlling for sex, age, body mass index, smoking status, comorbidities, and income.Over a median follow-up of 67 months, 1,017 (11.7%) of 8,678 patients developed diabetes, giving a cumulative incidence at 5 years of 9.1% (95% confidence interval, 8.4-9.8%). In fully adjusted models, patients with apnea-hypopnea index (AHI) greater than 30 had a 30% higher hazard of developing diabetes than those with AHI less than 5. Among other OSA-related variables, AHI in rapid eye movement sleep and time spent with oxygen saturation less than 90% were associated with incident diabetes, as were heart rate, neck circumference, and sleep time.Among people with OSA, and controlling for multiple confounders, initial OSA severity and its physiologic consequences predicted subsequent risk for incident diabetes.
A STUDY OF CERTAIN ASPECTS OF BLOOD COAGULATION IN THE POSTOPERATIVE STATE IN CONGESTIVE HEART FAILURE AND IN THROMBOPHLEBITIS
Authors: Noble O. Fowler, Shirley Roehm, Harold Perlman
Journal: Journal of Clinical Investigation (1949)

In recent years a number of tests have been de- signed for the purpose of detection of accelerated blood coagulation.Among these are the lusteroid tube coagulation test (1-4), the silicone tube co- agulation test (5), the modified clot retraction test (6), the modified Lee-White clotting test, employ- ing three test tubes instead of one (7), the heparin retarded coagulation test of Waugh and Ruddick (8, 9), the heparin tolerance test ( 10, 11 ), and the prothrombin time determination, using both whole and dilute plasma (12-14).The study reported herewith was undertaken for the following purposes.First, it was desired to ascertain whether or not there is any correlation among the various tests themselves.Second, it was decided to determine whether any of these tests can be used to predict thrombophlebitis in patients.Finally, the incidence and duration of hypercoagu- lability in the postoperative state was studied, as well as the incidence of hypercoagulability in con- gestive heart failure.Incident to doing these stud- ies, observations were made on the effect of variation of tube size and temperature upon the clot- ting time of blood in the Lee-White test.Further, in doing the heparin tolerance test, blood was withdrawn almost simultaneously from the vein into which the heparin was injected and from a vein of the opposite arm.Clotting times were run on each sample and the results were compared. MATERIALFor the study on postoperative patients, a group of 29 patients in the Cincinnati General Hospital who had had recent major surgical operations was selected at random.These 29 patients and three additional patients having acute thrombophlebitis were used to determine the corre- lation among the various tests.The problem of hyper- coagulability in congestive heart failure was studied in 27 1 National Institute of Health Postdoctorate Research Fellow.patients suffering from cardiac insufficiency on the medical wards of the Cincinnati General Hospital.A group of house officers, nurses, technicians, and ambulatory psychiatric patients were used as normal controls.Per- sons from both the control group and from the post- operative group were used to study the effect of variation in temperature and tube size upon the Lee-White clotting test.Persons from both groups were also used to study the effect of the veins chosen in performing the heparin tolerance test.
Does lymphoma 'cure' rheumatoid arthritis?
Authors: A DUMAS, J STRAUCHEN
Journal: Annals of the Rheumatic Diseases (1997)

Prolonged remission in established rheumatoid arthritis (RA) is extremely rare. During a six year follow up of 458 patients Wolfe and Hawley1 observed two prolonged remissions of more than 48 months, and concluded that ‘once established, RA tends to remain, interrupted briefly in a small minority of patients by remission of disease.’ However prolonged remissions or cures have been described as secondary to Cushing’s disease2 and human immunodeficiency virus infection.3 4 We have observed a case of cure of RA accompanied by, and probably secondary to the development of γ heavy chain disease in …
Pulmonary Vascular Response to Exercise in the Dog
Authors: Ronald C. Elkins, William R. Milnor
Journal: Circulation Research (1971)

The effects of exercise on the pulmonary circulation were studied in seven experiments on five dogs. Pulsatile pulmonary arterial flow and pressure and left arterial pressure were measured by chronically implanted transducers; pulmonary vascular input impedance, resistance, and hydraulic power were computed. The average effects of running on a treadmill at 6.5 mph, as compared with the resting state, were an increase in cardiac output from 2.59 liters/ min to 5.30 liters/ min, a rise in mean pulmonary arterial pressure from 18 mm Hg to 28 mm Hg, and no consistent change in mean left arterial pressure. Pulmonary vascular resistance fell from 482 dyne sec cm at rest to 372 dyne sec cm -5 during exercise. Characteristic input impedance rose from 147 dyne sec cm-- at rest to 199 dyne sec cm -5 during exercise, and the oscillations of the impedance modulus with frequency decreased in magnitude. These changes were consistent with passive distention of the pulmonary vessels, decreasing the compliance of the large arteries and improving the impedance match between proximal and distal vessels.