tbuckley/cabot-search huggingface dataset:
Association of Polymorphisms of the Apolipoprotein(a) Gene With Lipoprotein(a) Levels and Myocardial Infarction
Authors: Stephan R. Holmer, Christian Hengstenberg, Hans-Georg Kraft, Björn Mayer, Melanie Pöll, Susanne Kürzinger, Marcus Fischer, Hannelore Löwel, Gernot Klein, Günter A.J. Riegger, Heribert Schunkert
Journal: Circulation (2003)

Background— Serum lipoprotein(a) [Lp(a)] concentration is largely determined by variability at the apolipoprotein(a) gene locus. Most prominent effects relate to polymorphisms in the promoter (a pentanucleotide [PN] repeat) and coding regions (a kringle IV [K4] repeat), the latter of which also affects Lp(a) particle size. The impact of these polymorphisms on cardiovascular risk is poorly understood. Methods and Results— We studied both polymorphisms and Lp(a) levels in 834 registry-based myocardial infarction (MI) patients (38% women) and 1548 population-based controls. Lp(a) concentrations were inversely related with the numbers of K4 and PN repeats. However, the effect of the PN polymorphism was restricted to subjects producing small Lp(a) particles (≤8 PN 66.1 mg/dL versus &gt;8 PN 8.7 mg/dL; P &lt;0.0001). The odds to present with MI were elevated in individuals producing small Lp(a) particles (≤22 K4 repeats; OR 1.47 for men and 1.69 for women; P &lt; 0.002) and in women with ≤8 PN repeats (OR 1.46, P =0.009). Interestingly, in women, the frequent haplotype with ≤8 PN and ≤22 K4 repeats, which is related to high levels of small Lp(a) particles, resulted in an elevated OR for MI (1.79; P =0.01) independently of Lp(a) serum concentration. Conclusions— The K4 and PN repeat polymorphisms largely explain the high variability of serum Lp(a) levels. A haplotype with ≤8 PN and ≤22 K4 repeats is characterized by high concentrations of small Lp(a) particles. Our observation that this haplotype was associated with MI independently of Lp(a) serum levels may suggest that Lp(a) particle size in addition to its concentration may modulate MI risk in women.
Morphological, structural and biophysical properties of French and Brazilian photoaged skin
Authors: D.G. Mercurio, R. Jdid, F. Morizot, P. Masson, P.M.B.G. Maia Campos
Journal: British Journal of Dermatology (2015)

Summary Background Knowledge of skin biology and its alterations in different populations is very important for the development of appropriate skincare strategies. Objectives To evaluate and compare morphological, structural and biophysical properties of photoaged skin in French and Brazilian populations, using biophysical and skin-imaging techniques. Methods Forty-one French and 41 Brazilian healthy, female volunteers aged between 40 and 65 years were enrolled. Each participant completed a questionnaire concerning habits related to cosmetic use, sun exposure and sun protection during different life periods. Skin on the face and volar forearm was evaluated using noninvasive techniques, to determine skin colour, transepidermal water loss (TEWL), stratum corneum water content, skin microrelief, skin viscoelasticity and dermis structure. Reflectance confocal microscopy was used to measure epidermal layer thickness and epidermal morphological and structural characteristics. Results Compared with Brazilian skin, French skin was more hydrated, had a lower TEWL and presented a distinct viscoelastic profile on the forearms and face. Brazilian facial skin was more wrinkled, and the dermis was less echogenic on the forearms and face. The French participants had thicker stratum corneum. Brazilian facial skin presented a higher prevalence of rete ridge effacement, low interkeratinocyte reflectance, huddled collagen and solar elastosis. Conclusions Morphological, structural and biophysical differences were found when assessing the skin of the Brazilian and French participants, who were exposed to different environmental factors.
HIF-1–dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia
Authors: Holger K. Eltzschig, Parween Abdulla, Edgar Hoffman, Kathryn E. Hamilton, Dionne Daniels, Caroline Schönfeld, Michaela Löffler, German Reyes, Michael Duszenko, Jorn Karhausen, Andreas Robinson, Karen A. Westerman, Imogen R. Coe, Sean P. Colgan
Journal: The Journal of Experimental Medicine (2005)

Extracellular adenosine (Ado) has been implicated as central signaling molecule during conditions of limited oxygen availability (hypoxia), regulating physiologic outcomes as diverse as vascular leak, leukocyte activation, and accumulation. Presently, the molecular mechanisms that elevate extracellular Ado during hypoxia are unclear. In the present study, we pursued the hypothesis that diminished uptake of Ado effectively enhances extracellular Ado signaling. Initial studies indicated that the half-life of Ado was increased by as much as fivefold after exposure of endothelia to hypoxia. Examination of expressional levels of the equilibrative nucleoside transporter (ENT)1 and ENT2 revealed a transcriptionally dependent decrease in mRNA, protein, and function in endothelia and epithelia. Examination of the ENT1 promoter identified a hypoxia inducible factor 1 (HIF-1)–dependent repression of ENT1 during hypoxia. Using in vitro and in vivo models of Ado signaling, we revealed that decreased Ado uptake promotes vascular barrier and dampens neutrophil tissue accumulation during hypoxia. Moreover, epithelial Hif1α mutant animals displayed increased epithelial ENT1 expression. Together, these results identify transcriptional repression of ENT as an innate mechanism to elevate extracellular Ado during hypoxia.
Agonist-specific regulation of monocyte chemoattractant protein-1 expression by cyclooxygenase metabolites in hepatic stellate cells
Authors: E Efsen
Journal: Hepatology (2001)

Activated hepatic stellate cells (HSC) regulate the liver "wound-healing" response through expression of chemokines, including monocyte chemoattractant protein-1 (MCP-1), which participate in the formation of the inflammatory infiltrate during liver injury. Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid into prostaglandins, which may contribute to the inflammatory response. In this study, we investigated the effects of COX inhibitors on the expression of MCP-1 in cultured HSC. Pretreatment of HSC with nonspecific COX inhibitors such as indomethacin or ibuprofen markedly reduced the expression of MCP-1 caused by exposure to tumor necrosis factor α (TNF-α) or interleukin-1α (IL-1α). NS-398, a specific COX-2 inhibitor, also resulted in a dose-dependent inhibition of MCP-1 gene and protein expression. These effects were dependent on reduced MCP-1 transcription, as established using a reporter plasmid. In contrast, the up-regulation of MCP-1 expression caused by interferon gamma (IFN-γ) was not sensitive to COX inhibitors. Quiescent HSC did not show detectable expression of COX-2, which became evident after activation in culture, and while TNF-α and IL-1α markedly increased the expression of COX-2, IFN-γ did not have any effects. Pretreatment of HSC with the stable cyclic adenosine monophosphate (cAMP) analog, 8-bromo cAMP, reverted the effects of the COX-2 inhibitor, but not of a nuclear factor-κB (NF-κB) inhibitor, demonstrating that prostaglandins modulate MCP-1 expression via production of cAMP. On the other hand, the action of NF-κB inhibitors was negligible in IFN-γ—stimulated cells. These findings indicate that cross-talk between cytokines and a prostaglandin-cAMP pathway differentially regulates the proinflammatory potential of HSC, contributing to the modulation of liver tissue inflammation.
A Prospective Study to Compare Inhibitory Control Test (ICT) to a Psychometric Hepatic Encephalopathy Score (PHES) to Diagnose Minimal Hepatic Encephalopathy (MHE) and Determine Usefulness of ICT for the Diagnosis of MHE in the Indian Subcontinent as Well as to Correlate It With Severity of Underlying Liver Disease
Authors: Dhaval Gupta, Meghraj Ingle, Prabha Sawant
Journal: Clinical Gastroenterology and Hepatology (2014)
Effects of Typical, Atypical, and No Antipsychotic Drugs on Visual Contrast Detection in Schizophrenia
Authors: Yue Chen, Deborah L. Levy, Summer Sheremata, Ken Nakayama, Steven Matthysse, Philip S. Holzman
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Visual contrast detection has been reported in some studies to be normal in schizophrenia patients, but in other studies impairments have been reported. Because contrast detection in the visual processing system is mediated by dopamine, and because the pharmacotherapy of schizophrenia involves blocking dopamine postsynaptic receptor sites, the authors investigated the effects of dopamine-blocking antipsychotic drugs on visual contrast detection in schizophrenia. METHOD: Visual contrast detection thresholds were measured in healthy subjects and schizophrenia patients receiving typical and atypical antipsychotic drugs; a two-alternative, forced-choice psychophysical method was used. Also included were six patients receiving no antipsychotic treatment as well as clinically unaffected first-degree relatives of the schizophrenia patients. RESULTS: Patients receiving atypical antipsychotic drugs showed unimpaired visual contrast detection, those given typical antipsychotic drugs exhibited higher visual contrast detection thresholds, and the unmedicated schizophrenic patients showed visual contrast detection thresholds significantly below those of healthy subjects. CONCLUSIONS: Dopamine modulation via D2 receptor blockade affects sensory processes in schizophrenia, shifting visual contrast detection from hypersensitivity in the unmedicated state to normal and even to hyposensitive levels. Thus, antipsychotic drug treatment may account for the inconsistent reports concerning visual contrast detection in schizophrenia.
Amino Acid Transporter LAT3 Is Required for Podocyte Development and Function
Authors: Yuji Sekine, Yukino Nishibori, Yoshihiro Akimoto, Akihiko Kudo, Noriko Ito, Daisuke Fukuhara, Ryota Kurayama, Eiji Higashihara, Ellappan Babu, Yoshikatsu Kanai, Katsuhiko Asanuma, Michio Nagata, Årindam Majumdar, Karl Tryggvason, Kunimasa Yan
Journal: Journal of the American Society of Nephrology (2009)

LAT3 is a Na+-independent neutral l-amino acid transporter recently isolated from a human hepatocellular carcinoma cell line. Although liver, skeletal muscle, and pancreas are known to express LAT3, the tissue distribution and physiologic function of this transporter are not completely understood. Here, we observed that glomeruli express LAT3. Immunofluorescence, confocal microscopy, and immunoelectron microscopy revealed that LAT3 localizes to the apical plasma membrane of podocyte foot processes. In mice, starvation upregulated glomerular LAT3, phosphorylated AKT1, reconstituted the actin network, and elongated foot processes. In the fetal kidney, we observed intense LAT3 expression at the capillary loops stage of renal development. Finally, zebrafish morphants lacking lat3 function showed collapsed glomeruli with thickened glomerular basement membranes. Permeability studies of the glomerular filtration barrier in these zebrafish morphants demonstrated a disruption of selective glomerular permeability. Our data suggest that LAT3 may play a crucial role in the development and maintenance of podocyte structure and function by regulating protein synthesis and the actin cytoskeleton.
EBM and CAM
Authors: David M Griffiths
Journal: Journal of the Royal Society of Medicine (2008)

How wonderful to have ‘Confusion in equal measure’,1 ‘Evidence-based medicine’2 and ‘How the public is being misled about complementary/alternative medicine’3 all published close together. A couple of years ago Ecas, a charity working with people with physical disabilities, did some work using aromatherapy on the long-stay wards of a hospital. I have no evidence to explain why it made people feel and sleep better; all I know is that the patients said they felt relaxed afterwards and they slept better. So it was not EBM.

However, we encouraged the NHS to use endowment funds, not public funds, to expand the service as it made patients feel better. The response from the medical profession was depressing and contradicts Edzard Ernst's assertion that there is no evidence that the establishment wishes to suppress CAM. An FRS, no less, wrote to a national paper thus ‘Of course some people will be cheered up by nice smells, but where do you stop? I expect some people would love Chanel Number 5 on the NHS too.’ And from a Consultant Clinical Scientist, ‘The truth is that virtually no scientists believe aromatherapy works, because the evidence does not exist’ and ‘I do not doubt for a moment that having one's feet massaged is a distraction from the effects of illness, in which case let us admit court jesters to the wards’. Hardly ringing endorsements from the professionals.
Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31
Authors: Philomena Mburu, Mirna Mustapha, Anabel Varela, Dominique Weil, Aziz El-Amraoui, Ralph H Holme, Andreas Rump, Rachel E Hardisty, Stéphane Blanchard, Roney S Coimbra, Isabelle Perfettini, Nick Parkinson, Ann-Marie Mallon, Pete Glenister, Mike J Rogers, Adam J Paige, Lee Moir, Jo Clay, Andre Rosenthal, Xue Zhong Liu, Gonzalo Blanco, Karen P Steel, Christine Petit, Steve D M Brown
Journal: Nature Genetics (2003)
Social Movements in Health
Authors: Theodore M. Brown, Elizabeth Fee
Journal: Annual Review of Public Health (2013)

Most public health practitioners know that public health has relied on biomedical advances and administrative improvements, but it is less commonly understood that social movements in health have also been sources of motivation for population health advances. This review considers the impacts of social movements focused on urban conditions and health, on the health of children, and on behavioral and substance-related determinants of health and illustrates how these movements have significantly influenced public health activities and programs. We hope this review will motivate public health workers to make common cause with social activists and to encourage social activists to ally with public health professionals.
Differential phosphorylation-dependent regulation of constitutively active and muscarinic receptor-activated IK,ACh channels in patients with chronic atrial fibrillation
Authors: N VOIGT, A FRIEDRICH, M BOCK, E WETTWER, T CHRIST, M KNAUT, R STRASSER, U RAVENS, D DOBREV
Journal: Cardiovascular Research (2007)

In chronic atrial fibrillation (cAF) the potassium current IK,ACh develops agonist-independent constitutive activity. We hypothesized that abnormal phosphorylation-dependent regulation underlies the constitutive IK,ACh activity.We used voltage-clamp technique and biochemical assays to study IK,ACh regulation in atrial appendages from 61 sinus rhythm (SR), 11 paroxysmal AF (pAF), and 33 cAF patients.Compared to SR basal current was higher in cAF only, whereas the muscarinic receptor (2 micromol/L carbachol)-activated IK,ACh was smaller in pAF and cAF. In pAF the selective IK,ACh blocker tertiapin abolished the muscarinic receptor-activated IK,ACh but excluded agonist-independent constitutive IK,ACh activity. Blockade of type-2A phosphatase and the subsequent shift to increased muscarinic receptor phosphorylation (and inactivation) reduced muscarinic receptor-activated IK,ACh in SR but not in cAF, pointing to an impaired function of G-protein-coupled receptor kinase. Using subtype-selective kinase inhibitors we found that in SR the muscarinic receptor-activated IK,ACh requires phosphorylation by protein kinase G (PKG), protein kinase C (PKC), and calmodulin-dependent protein kinase II (CaMKII), but not by protein kinase A (PKA). In cAF, constitutive IK,ACh activity results from abnormal channel phosphorylation by PKC but not by PKG or CaMKII, whereas the additional muscarinic receptor-mediated IK,ACh activation occurs apparently without involvement of these kinases. In cAF, the higher protein level of PKCepsilon but not PKCalpha, PKCbeta1 or PKCdelta is likely to contribute to the constitutive IK,ACh activity.The occurrence of constitutive IK,ACh activity in cAF results from abnormal PKC function, whereas the muscarinic receptor-mediated IK,ACh activation does not require the contribution of PKG, PKC or CaMKII. Selective drug targeting of constitutively active IK,ACh channels may be suitable to reduce the ability of AF to become sustained.
Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting.
Authors: A Frey, K T Giannasca, R Weltzin, P J Giannasca, H Reggio, W I Lencer, M R Neutra
Journal: The Journal of Experimental Medicine (1996)

Transepithelial transport of antigens and pathogens across the epithelial barrier by M cells may be a prerequisite for induction of mucosal immunity in the intestine. Efficient transport of antigens and pathogens requires adherence to M cell apical surfaces. Coupling of antigen-containing particles to the pentameric binding subunit of cholera toxin (CTB) has been proposed as a means for increasing antigen uptake because the CTB receptor, ganglioside GM1, is a glycolipid present in apical membranes of all intestinal epithelial cells. To test the accessibility of enterocyte and M cell membrane glycolipids to ligands in the size ranges of viruses, bacteria, and particulate mucosal vaccines, we analyzed binding of CTB probes of different sizes to rabbit Peyer's patch epithelium. Soluble CTB-fluorescein isothiocyanate (diameter 6.4 nm) bound to apical membranes of all epithelial cells. CTB coupled to 14 nm colloidal gold (final diameter, 28.8 nm) failed to adhere to enterocytes but did adhere to M cells. CTB-coated, fluorescent microparticles (final diameter, 1.13 microns) failed to adhere to enterocytes or M cells in vivo or to well-differentiated Caco-2 intestinal epithelial cells in vitro. However, these particles bound specifically to GM1 on BALB/c 3T3 fibroblasts in vitro and to undifferentiated Caco-2 cells that lacked brush borders and glycocalyx. Measurements of glycocalyx thickness by electron microscopy suggested that a relatively thin (20 nm) glycocalyx was sufficient to prevent access of 1-micron microparticles to glycolipid receptors. Thus, the barrier function of the intestinal epithelial cell glycocalyx may be important in limiting microbial adherence to membrane glycolipids, and in CTB-mediated targeting of vaccines to M cells and the mucosal immune system.
Blood Pressure Evaluation among Older Living Kidney Donors
Authors: Stephen C. Textor, Sandra J. Taler, Timothy S. Larson, Mikel Prieto, Matthew Griffin, James Gloor, Scott Nyberg, Jorge Velosa, Thomas Schwab, Mark Stegall
Journal: Journal of the American Society of Nephrology (2003)

With more patients reaching end-stage renal disease, the demand for living kidney donation is increasing rapidly. Many potential donors are now in older age groups. The effects of increasing BP with age and the measurement criteria for hypertension in this group are not well defined. A total of 238 potential donors between 18 and 72 yr of age were prospectively studied, with a comparison of "clinic" BP values measured in the outpatient clinic with an oscillometric recorder (Dinamap; Critikon), ambulatory BP monitoring (ABPM) findings, and standardized BP values determined by nurses using American Heart Association criteria. Renal function was evaluated on the basis of iothalamate clearance (GFR) and urinary protein and microalbumin excretion. Ninety-six percent of subjects were Caucasian. All subjects exhibited normal GFR and urinary protein excretion. Three age groups were defined (group I, </=35 yr, n = 64; group II, 36 to 49 yr, n = 109; group III, >/= 50 yr, n = 65). BP increased with age, as determined with all methods. Subjects >/= 50 yr of age exhibited the highest clinic readings (145 +/- 2/83 +/- 1 mmHg, compared with 129 +/- 2/76 +/- 1 mmHg for group I, P < 0.01). Awake ABPM and nurse-determined BP measurements were lower than clinic readings, including those for group III (131 +/- 2/80 +/- 1 mmHg, compared with 145 +/- 2/83 +/- 1 mmHg in the clinic, P < 0.001). With the use of systolic BP values of >140 mmHg and/or diastolic BP values of >90 mmHg, 36.7% of subjects were initially considered hypertensive; this proportion decreased to 11% overall with awake ABPM findings (>135/85 mmHg). Measurement variability (SD in ABPM) and the effects of misclassification were greatest for donors >/= 50 yr of age. Multivariate regression indicated that GFR of both donors and recipients decreased with age, but regression identified no independent effect of BP. Recipient outcomes for up to 2 yr were equally good for donor kidneys considered normotensive or hypertensive on the basis of clinic BP measurements. These data indicate that higher arterial BP with age can lead to misclassification of many older living kidney donors. Sixty-two subjects with excellent kidney function were misclassified as hypertensive with clinic oscillometric measurements alone. Detailed evaluations of ABPM findings, GFR, and urinary protein levels are warranted for Caucasian subjects with high clinic BP readings who are otherwise suitable potential donors.