tbuckley/cabot-search huggingface dataset:
Effects of Insulin and Glucose on Very Low Density Lipoprotein Triglyceride Secretion by Cultured Rat Hepatocytes
Authors: Paul N. Durrington, Roger S. Newton, David B. Weinstein, Daniel Steinberg
Journal: Journal of Clinical Investigation (1982)

The effect of insulin on hepatic triglyceride synthesis and secretion is controversial. Previously, we have described a cell culture system of adult rat hepatocytes that synthesize and secrete very low density lipoprotein (VLDL) triglycerides with small and irreproducible effects of insulin on triglyceride metabolism. To study the primary effects of insulin on hepatic triglyceride metabolism a method was developed utilizing fibronectin-coated culture dishes that allowed adhesion, spreading, and maintenance of hepatocytes for 2-3 d in the absence of serum and insulin. This culture system allowed mass measurements of both cellular and secreted VLDL triglycerides for long time periods after the addition of physiological concentrations of insulin to hormone-free culture medium. In the absence of insulin and after an initial 4 h in culture, the medium was replenished and triglyceride mass was measured at the end of 18-h incubations. VLDL triglyceride accumulated in the culture medium at a linear rate over this time-course with increasing accumulation as the medium glucose concentration was raised from 2.5 to 25 mM glucose (1.77±0.24 to 3.09±0.76 μg triglyceride/mg cell protein per h). There was no apparent significant lipolysis or hepatocellular reuptake of secreted VLDL triglycerides. In the absence of insulin cellular triglyceride levels were unchanged between 3 and 24 h in culture while insulin (50-500 μU/ml) significantly increased cellular triglyceride content at all glucose concentrations tested (0-25 mM). The addition of insulin to the culture medium progressively reduced the rate of VLDL triglyceride secretion accompanied by an increase in cellular triglyceride at insulin concentrations > 50 μU/ml. Most or all of the observed increase in cell triglyceride content could in all experiments be accounted for by the insulin-induced inhibition of VLDL secretion. Incorporation of [2-3H]glycerol into cellular and VLDL triglycerides as a function of insulin concentration was also measured. Glycerol incorporation data at 20-22 h after plating of the cells closely paralleled the insulin-induced changes in cellular and VLDL triglyceride as determined by mass analysis. The observed effects of insulin occurred at concentrations close to the physiological range and suggest that the direct hepatic effect is to suppress VLDL secretion although the net effect in vivo will clearly reflect many additional accompanying changes.
Unique SDF-1–induced activation of human precursor-B ALL cells as a result of altered CXCR4 expression and signaling
Authors: Asaf Spiegel, Orit Kollet, Amnon Peled, Loya Abel, Arnon Nagler, Bella Bielorai, Gideon Rechavi, Josef Vormoor, Tsvee Lapidot
Journal: Blood (2003)
Effect of acute hypertension on sodium reabsorption by the proximal tubule
Authors: Karl M. Koch, Hagop S. Aynedjian, Norman Bank
Journal: Journal of Clinical Investigation (1968)

The effect of acute hypertension on sodium reabsorption by the proximal tubule was studied in rats by means of micropuncture methods. Hypertension was induced by bilateral carotid artery ligation and cervical vagotomy. Within a few minutes after blood pressure rose (30-60 mm Hg above control levels), a moderate natriuresis and diuresis began. Proximal sodium reabsorption, measured by two independent methods, was found to be markedly suppressed, both in absolute amount per unit length and per unit of tubular volume (C/pir(2)). The ratio between tubular volume and glomerular filtration rate (GFR) (pir(2)d/V(0)) was found to be increased. These observations indicate that the inhibition of proximal sodium reabsorption induced by hypertension cannot be explained by the tubular geometry hypothesis of sodium regulation. Several possible hormonal mechanisms were investigated. Intravenous d-aldosterone did not prevent the suppression of sodium transport due to acute hypertension, nor did chronic oral saline loading to reduce the renal content of renin. Constriction of the suprarenal aorta, with maintenance of a normal renal perfusion pressure, did prevent the inhibition of proximal transport during carotid artery occlusion, thus excluding an extrarenally produced natriuretic hormone as the mechanism. The observations are compatible with the view that sodium transport was inhibited either by an intrarenal natriuretic hormone or by an increase in the interstitial volume of the kidney produced by a transient hydrostatic pressure gradient across the peritubular capillaries. The latter seems more likely to us because of the rapidity of onset of the natriuresis, and because removing the renal capsule and releasing the surface interstitial fluid prevented the effect of hypertension on proximal sodium transport.
Higher Prevalence of Elevated Albumin Excretion in Youth With Type 2 Than Type 1 Diabetes
Authors: David M. Maahs, Beverly M. Snively, Ronny A. Bell, Lawrence Dolan, Irl Hirsch, Giuseppina Imperatore, Barbara Linder, Santica M. Marcovina, Elizabeth J. Mayer-Davis, David J. Pettitt, Beatriz L. Rodriguez, Dana Dabelea
Journal: Diabetes Care (2007)

To estimate the prevalence of an elevated albumin-to-creatinine ratio (ACR) (> or = 30 microg/mg) among youth with type 1 or type 2 diabetes and to identify factors associated with elevated ACR and their effect on the relationship between elevated ACR and type of diabetes.Cross-sectional data were analyzed from 3,259 participants with onset of diabetes at < 20 years of age in the SEARCH for Diabetes in Youth, a multicenter observational study of diabetes in youth. Multiple logistic regression was used to explore determinants of elevated ACR and factors accounting for differences in this prevalence between type 2 and type 1 diabetes.The prevalence of elevated ACR was 9.2% in type 1 and 22.2% in type 2 diabetes (prevalence ratio 2.4 [95% CI 1.9-3.0]; P < 0.0001). In multiple logistic regression analysis, female sex, A1C and triglyceride values, hypertension, and type of diabetes (type 2 versus type 1) were significantly associated with elevated ACR. Adjustment for variables related to insulin resistance (obesity, hypertension, dyslipidemia, and inflammation) attenuated, but did not completely explain, the association of diabetes type with elevated ACR.Youth with type 2 diabetes have a higher prevalence of elevated ACR than youth with type 1 diabetes, in an association that apparently does not completely depend on age, duration of diabetes, race/ethnicity, sex, level of glycemic control, or features of insulin resistance.
Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: similarity to neuroprotective strategies in hibernation and hypoxia-tolerant states
Authors: Mary P Stenzel-Poore, Susan L Stevens, Zhigang Xiong, Nikola S Lessov, Christina A Harrington, Motomi Mori, Robert Meller, Holly L Rosenzweig, Eric Tobar, Tatyana E Shaw, Xiangping Chu, Roger P Simon
Journal: The Lancet (2003)
A novel activation pathway for mature thymocytes. Costimulation of CD2 (T,p50) and CD28 (T,p44) induces autocrine interleukin 2/interleukin 2 receptor-mediated cell proliferation.
Authors: S Y Yang, S M Denning, S Mizuno, B Dupont, B F Haynes
Journal: The Journal of Experimental Medicine (1988)

Prior studies have shown that thymocytes, unlike peripheral T cells, do not proliferate in response to mitogenic combinations of anti-CD2 mAbs. The present study demonstrated that stimulation by a mitogenic anti-CD2 combination (9-1 plus 9.6) with anti-CD28 induced vigorous thymocyte proliferation in the absence of exogenous IL-2. This thymocyte proliferation was IL-2 dependent as shown by the complete inhibition using anti-IL-2-R mAbs. Induction of IL-2-R transcripts was detected in thymocytes stimulated by the anti-CD2 antibody combination alone or the anti-CD2 combination plus anti-CD28 antibody. However, induction of IL-2 transcripts was observed only in thymocytes triggered jointly by the anti-CD2 combination plus anti-CD28 antibodies. The double-negative (CD4-8-) or CD1+ thymocytes isolated by sorting or by panning were unresponsive to CD2/CD28 triggering. The same mitogenic signal could induce vigorous proliferation of thymocytes with a mature phenotype, i.e., CD3+CD4+ or CD3+CD8+ thymocytes. Immunofluorescence studies demonstrated that the majority of CD3+ thymocytes were CD28+, and most of the CD28+ cells were located in the medullary compartment of thymus. These results indicated that the T cell lineage surface molecules CD28 and CD2 are involved in the regulation of expansion and further differentiation of mature thymocytes.
Transforming growth factor- as a differentiating factor for cultured smooth muscle cells
Authors: J. P. Gawaziuk, X. Ma, F. Sheikh, Z-Q. Cheng, P. A. Cattini, N. L. Stephens
Journal: European Respiratory Journal (2007)

The aim of the present study was to determine whether the development of supercontractile smooth muscle cells, contributing to the nonspecific hyperreactivity of airways in asthmatic patients, is due to transforming growth factor (TGF)-β. In cultured smooth muscle cells starved by removal of 10% foetal bovine serum for 7 days, growth arrest was seen; 30% became elongated and demonstrated super contractility. Study of conditioned medium suggested that the differentiating factor was TGF-β. Sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) was carried out on conditioned medium from the arrested cells. Two protein bands were identified as matrix metalloproteinase (MMP)-2 and TGF-β1. To determine second messenger signalling by SMAD2, Western blotting and confocal microscopy were employed. Conditioned medium from arrested cultures showed the presence of MMP-2 and TGF-β1, as revealed by SDS–PAGE; 68- and 25-kDa bands were seen. Differentiation was confirmed by upregulation of marker proteins, smooth muscle type myosin heavy chain and myosin light chain kinase. Confirmation was obtained by downregulating these proteins with decorin treatment, which reduces the levels of active TGF-β and an adenoviral dominant-negative vector coding for a mutated type II TGF-β-receptor. Activation of second messenger signalling was demonstrated immunocytochemically by the presence of phosphorylated SMAD2 and SMAD4. Transforming growth factor-β is likely to be the differentiating factor responsible for the development of these supercontractile smooth muscle cells. The development of such cells in vivo after cessation of an asthmatic attack could contribute to the nonspecific hyperreactivity of airways seen in patients.
Management: Part I—Behaviour change, diet, and activity
Authors: Alison Avenell, Naveed Sattar, Mike Lean
Journal: BMJ (2006)

In the United Kingdom over 22% of the adult population is now obese, with multiple health problems related to a body mass index—weight (in kilograms) divided by height (in metres) squared—of 30 or higher. In England the national service frameworks for diabetes and coronary heart disease highlight the importance of helping patients who are obese. People continue to gain weight until their 50s and 60s, so 30-40% of older people will be obese, with chronic disease, mobility problems, and depression aggravated by obesity.

Obesity needs to be managed like any other chronic disease—with empathy and a non-judgmental professional attitude. Helping people to manage their weight is difficult and can be discouraging and time consuming for health professionals.

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Resources for health professionals



High relapse rates, apparent lack of effectiveness, and lack of training and resources are major obstacles. However, an increasing evidence base exists for the effective management of obesity. And resources for health professionals are also now available.

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Achievable weight change (95% confidence intervals) from meta-analyses of randomised controlled trials in adults



For people who are obese, long term low fat diets—together with increased physical activity and strategies to help modify their lifestyle—may prevent type 2 diabetes in those with impaired glucose tolerance and improve the control of hypertension and type 2 diabetes. These health benefits are seen with surprisingly small weight losses—5-10% sustained over a year or more, well within achievable goals for weight loss and despite some weight regain over subsequent years.

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Important factors to evaluate in patient's history



General strategies for helping a patient with a weight problem include agreeing an individual, realistic, weight loss goal, such as 5-10% over three to six months. Achieving this goal can help motivate success. Aim for weight loss initially, followed by a distinct strategy for weight maintenance. Provide ongoing support …
A systematic review of the effects of upper body warm-up on performance and injury
Authors: J Matt McCrary, Bronwen J Ackermann, Mark Halaki
Journal: British Journal of Sports Medicine (2015)

Purpose This systematic review was conducted to identify the impact of upper body warm-up on performance and injury prevention outcomes. Methods Web of Science, MEDLINE, SPORTDiscus, PsycINFO and Cochrane databases were searched using terms related to upper extremity warm-up. Inclusion criteria were English language randomised controlled trials from peer-reviewed journals in which investigation of upper body warm-up on performance and injury prevention outcomes was a primary aim. Included studies were assessed for methodological quality using the PEDro scale. A wide variety of warm-up modes and outcomes precluded meta-analysis except for one group of studies. The majority of warm-ups were assessed as having ‘positive’, ‘neutral’, ‘negative’ or ‘specific’ effects on outcomes. Results Thirty-one studies met the inclusion criteria with 21 rated as having ‘good’ methodological quality. The studies investigated a total of 25 warm-up modes and 43 outcome factors that could be grouped into eight mode and performance outcome categories. No studies of upper body warm-up effects on injury prevention were discovered. Conclusions Strong research-based evidence was found for the following: high-load dynamic warm-ups enhance power and strength performance; warm-up swings with a standard weight baseball bat are most effective for enhancing bat speed; short-duration static stretching warm-up has no effect on power outcomes; and passive heating/cooling is a largely ineffective warm-up mode. A clear knowledge gap in upper body warm-up literature is the lack of investigation of injury prevention outcomes.
Racemic Adrenaline and Inhalation Strategies in Acute Bronchiolitis
Authors: Håvard Ove Skjerven, Jon Olav Gjengstø Hunderi, Sabine Kristin Brügmann-Pieper, Anne Charlotte Brun, Hanne Engen, Leif Eskedal, Marius Haavaldsen, Bente Kvenshagen, Jon Lunde, Leif Bjarte Rolfsjord, Christian Siva, Truls Vikin, Petter Mowinckel, Kai-Håkon Carlsen, Karin C. Lødrup Carlsen
Journal: New England Journal of Medicine (2013)

Acute bronchiolitis in infants frequently results in hospitalization, but there is no established consensus on inhalation therapy--either the type of medication or the frequency of administration--that may be of value. We aimed to assess the effectiveness of inhaled racemic adrenaline as compared with inhaled saline and the strategy for frequency of inhalation (on demand vs. fixed schedule) in infants hospitalized with acute bronchiolitis.In this eight-center, randomized, double-blind trial with a 2-by-2 factorial design, we compared inhaled racemic adrenaline with inhaled saline and on-demand inhalation with fixed-schedule inhalation (up to every 2 hours) in infants (<12 months of age) with moderate-to-severe acute bronchiolitis. An overall clinical score of 4 or higher (on a scale of 0 to 10, with higher scores indicating more severe illness) was required for study inclusion. Any use of oxygen therapy, nasogastric-tube feeding, or ventilatory support was recorded. The primary outcome was the length of the hospital stay, with analyses conducted according to the intention-to-treat principle.The mean age of the 404 infants included in the study was 4.2 months, and 59.4% were boys. Length of stay, use of oxygen supplementation, nasogastric-tube feeding, ventilatory support, and relative improvement in the clinical score from baseline (preinhalation) were similar in the infants treated with inhaled racemic adrenaline and those treated with inhaled saline (P>0.1 for all comparisons). On-demand inhalation, as compared with fixed-schedule inhalation, was associated with a significantly shorter estimated mean length of stay--47.6 hours (95% confidence interval [CI], 30.6 to 64.6) versus 61.3 hours (95% CI, 45.4 to 77.2; P=0.01) - as well as less use of oxygen supplementation (in 38.3% of infants vs. 48.7%, P=0.04), less use of ventilatory support (in 4.0% vs. 10.8%, P=0.01), and fewer inhalation treatments (12.0 vs. 17.0, P<0.001).In the treatment of acute bronchiolitis in infants, inhaled racemic adrenaline is not more effective than inhaled saline. However, the strategy of inhalation on demand appears to be superior to that of inhalation on a fixed schedule. (Funded by Medicines for Children; ClinicalTrials.gov number, NCT00817466; EudraCT number, 2009-012667-34.).
Prognostic factors in resected pathological N1-stage II nonsmall cell lung cancer
Authors: Chao-Yu Liu, Jung-Jyh Hung, Bing-Yen Wang, Wen-Hu Hsu, Yu-Chung Wu
Journal: European Respiratory Journal (2012)

Stage II nonsmall cell lung cancer (NSCLC) has been redefined in the seventh edition of tumour, node, metastasis (TNM) classification for lung cancer. Stages IIa and IIb both contain node-negative (N0) and node-positive (N1) subgroups. The aim of this study was to evaluate the prognostic factors for overall survival in patients with resected N1-stage II NSCLC. Between January 1992 and December 2010, we retrospectively reviewed the clinicopathological characteristics of 163 N1-stage II (T1a-T2bN1M0) NSCLC in patients undergoing curative resection as primary treatment. Median follow-up time was 37.2 months. The 1-, 3- and 5-yr overall survival rates were 85.3%, 62.1% and 43.5%, respectively. Tumour involvement of the hilar/interlobar nodal zone and poorly differentiated histological grade were significant predictors for worse overall survival using multivariate analysis (p = 0.001 and p = 0.015, respectively). There were trends toward worse overall survival in older patients and those with larger tumour size (p = 0.063 and p = 0.075, respectively). In resected N1-stage II NSCLC, hilar/interlobar nodal involvement and poorly differentiated histological grade were significant predictors of worse overall survival. The differences in survival between these subgroups of patients may lead to the use of different adjuvant therapies or post-surgical follow-up strategies.
The Prototoxin lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival In Vivo
Authors: Julie M. Miwa, Tanya R. Stevens, Sarah L. King, Barbara J. Caldarone, Ines Ibanez-Tallon, Cheng Xiao, Reiko Maki Fitzsimonds, Constantine Pavlides, Henry A. Lester, Marina R. Picciotto, Nathaniel Heintz
Journal: Neuron (2006)
Hodgkin's Disease in the United States: A Comparison of Patient Characteristics and Survival in the Centralized Cancer Patient Data System and the Surveillance, Epidemiology, and End Results Program&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Scott Davis, Steven Dahlberg, Max H. Myers, Amy Chen, Sandra C. Steinhorn
Journal: JNCI Journal of the National Cancer Institute (1987)

Demographic, pathologic, and clinical characteristics as well as subsequent survival were compared between 3,607 Hodgkin's disease (HD) patients registered by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute and 2,278 HD patients registered by comprehensive cancer centers (CCCs) belonging to the Centralized Cancer Patient Data System (CCPDS). All patients were diagnosed with HD between July 1977 and December 1982. CCPDS cases were slightly younger, more often of the nodular sclerosing histologic type, and presented with Stage II disease at diagnosis more often than did SEER cases. CCPDS and SEER cases were similar regarding the lymph node region of origin, sex, and race. The mortality rate among SEER patients was approximately 1.5 times that among CCPDS patients. This significant survival difference was observed within all stages and within all histologic subtypes and remained after controlling for the effects of age. Late-stage, older age, non-Caucasian race, and a more diffuse histologic appearance were all independent and significant predictors of poor survival. These findings suggest that the management of HD in CCCs results in improved outcome relative to that in the general population. Possible explanations for such effects are explored, and additional lines of pursuit are suggested.
Parenteral Nutrition With Branched–Chain Amino Acids in Hepatic Encephalopathy: Meta Analysis
Authors: Rebecca Dersimonian
Journal: Hepatology (1990)

The authors undertook a meta analysis of nine randomized clinical trials (RCTs) in which modified amino acid solutions that contained supplemental amounts of branched–chain amino acida (BCAA) were compared with other forms of therapy of hepatic encephalopathy (HE). When five RCTs were pooled, analysis showed highly significant improvement in the degree of HE (p &lt; 0.001). Various interpretations of the data gave similar reslts. The mortality data differed so widely in these RCTs that pooling of the data could not be meaningfully performed. In two RCTs BCAA therapy resulted in increased mortality, whereas in two others BCAA treatment was associated with increased survival. An aggregate relative risk reduction of 0.59 was calcilated with 95% confidence intervals of 0.23 to 0.80 (p &lt; 0.002). When the data from one additional study that had not yet been published and that showed BCAA therapy to be beneficial was added to the analysis, the pooled relative reduction was even greater i. e., 0.82 [p &lt; 0.0001]. The mortality in these studies was significantly reduced regardless of the type of statistical analysis performed (p = 0.023), Nevertheless, because of the short duration of follow–up in these studies and the striking differences in the effects of BCAA on mortality, the authors recommended that additional RCTs with prolonged follow–up be performed.
Gut intramucosal pH and intraluminal PO2 in a porcine model of peritonitis or haemorrhage.
Authors: J B Antonsson, U H Haglund
Journal: Gut (1995)

The tonometric method of detecting decreased gut intramucosal pH (pHi) is based on the fact that carbon dioxide can diffuse through the wall of the silastic balloon of the tonometer. By using deoxified saline and measuring PO2 as well as PCO2 this study aimed to follow changes in mucosal PO2 and relate them to changes in pHi in peritonitis versus haemorrhage. Twenty five pigs were used. Five were controls, in 10 peritonitis was induced by the instillation of faeces in the abdominal cavity, and 10 were bled, half of them stepwise during three hours, and half of them rapidly down to a mean (SEM) arterial pressure of 30 (10) mm Hg. The drop in pHi correlated well with decreasing intraluminal PO2 (r = 0.63 (0.13)) in haemorrhage. In peritonitis this drop occurred within a very limited change in intraluminal PO2 (r = 0.06 (0.17)). Thus oxygen seemed to be present in the mucosa at the same time as there were signs of anaerobic metabolism as evidenced by a low intramucosal pH. Impaired oxygen extraction or utilisation, or both, is proposed as an explanation to this seemingly paradoxical situation.