tbuckley/cabot-search huggingface dataset:
Screening and shouting about HCV
Authors: W ROSENBERG
Journal: Gut (2000)

See article on page 277 

In this month's Gut, Ward and colleagues1 report their study of the prevalence of hepatitis C virus (HCV) in women attending an inner London obstetric department (see page 277). The study was well designed and carefully executed. The methodology is valid and the findings are important. The authors make three key observations: that the prevalence of HCV in this population is high (0.8%); that uptake and acceptability of screening for HCV is good; and that many of the cases could not be identified by clinical criteria alone. Each of these findings is important in its own right. Together they reaffirm the importance of hepatitis C as a healthcare problem. They support the case for further investigation of screening strategies for HCV and suggest that antenatal screening should be considered carefully.

Accurate knowledge of the prevalence of a disease is particularly important when it is serious and treatable. In the 1970s the disease later recognised as hepatitis C was thought to be an inconsequential transaminitis that followed blood transfusion. Since the cloning of HCV in 1989, increasing knowledge of the natural history of hepatitis C has revealed a more serious outcome, at least for the minority of individuals who develop progressive fibrosis leading to cirrhosis, liver failure, and liver cancer.2 In the past year, effective treatment has been licensed3and even more effective therapies may follow. Now that more is known of the natural history of hepatitis C and the clinical and cost effectiveness of treatment, accurate knowledge of the true prevalence of HCV infection is very important for those plan- ning, funding, and delivering care to HCV infected individuals.

Early studies found …
Combined Heart Rate– and Accelerometer-Assessed Physical Activity Energy Expenditure and Associations With Glucose Homeostasis Markers in a Population at High Risk of Developing Diabetes
Authors: Anne-Louise S. Hansen, Bendix Carstensen, Jørn W. Helge, Nanna B. Johansen, Bibi Gram, Jens S. Christiansen, Søren Brage, Torsten Lauritzen, Marit E. Jørgensen, Mette Aadahl, Daniel R. Witte
Journal: Diabetes Care (2013)

Regular physical activity (PA) reduces the risk of developing type 2 diabetes, and different subtypes of dysglycemia have shown different associations with PA. To better understand the associations of PA and glucose homeostasis, we examined the association of objectively measured PA energy expenditure (PAEE) with detailed measures of glucose homeostasis.In 1,531 men and women, with low to high risk of developing type 2 diabetes, we measured 7 days of PAEE using a combined accelerometry and heart rate monitor (ActiHeart). Measures and indices of glucose homeostasis were derived from a 3-point oral glucose tolerance test in addition to measures of long-term glycemia (glycated hemoglobin A1c and advanced glycation end products). Associations of PAEE with glucose homeostasis markers were examined using linear regression models.Median age (IQR) was 66.6 years (62.1-71.6) (54% men) with a median ActiHeart wear time of 6.9 days (6.0-7.1) and PAEE level of 33.0 kJ/kg/day (23.5-46.1). In fully adjusted models, we found higher levels of PAEE to be positively associated with insulin sensitivity and negatively with insulin 2 h after glucose load (P<0.05).Even in an elderly population with low levels of PA, we found higher objectively measured PAEE levels to be associated with a more beneficial glucose metabolic profile. Although our findings are cross-sectional, they indicate that even without high-intensity exercise, increasing the overall level of PAEE slightly in an entire population at risk for developing type 2 diabetes may be a realistic and worthwhile goal to reach in order to achieve beneficial effect in terms of glucose metabolism.
The Change in Allograft Function among Long-Term Kidney Transplant Recipients
Authors: John S Gill, Marcello Tonelli, Christian H Mix, Brian J G Pereira
Journal: Journal of the American Society of Nephrology (2003)

Long-term kidney allograft survival continues to remain an elusive goal. Kidney transplant recipients are believed to be at high risk for loss of allograft function, and new, potentially non-nephrotoxic immunosuppressive medications are advocated to improve long-term allograft survival. To evaluate the efficacy of such therapeutic interventions, information regarding the change in GFR among kidney transplant recipients with long-term allograft survival is needed. We studied 40,963 transplant recipients between 1987 and 1996 with allograft survival of at least 2 yr in the United States Renal Data System. Linear regression methods were applied to serial GFR estimates after transplantation. The baseline mean GFR at 6 mo after transplantation was 49.6 ± 15.4 ml/min per 1.73 m2. During the mean follow-up of 5.7 ± 2.3 yr, the mean ± standard error of the change in GFR was −1.66 ± 6.51 ml/min per 1.73 m2 per year (median, −0.94 L/min per 1.73 m2 per year). A total of 12,583 (30%) of patients had improvement in GFR, 8133 (20%) patients had no change in GFR, and 20,247 (50%) patients had decline in GFR. It is concluded that, although most patients had significant impairment of GFR at baseline, the decline in GFR was slow and many patients had either no change or improvement in GFR. Strategies to improve long-term kidney allograft survival that increase baseline allograft function may be more effective than strategies to slow the decline in GFR. E-mail: bpereira@tufts-nemc.org
Increased SRF transcriptional activity in human and mouse skeletal muscle is a signature of insulin resistance
Authors: Wanzhu Jin, Allison B. Goldfine, Tanner Boes, Robert R. Henry, Theodore P. Ciaraldi, Eun-Young Kim, Merve Emecan, Connor Fitzpatrick, Anish Sen, Ankit Shah, Edward Mun, Martha Vokes, Joshua Schroeder, Elizabeth Tatro, Jose Jimenez-Chillaron, Mary-Elizabeth Patti
Journal: Journal of Clinical Investigation (2011)

Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) for which the molecular mediators remain unclear. We therefore conducted an expression analysis of human muscle biopsies from patients with T2D; normoglycemic but insulin-resistant subjects with a parental family history (FH(+)) of T2D; and family history-negative control individuals (FH(–)). Actin cytoskeleton genes regulated by serum response factor (SRF) and its coactivator megakaryoblastic leukemia 1 (MKL1) had increased expression in T2D and FH(+) groups. Furthermore, striated muscle activator of Rho signaling (STARS), an activator of SRF, was upregulated in T2D and FH(+) and was inversely correlated with insulin sensitivity. Skeletal muscle from insulin-resistant mice recapitulated this gene expression pattern and showed reduced G-actin and increased nuclear localization of MKL1, each of which regulates SRF activity. Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation, whereas reduction of STARS expression increased insulin signaling and glucose uptake. Pharmacological SRF inhibition by CCG-1423 reduced nuclear MKL1 and improved glucose uptake and tolerance in insulin-resistant mice in vivo. Thus, SRF pathway alterations are linked to insulin resistance, may contribute to T2D pathogenesis, and could represent therapeutic targets.
Prevention of diabetes in BioBreeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells.
Authors: A A Like, C A Biron, E J Weringer, K Byman, E Sroczynski, D L Guberski
Journal: The Journal of Experimental Medicine (1986)

Diabetes-prone BioBreeding/Worcester (BB/Wor) rats received thrice weekly injections of mAb against antigens expressed on the surface of all T cells (OX19), cytotoxic/suppressor, and NK cells (OX8), helper/inducer cells (W3/25, OX35, OX38), and Ia+ cells (OX6, 3JP, OX17). Treatment with OX8 or OX19 achieved stable reductions of splenic and peripheral blood NK cells and helper/inducer T lymphocytes, respectively, and protected against diabetes. OX19 injections also prevented lymphocytic insulitis, thyroiditis, and the synthesis of autoantibodies to thyroid colloid and smooth muscle antigens. OX8 injections reduced splenic NK-mediated YAC-1 cell lysis, but did not prevent insulitis, thyroiditis, or autoantibody synthesis. Injections of mAb specific for antigens on the surface of helper/inducer cells, and for cells expressing IaE antigens provided marginal protection against diabetes without reductions of phenotypic subsets. These findings suggest that pancreatic beta cell destruction in the spontaneously diabetic BB/Wor rat is mediated by the combined action of NK and helper/inducer cells.
Immune combinational therapy targeting OX40 and IDO synergistically enhances efficacy of a cancer vaccine
Authors: Zuzana Berrong, Shamim Ahmad, Rasha Abu Eid, Abdeljabar El Andaloussi, Tanusree Sen, Ross Stewart, Scott A Hammond, Rajeev Shrimali, Mikayel Mkrtichyan, Samir N Khleif
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Enhancing an effector immune response by cancer vaccines has not been clinically successful so far. Although the necessary immune response may be elicited using vaccine-based therapies, this has not been sufficient for a positive clinical outcome; since most cancers can escape
Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicentre, double-blind, placebo-controlled randomised trial
Authors: Maarten MJ van Eijk, Kit CB Roes, Marina LH Honing, Michael A Kuiper, Attila Karakus, Mathieu van der Jagt, Peter E Spronk, Willem A van Gool, Roos C van der Mast, Jozef Kesecioglu, Arjen JC Slooter
Journal: The Lancet (2010)
Marathon volleyball: changes after 61 hours play.
Authors: P M Lund
Journal: British Journal of Sports Medicine (1985)

A description of symptoms after long-standing physical activity has been the purpose of this study. Twelve healthy, well trained young men who participated in a marathon volleyball game were interviewed and examined 1 day, 1 week and 5 weeks after the game, which lasted 61 hours, 23 mins. During the game, and on the day after, different psychological symptoms appeared. These had all disappeared by the second day. Somatic symptoms were dominated by over-strain injuries to the locomotor system. At the first, second and third examinations the total number of injuries were 29, 26 and 9 respectively. These symptoms were diminishing in spite of continued physical activity and it is suggested that over-strain injuries might be sufficiently treated by moderate activity instead of recommending a period of total cessation from sports activities.
Are seat belt restraints as effective in school age children as in adults? A prospective crash study
Authors: S. I Halman
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To study effectiveness of seat belts for protecting school age children in road vehicle crashes. <b>Design:</b> Crash examinations by trained investigators. <b>Setting:</b> Ten Canadian university based crash investigation centres. <b>Subjects:</b> 470 children aged 4-14 years, with 168 selected for detailed analysis, and 1301 adults. <b>Main outcomes measures:</b> Use of seat belts by vehicle occupants; severity of injury adjusted for age and crash severity. <b>Results:</b> Overall, 40% (189/470) of children were unbelted. Of the 335 children in cars driven by belted adults, 73 (22%) were unbelted. The odds of sustaining fatal or moderately severe injury (injury severity score ≥4) for children in the front passenger seat was more than nine times higher for unbelted children than for belted ones (odds ratio 9.8 (95% confidence interval 2.4 to 39.4)) and for those in the rear left seat was more than two times higher for unbelted than for belted children (2.6 (1.1 to 5.9)). The protection afforded by seat belts compared favourably with the results for adults in the same seat positions (odds ratios for unbelted <i>v</i> belted adults of 2.4 and 2.7 for front and rear seat passengers respectively). <b>Conclusions:</b> Seat belts helped to protect school age children from injury in road vehicle crashes. However, 40% of children were unbelted. Despite standard seat belts being designed for adults, school age children were at least as well protected as adults. <h3>What is already known on this topic</h3> Although child restraints protect young children in road vehicle crashes, it is not known whether standard seat belts used by school age children work as well School age children are often unbelted in cars <h3>What this study adds</h3> Data from detailed crash assessments indicate that seat belts protected children at least as well as adults Adults were more likely than children to be belted, and 22% of children travelling with belted drivers were unbelted
Rapid reduction of methemoglobin in rat bone marrow erythroid cells
Authors: Toshitsugu Yubisui, Masazumi Takeshita, Donald E. Hultquist
Journal: American Journal of Hematology (1990)

Abstract Methemoglobin reduction was shown to proceed much more rapidly in erythroid cells from rat bone marrow than in rat erythrocytes. Methemoglobin reduction in suspensions of intact, nitrite‐treated bone marrow cells does not depend on the presence of glucose in the incubation mixture, even after the cells have been stored in substrate‐free medium. 2‐Deoxyglucose and iodoacetate prevent the reduction from proceeding to completion. The results suggest that, relative to erythrocytes, immature erythroid cells more efficiently catalyze methemoglobin reduction and more effectively store metabolites which provide electrons for this reaction.
Arsenic exposure from drinking water and dyspnoea risk in Araihazar, Bangladesh: a population-based study
Authors: Gene R. Pesola, Faruque Parvez, Yu Chen, Alauddin Ahmed, Rabiul Hasan, Habibul Ahsan
Journal: European Respiratory Journal (2011)

Bangladesh has high well water arsenic exposure. Chronic arsenic ingestion may result in diseases that manifest as dyspnoea, although information is sparse. Baseline values were obtained from an arsenic study. Trained physicians ascertained data on dyspnoea among 11,746 subjects. Data were collected on demographic factors, including smoking, blood pressure and arsenic exposure. Logistic regression models estimated odds ratios and confidence intervals for the association between arsenic exposure and dyspnoea. The adjusted odds of having dyspnoea was 1.32-fold (95% CI 1.15–1.52) greater in those exposed to high well water arsenic concentrations (≥50 μg·L −1 ) compared with low-arsenic-exposed nonsmokers (p&lt;0.01). A significant dose–response relationship was found for arsenic (as well as smoking) in relation to dyspnoea. In nonsmokers, the adjusted odds of having dyspnoea were 1.36, 1.96, 2.34 and 1.80-fold greater for arsenic concentrations of 7–38, 39–90, 91–178 and 179–864 μg·L −1 , respectively, compared with the reference arsenic concentration of &lt;7 μg·L −1 (p&lt;0.01; Chi-squared test for trend). Arsenic exposure through well water is associated with dyspnoea, independently of smoking status. This study suggests that mandated well water testing for arsenic with reduction in exposure may significantly reduce diseases that manifest as dyspnoea, usually cardiac or pulmonary.
Relationship of portal pressure, anorectal varices and hemorrhoids in cirrhotic patients
Authors: Teh-Fang Wang, Fa-Yauh Lee, Yang-Te Tsai, Shou-Dong Lee, Sun-Sang Wang, Hsiao-Chung Hsia, Wen-Jeh Lin, Han-Chieh Lin, Kwok-Hung Lai, Cho-Yu Chan, Kwang-Juei Lo
Journal: Journal of Hepatology (1992)
Tissue Inhibitor of Metalloproteinase-1 Protects Human Breast Epithelial Cells from Extrinsic Cell Death: A Potential Oncogenic Activity of Tissue Inhibitor of Metalloproteinase-1
Authors: Xu-Wen Liu, Marcus E. Taube, Ki-Kyung Jung, Zhong Dong, Yong J. Lee, Stefanie Roshy, Bonnie F. Sloane, Rafael Fridman, Hyeong-Reh Choi Kim
Journal: Cancer Research (2005)

Abstract Tissue inhibitors of metalloproteinases (TIMPs) inhibit matrix metalloproteinases and some members of a disintegrin and metalloproteinase domain (ADAM) family. In addition, recent studies unveiled novel functions of TIMPs in the regulation of apoptosis. TIMP-1 inhibits intrinsic apoptosis by inducing TIMP-1 specific cell survival pathways involving focal adhesion kinase (FAK). TIMP-3, however, was shown to enhance extrinsic cell death by inhibiting the shedding of the cell surface death receptors mediated by tumor necrosis factor-α converting enzymes (TACE/ADAM-17). Here, we examined whether TIMP-1, an inhibitor of some of the ADAM family members, enhances the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)–induced extrinsic apoptotic pathway. Surprisingly, we found that TIMP-1 effectively protects human breast epithelial cells from TRAIL-induced apoptosis, demonstrating opposite roles of TIMP-1 and TIMP-3 for the regulation of extrinsic apoptosis. TIMP-1 inhibition of TRAIL-induced apoptosis does not depend on its ability to inhibit matrix metalloproteinases or ADAM activities and is unrelated to its ability to stabilize active or decoy death receptors. Importantly, inhibition of PI 3-kinase signaling by wortmannin and down-regulation of FAK expression using siRNA significantly diminish TIMP-1 protection of human breast epithelial cells against TRAIL-induced extrinsic apoptosis. In addition, the in vitro three-dimensional culture studies showed that TIMP-1 inhibits lumen formation and apoptosis during morphogenesis of MCF10A acini. Taken together, these studies suggest that TIMP-1 may exert oncogenic activity in breast cancer through inhibition of both intrinsic and extrinsic apoptosis involving the FAK survival signal transduction pathway.
Glial Cell Line–Derived Neurotrophic Factor and Its Receptor Ret Is a Novel Ligand-Receptor Complex Critical for Survival Response during Podocyte Injury
Authors: Cynthia C. Tsui, Stuart J. Shankland, Brian A. Pierchala
Journal: Journal of the American Society of Nephrology (2006)

Glomerulosclerosis correlates with a reduction in podocyte number that occurs through mechanisms that include apoptosis. Whether glial cell line-derived neurotrophic factor (GDNF), a growth factor that is critical for neural and renal development, is a survival factor for injured podocytes was investigated. Ret, the GDNF receptor tyrosine kinase, was upregulated in podocytes in the passive Heymann nephritis and puromycin aminonucleoside (PA) nephrosis rat models of podocyte injury. In addition, Ret mRNA and protein were upregulated in mouse podocytes in vitro after injury that was induced by sublytic C5b-9 and PA. GDNF, which also was induced during podocyte injury, inhibited significantly the apoptosis of podocytes that was induced by ultraviolet C irradiation. Knockdown of Ret expression by small interference RNA in podocytes exacerbated apoptosis that was induced by both ultraviolet C and PA. Ret knockdown, upon injury, decreased AKT phosphorylation, suggesting that the phosphoinositol-3 kinase/AKT pathway mediated the survival effect of GDNF on podocytes. Consistent with this hypothesis, the selective phosphoinositol-3 kinase inhibitor LY294002 blocked the survival-promoting effects of GDNF. In conclusion, GDNF is a novel podocyte survival factor. Furthermore, Ret is highly upregulated during podocyte injury in vitro and in vivo, suggesting that Ret activation is a critical adaptive response for podocyte remodeling and repair.
Effect of coronary hyperemia on Emax and oxygen consumption in blood-perfused rabbit hearts. Energetic consequences of Gregg's phenomenon.
Authors: Y Goto, B K Slinker, M M LeWinter
Journal: Circulation Research (1991)

To assess the relation between increases in contractile function and oxygen consumption (VO2) during increased coronary flow (Gregg's phenomenon), we measured the end-systolic pressure-volume relation and the relation between VO2 and left ventricular systolic pressure-volume area (PVA, a measure of total mechanical energy output) in blood-perfused, isovolumically contracting rabbit hearts during control and intracoronary adenosine infusion. During adenosine infusion at a constant perfusion pressure (93 +/- 11 mm Hg), coronary flow increased by 99 +/- 76% (p less than 0.01), and the slope of the end-systolic pressure-volume relation, Emax (ventricular contractility index), increased by 18 +/- 15% (p less than 0.01). When compared at the same left ventricular volume, PVA increased by 20 +/- 14% (p less than 0.01) and VO2 by 19 +/- 15% (p less than 0.01) with adenosine. The VO2-PVA relation was linear under each condition (both median r = 0.98). With increased coronary flow, the VO2-intercept of the VO2-PVA relation (unloaded VO2) increased by 22 +/- 18% (p less than 0.01) without a change in the slope; that is, a parallel upward shift was observed, indicating that the contractile efficiency (energy conversion efficiency of the contractile machinery) remained constant. These increases in Emax and unloaded VO2 were not eliminated by beta-adrenergic blockade with propranolol. We conclude that increased coronary flow with adenosine at a constant perfusion pressure augments both Emax and the nonmechanical energetic cost for excitation-contraction coupling and basal metabolism via nonadrenergic mechanisms, without changing contractile efficiency.
Postnatal Time Frame for Renal Vulnerability to Enalapril in Rats
Authors: GREGOR GURON, NIELS MARCUSSEN, ANNIKA NILSSON, BIRGITTA SUNDELIN, PETER FRIBERG
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Angiotensin-converting enzyme inhibition or angiotensin II type 1 receptor blockade in neonatal, but not in weaned, rats induces irreversible renal histologic abnormalities and an impaired urinary concentrating ability. The aim of the present study was to define the postnatal time frame when the rat kidney is vulnerable to an interruption of the renin-angiotensin system. Male Wistar rats received daily injections of enalapril (10 mg/kg, intraperitoneally) during different age intervals within 3 to 24 d of age. Fluid handling and urinary concentrating ability, renal function under pentobarbital anesthesia, and kidney histology using stereologic techniques were evaluated in adult rats. Enalapril treatment within 3 to 13 d after birth induced abnormalities in renal function and morphology long-term, whereas treatment initiated at 14 d of age did not. The main histologic alterations were papillary atrophy, and a reduction in the volume of tubular epithelial cells in association with an increase in the proportion of interstitium, throughout the cortex and outer medulla. Functionally, the predominant defect was an impairment in urinary concentrating ability, which correlated with the degree of papillary atrophy. In conclusion, the vulnerable age interval for the induction of irreversible renal abnormalities by enalapril was the first 13 d after birth in the rat. This postnatal time span coincides with the completion of nephrogenesis and a period of marked tubular growth and differentiation, suggesting a pivotal role for angiotensin II in these processes.
Sickle Cell Biomechanics
Authors: Gilda A. Barabino, Manu O. Platt, Dhananjay K. Kaul
Journal: Annual Review of Biomedical Engineering (2010)

As the predominant cell type in blood, red blood cells (RBCs) and their biomechanical properties largely determine the rheological and hemodynamic behavior of blood in normal and disease states. In sickle cell disease (SCD), mechanically fragile, poorly deformable RBCs contribute to impaired blood flow and other pathophysiological aspects of the disease. The major underlying cause of this altered blood rheology and hemodynamics is hemoglobin S (HbS) polymerization and RBC sickling under deoxygenated conditions. This review discusses the characterization of the biomechanical properties of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology of the disease.