tbuckley/cabot-search huggingface dataset:
Zinc-α2-Glycoprotein Is Associated With Insulin Resistance in Humans and Is Regulated by Hyperglycemia, Hyperinsulinemia, or Liraglutide Administration
Authors: Mengliu Yang, Rui Liu, Shu Li, Yu Luo, Yali Zhang, Lili Zhang, Dongfang Liu, Yaxu Wang, Zhengai Xiong, Guenther Boden, Shirong Chen, Ling Li, Gangyi Yang
Journal: Diabetes Care (2012)

OBJECTIVE Zinc-α2-glycoprotein (ZAG) has been proposed to play a role in the pathogenesis of insulin resistance. Previous studies in humans and in rodents have produced conflicting results regarding the link between ZAG and insulin resistance. The objective of this study was to examine the relationships between ZAG and insulin resistance in cross-sectional and interventional studies. RESEARCH DESIGN AND METHODS Serum ZAG (determined with ELISA) was compared with various parameters related to insulin resistance in subjects with normal glucose tolerance, impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM), and in women with or without polycystic ovary syndrome (PCOS). Euglycemic-hyperinsulinemic clamps were performed in healthy and PCOS women. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of ZAG. The effect of a glucagon-like peptide-1 agonist on ZAG was studied in a 12-week liraglutide treatment trial. RESULTS Circulating ZAG was lower in patients with IGT and newly diagnosed T2DM than in controls. Circulating ZAG correlated positively with HDL cholesterol and adiponectin, and correlated inversely with BMI, waist-to-hip ratio, body fat percentage, triglycerides, fasting blood glucose, fasting insulin, HbA1c, and homeostasis model assessment of insulin resistance (HOMA-IR). On multivariate analysis, ZAG was independently associated with BMI, HOMA-IR, and adiponectin. ZAG mRNA and protein were decreased in adipose tissue of T2DM patients. Moreover, circulating ZAG levels were lower in women with PCOS than in women with high insulin sensitivity. Liraglutide treatment for 12 weeks significantly increased circulating ZAG levels. CONCLUSIONS We conclude that ZAG may be an adipokine associated with insulin resistance.
Evidence for the Renal Conversion of Angiotensin I in the Dog
Authors: W. G. FRANKLIN, M. J. PEACH, J. P. GILMORE
Journal: Circulation Research (1970)

Experiments were carried out on perfused canine kidneys in situ to determine if renal conversion of angiotensin I occurs. Various concentrations of decapeptide produced an immediate increase in renal vascular resistance when injected directly into the renal artery. Since the decapeptide is biologically inactive, the increased resistance was interpreted as indicating generation of angiotensin II. The extent of renal conversion of angiotensin I to angiotensin II was estimated to be approximately 19% in the normal dog. This percent conversion was reduced to about 10% in dogs maintained on high salt and DOCA for 7 to 10 days.
Middle East respiratory syndrome coronavirus: epidemic potential or a storm in a teacup?
Authors: Alimuddin I. Zumla, Ziad A. Memish
Journal: European Respiratory Journal (2014)

MERS coronavirus: potential pandemic or storm in a teacup?http://ow.ly/ttpkiThe Middle East respiratory syndrome (MERS) is a new killer respiratory disease caused by the MERS coronavirus (CoV) first reported from the Kingdom of Saudi Arabia (KSA) in September 2012, after identification of a novel betacoronavirus from a Saudi Arabian patient who died from a severe respiratory illness [1,2].Retrospective study of stored samples later showed that, earlier in April 2012, a cluster of severe respiratory illness occurred in a public health hospital in Zarqa, Jordan, where eight healthcare workers (HCWs) were among the 11 people affected, with two deaths attributed to .The appearance of any new fatal infectious disease, and uncertainty about its origin and mode of transmission, invariably threatens global health security and its detection in western countries rapidly focuses political and scientific attention.Unfortunately, at the same time, it evokes unnecessary and unwarranted fierce scientific competition and discourse, as was illustrated by the HIV, severe acute respiratory syndrome (SARS) and avian influenza epidemics [4][5][6][7][8].Disappointingly, the events surrounding the MERS-CoV have been no different [6].MERS-CoV was first isolated, sequenced and patented by Erasmus Medical Centre (EMC) researchers in Rotterdam, the Netherlands, and initially it was named after their centre as HCoV-EMC [2].Subsequently, international consensus led to renaming it as MERS-CoV [9].Since the first KSA case report in September 2012, the KSA Ministry of Health (MoH) has recommended mandatory testing for MERS-CoV in all cases of respiratory illness requiring intensive care admission.6 months after MERS-CoV was discovered, at the end of March 2013, there were only 17 MERS-CoV cases reported globally, nine of which were from KSA [10], four of these from one family case cluster [11].This small number of MERS-CoV cases would not have attracted much global attention had it not been for the high mortality rate in persons who contracted the disease, all of whom had medical comorbidities [9].Frenzied media reports followed the detection of MERS cases in the UK [11][12][13], France [14], Germany [15][16][17] and Italy [18], and focussed international attention.The media scaremongering and hype led to exaggerated claims of the potential threat of MERS-CoV to global health security.A flurry of scientific, political and media activity ensued, with global attention focussed on the pandemic potential of MERS-CoV.This had become particularly urgent and important in light of an estimated 2 million pilgrims from over 182 countries expected to visit Makkah and Madinah, KSA, to perform the
Fetal death as a result of placental immune reconstitution inflammatory syndrome
Authors: F. Caby, D. Lemercier, A. Coulomb, R. Grigorescu, L. Paris, F. Touafek, G. Carcelain, A. Canestri, M. Pauchard, C. Katlama, M. Dommergues, R. Tubiana
Journal: Journal of Infection (2010)
Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer
Authors: Sergio Kaiser, Young-Kyu Park, Jeffrey L Franklin, Richard B Halberg, Ming Yu, Walter J Jessen, Johannes Freudenberg, Xiaodi Chen, Kevin Haigis, Anil G Jegga, Sue Kong, Bhuvaneswari Sakthivel, Huan Xu, Timothy Reichling, Mohammad Azhar, Gregory P Boivin, Reade B Roberts, Anika C Bissahoyo, Fausto Gonzales, Greg C Bloom, Steven Eschrich, Scott L Carter, Jeremy E Aronow, John Kleimeyer, Michael Kleimeyer, Vivek Ramaswamy, Stephen H Settle, Braden Boone, Shawn Levy, Jonathan M Graff, Thomas Doetschman, Joanna Groden, William F Dove, David W Threadgill, Timothy J Yeatman, Robert J Coffey, Bruce J Aronow
Journal: Genome biology (2007)

Abstract Background The expression of carcino-embryonic antigen by colorectal cancer is an example of oncogenic activation of embryonic gene expression. Hypothesizing that oncogenesis-recapitulating-ontogenesis may represent a broad programmatic commitment, we compared gene expression patterns of human colorectal cancers (CRCs) and mouse colon tumor models to those of mouse colon development embryonic days 13.5-18.5. Results We report here that 39 colon tumors from four independent mouse models and 100 human CRCs encompassing all clinical stages shared a striking recapitulation of embryonic colon gene expression. Compared to normal adult colon, all mouse and human tumors over-expressed a large cluster of genes highly enriched for functional association to the control of cell cycle progression, proliferation, and migration, including those encoding MYC, AKT2, PLK1 and SPARC. Mouse tumors positive for nuclear β-catenin shifted the shared embryonic pattern to that of early development. Human and mouse tumors differed from normal embryonic colon by their loss of expression modules enriched for tumor suppressors (EDNRB, HSPE, KIT and LSP1). Human CRC adenocarcinomas lost an additional suppressor module (IGFBP4, MAP4K1, PDGFRA, STAB1 and WNT4). Many human tumor samples also gained expression of a coordinately regulated module associated with advanced malignancy (ABCC1, FOXO3A, LIF, PIK3R1, PRNP, TNC, TIMP3 and VEGF). Conclusion Cross-species, developmental, and multi-model gene expression patterning comparisons provide an integrated and versatile framework for definition of transcriptional programs associated with oncogenesis. This approach also provides a general method for identifying pattern-specific biomarkers and therapeutic targets. This delineation and categorization of developmental and non-developmental activator and suppressor gene modules can thus facilitate the formulation of sophisticated hypotheses to evaluate potential synergistic effects of targeting within- and between-modules for next-generation combinatorial therapeutics and improved mouse models.
Phylogenetic Network and Physicochemical Properties of Nonsynonymous Mutations in the Protein-Coding Genes of Human Mitochondrial DNA
Authors: J. S. Moilanen
Journal: Molecular Biology and Evolution (2003)

Theories on molecular evolution predict that phylogenetically recent nonsynonymous mutations should contain more non-neutral amino acid replacements than ancient mutations. We analyzed 840 complete coding-region human mitochondrial DNA (mtDNA) sequences for nonsynonymous mutations and evaluated the mutations in terms of the physicochemical properties of the amino acids involved. We identified 465 distinct missense and 6 nonsense mutations. 48% of the amino acid replacements changed polarity, 26% size, 8% charge, 32% aliphaticity, 13% aromaticity, and 44% hydropathy. The reduced-median networks of the amino acid changes revealed relatively few differences between the major continent-specific haplogroups, but a high variation and highly starlike phylogenies within the haplogroups. Some 56% of the mutations were private, and 25% were homoplasic. Nonconservative changes were more common than expected among the private mutations but less common among the homoplasic mutations. The asymptotic maximum of the number of nonsynonymous mutations in European mtDNA was estimated to be 1,081. The results suggested that amino acid replacements in the periphery of phylogenetic networks are more deleterious than those in the central parts, indicating that purifying selection prevents the fixation of some alleles.
Adalimumab for severe psoriasis and psoriatic arthritis: An open-label study in 30 patients previously treated with other biologics
Authors: Marina Papoutsaki, Maria-Sole Chimenti, Antonio Costanzo, Marina Talamonti, Arianna Zangrilli, Alessandro Giunta, Luca Bianchi, Sergio Chimenti
Journal: Journal of the American Academy of Dermatology (2007)
Parallel Pathways for Spectral Coding in Primate Retina
Authors: Dennis M. Dacey
Journal: Annual Review of Neuroscience (2000)

The primate retina is an exciting focus in neuroscience, where recent data from molecular genetics, adaptive optics, anatomy, and physiology, together with measures of human visual performance, are converging to provide new insights into the retinal origins of color vision. Trichromatic color vision begins when the image is sampled by short- (S), middle- (M) and long- (L) wavelength-sensitive cone photoreceptors. Diverse retinal cell types combine the cone signals to create separate luminance, red-green, and blue-yellow pathways. Each pathway is associated with distinctive retinal architectures. Thus a blue-yellow pathway originates in a bistratified ganglion cell type and associated interneurons that combine excitation from S cones and inhibition from L and M cones. By contrast, a red-green pathway, in which signals from L and M cones are opposed, is associated with the specialized anatomy of the primate fovea, in which the "midget" ganglion cells receive dominant excitatory input from a single L or M cone.
Results of percutaneous transluminal coronary angioplasty in women. 1985-1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty Registry.
Authors: S F Kelsey, M James, A L Holubkov, R Holubkov, M J Cowley, K M Detre
Journal: Circulation (1993)

BACKGROUND The National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) 1978-1981 Registry cohort indicated that PTCA risk was higher and efficacy was lower in women. Data from the 1985-1986 PTCA Registry are used to address the question of whether compared with men, women still have a worse outcome after PTCA. METHODS AND RESULTS The 1985-1986 NHLBI PTCA Registry collected data on consecutive, first-PTCA cases at 16 centers. Initial results are reported for 2,136 patients, 546 of whom were women. Four-year follow-up status was available on 95% of the cohort. Although women were an average of 4.5 years older than the male patients and had more cardiovascular risk factors and more severe angina, their coronary artery disease as assessed by angiography was not more extensive. Rates of angiographic success on a per-lesion basis were similar for women and men (89% versus 88%), and the clinical success rates (79%) were the same. Women had more initial complications (29% versus 20%, p &lt; 0.001) and a considerably higher procedural mortality rate (2.6% versus 0.3%, p &lt; 0.001). For patients who survived the initial procedure, 4-year survival was similar for men and women. At 4 years, women had slightly fewer events (myocardial infarction, repeat PTCA, and/or coronary artery bypass grafting). Despite the higher proportion of women reporting the presence of angina and medication use at 4 years, the proportion reporting improvement in symptomatic status was similar to that of men. CONCLUSIONS Women undergoing PTCA have a higher procedural mortality risk than men; this is explained in part by their worse cardiovascular risk factor profile. Otherwise, the success rate and long-term prognosis after PTCA are excellent, and PTCA should be considered for women in need of revascularization.
Hypercontractile Female Hearts Exhibit Increased <i>S</i> -Nitrosylation of the L-Type Ca <sup>2+</sup> Channel α1 Subunit and Reduced Ischemia/Reperfusion Injury
Authors: Junhui Sun, Eckard Picht, Kenneth S. Ginsburg, Donald M. Bers, Charles Steenbergen, Elizabeth Murphy
Journal: Circulation Research (2006)

Mechanisms underlying gender differences in cardiovascular disease are poorly understood. We found previously that, under hypercontractile conditions, female hearts exhibit significantly less ischemia/reperfusion injury than males. Here we show that male wild-type (WT) mouse hearts pretreated with 10 nmol/L isoproterenol before ischemia exhibited increased injury versus female hearts, but this relative protection in females was absent in eNOS(-/-) and nNOS(-/-) hearts. In isoproterenol-treated female versus male hearts, there was also more endothelial NO synthase (eNOS) associated with cardiomyocyte caveolin-3, and more neuronal NOS (nNOS) translocation to caveolin-3 during ischemia/reperfusion. S-nitrosothiol (SNO) formation was increased in isoproterenol-treated ischemic/reperfused hearts in all mouse genotypes, but only in WT mice was SNO content significantly higher in females than males. Using the biotin switch method, we identified the L-type Ca2+ channel alpha1 subunit as the predominant S-nitrosylated protein in membrane fractions, and following isoproterenol and ischemia/reperfusion male/female differences in SNO were seen only in WT hearts, but not in constitutive NOS(-/-) genotypes. The isoproterenol-induced increase in L-type Ca2+ current (ICa) was smaller in females versus in males, but NOS blockade increased ICa in females. This gender difference in ICa in isoproterenol-treated myocytes (and abolition on NOS inhibition) was mirrored exactly in Ca2+ transients and SR Ca2+ contents. In conclusion, these data suggest that eNOS and nNOS both play roles in the gender differences observed in ischemia/reperfusion injury under adrenergic stimulation, and also demonstrate increased S-nitrosylation of the L-type Ca2+ channels in female cardiomyocytes.
New horizons in gastroenterology: infection, inflammation, and immunity
Authors: M J G Farthing
Journal: Gut (2002)

Gastrointestinal diseases continue to have a major morbidity worldwide. Intestinal infections are the most common disorders of the gastrointestinal tract and infectious diarrhoeal disease continues to be a major cause of morbidity and mortality. Almost 5 million preschool children still die each year from infectious diarrhoea, either from dehydration and acidosis due to fluid losses or because of the direct effects of invasive micro-organisms on gut …
Angiotensin III Activates Nuclear Transcription Factor-κB in Cultured Mesangial Cells Mainly via AT2 Receptors
Authors: Óscar Lorenzo, Marta Ruiz-Ortega, Yusuke Suzuki, Mónica Rupérez, Vanesa Esteban, Takeshi Sugaya, Jesús Egido
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Nuclear factor-κB (NF-κB) regulates many genes involved in renal pathophysiologic processes. It was previously demonstrated that angiotensin II (AngII) and its amino-terminal degradation product AngIII activate NF-κB in mesangial cells. However, which are the Ang receptor subtypes involved in the NF-κB pathway and whether these Ang peptides act through the same or different receptors in mesangial cells have not been evaluated. Under the culture conditions used, quiescent rat mesangial cells expressed both AT 1 and AT 2 receptors. To investigate the receptors involved in the NF-κB pathway, two different approaches were used, i.e. , pharmacologic studies, using specific AT 1 and AT 2 receptor antagonists and agonists, and studies in AT 1 receptor-knockout mice. In cultured rat mesangial cells, both AT 1 and AT 2 receptor antagonists inhibited AngII-induced NF-κB DNA binding activity, whereas NF-κB activation elicited by AngIII was mainly blocked by the AT 2 receptor antagonist. Similar results were observed for cytosolic IκBα degradation. An AT 2 receptor agonist also activated NF-κB. In AT 1 receptor-knockout murine mesangial cells, AngIII and AngII increased NF-κB activity and degraded cytosolic IκBα; both processes were blocked by the AT 2 receptor antagonist. These data demonstrate that, in mesangial cells, NF-κB activation is mediated by AT 1 and AT 2 receptors, suggesting a novel intracellular signaling mechanism for AT 2 receptors in the kidney. Some differences in Ang peptide receptor-mediated responses were also observed. AngII activates NF-κB via AT 1 and AT 2 receptors, whereas AngIII acts mainly via AT 2 receptors. These results suggest the potential involvement of the AngIII/AT 2 receptor/NF-κB pathway in pathophysiologic processes in the kidney and provide a better understanding of the renin-angiotensin system.
Cigarette dependence: II. Doctor's role in management.
Authors: M A Russell
Journal: BMJ (1971)

A dependence disorder, once contracted, is as difficult to control in a society as it is to treat in an individual.The fact that cigarette smoking is pursued despite considerable health and financial disincentives points to the strength of the dependence.The Royal College of Physicians has recom- mended' that doctors "should set an example by still greater abstinence from smoking and must take every opportunity to urge their patients not to smoke cigarettes."Many doctors
On-demand anakinra treatment is effective in mevalonate kinase deficiency
Authors: E. J. Bodar, L. M. Kuijk, J. P. H. Drenth, J. W. M. van der Meer, A. Simon, J. Frenkel
Journal: Annals of the Rheumatic Diseases (2011)

Mevalonate kinase deficiency (MKD) is a hereditary autoinflammatory syndrome marked by recurrent attacks of fever and inflammation. Severe enzyme deficiency results in mevalonic aciduria (MA) and milder deficiency in hyperimmunoglobulin D syndrome (HIDS). Treatment remains a challenge.To observe the effect of the recombinant interleukin-1 receptor antagonist anakinra in patients with MKD.A prospective observational study was undertaken. Two patients with MA started continuous treatment with anakinra (1-2 mg/kg/day) and nine patients with HIDS chose between continuous treatment and on-demand treatment (starting at first symptoms of attack, 100 mg/day or 1 mg/kg/day for 5-7 days).Anakinra induced partial remission in one patient with MA but there was no response in the other patient with MA. In one patient with HIDS continuous treatment induced complete remission for 7 months but was stopped because of side effects. Eight patients with HIDS preferred on-demand treatment from the start. This induced a clinical response (≥50% reduction in duration) in 8 of 12 treated attacks without a change in attack frequency. Anakinra prevented fever attacks due to vaccination without inhibiting antibody induction. No major side effects were seen.On-demand treatment with anakinra in HIDS decreases the duration and severity of fever attacks. Because of the burden of daily injections and relatively long asymptomatic intervals of HIDS, all patients with HIDS preferred on-demand treatment.
Dependence receptor UNC5D mediates nerve growth factor depletion–induced neuroblastoma regression
Authors: Yuyan Zhu, Yuanyuan Li, Seiki Haraguchi, Meng Yu, Miki Ohira, Toshinori Ozaki, Atsuko Nakagawa, Toshikazu Ushijima, Eriko Isogai, Haruhiko Koseki, Yohko Nakamura, Cuize Kong, Patrick Mehlen, Hirofumi Arakawa, Akira Nakagawara
Journal: Journal of Clinical Investigation (2013)

Spontaneous regression of neuroblastoma (NB) resembles the developmentally regulated programmed cell death (PCD) of sympathetic neurons. Regressing tumor cells express high levels of the nerve growth factor (NGF) receptors TRKA and p75NTR and are dependent on NGF for survival; however, the underlying molecular mechanism remains elusive. Here, we show that UNC5D, a dependence receptor that is directly targeted by p53 family members, is highly expressed in favorable NBs. NGF withdrawal strongly upregulated UNC5D, E2F1, and p53 in human primary favorable NBs. The induced UNC5D was cleaved by caspases 2/3, and the released intracellular fragment translocated into the nucleus and interacted with E2F1 to selectively transactivate the proapoptotic target gene. The cleavage of UNC5D and its induction of apoptosis were strongly inhibited by addition of netrin-1. Unc5d(-/-) mice consistently exhibited a significant increase in dorsal root ganglia neurons and resistance to NGF depletion-induced apoptosis in sympathetic neurons compared with wild-type cells. Our data suggest that UNC5D forms a positive feedback loop with p53 and E2F1 to promote NGF dependence-mediated PCD during NB regression.