tbuckley/cabot-search huggingface dataset:
Biogenesis of intestinal lactase-phlorizin hydrolase in adults with lactose intolerance. Evidence for reduced biosynthesis and slowed-down maturation in enterocytes.
Authors: E E Sterchi, P R Mills, J A Fransen, H P Hauri, M J Lentze, H Y Naim, L Ginsel, J Bond
Journal: Journal of Clinical Investigation (1990)

Enzymatic activity, biosynthesis, and maturation of lactasephlorizin hydrolase (LPH) were investigated in adult volunteers with suspected lactose intolerance. Mean LPH activity in jejunal biopsy homogenates of these individuals was 31% compared to LPH-persistent individuals, and was accompanied by a reduced level of LPH-protein. Mean sucrase activity in individuals with low LPH was increased to 162% and was accompanied by an increase in sucrase-isomaltase (SI)-protein. Biosynthesis of LPH, SI, and aminopeptidase N (APN) was studied in organ culture of small intestinal biopsy specimens. In individuals with LPH restriction, the rate of synthesis of LPH was drastically decreased, reaching just 6% of the LPH-persistent group after 20 h of culture, while the rate of synthesis of SI appeared to be increased. In addition, maturation of pro-LPH to mature LPH occurred at a slower rate in LPH-restricted tissue. Immunoelectron microscopy revealed an accumulation of immunoreactive LPH in the Golgi region of enterocytes from LPH-restricted individuals and reduced labeling of microvillus membranes. Therefore, lactose intolerance in adults is mainly due to a decreased biosynthesis of LPH, either at the transcriptional or translational level. In addition, intracellular transport and maturation is retarded in some of the LPH-restricted individuals, and this leads to an accumulation of newly synthesized LPH in the Golgi and a failure of LPH to reach the microvillus membrane.
Loss of Plakophilin-2 Expression Leads to Decreased Sodium Current and Slower Conduction Velocity in Cultured Cardiac Myocytes
Authors: Priscila Y. Sato, Hassan Musa, Wanda Coombs, Guadalupe Guerrero-Serna, Gustavo A. Patiño, Steven M. Taffet, Lori L. Isom, Mario Delmar
Journal: Circulation Research (2009)

Plakophilin-2 (PKP2) is an essential component of the cardiac desmosome. Recent data show that it interacts with other molecules of the intercalated disc. Separate studies show preferential localization of the voltage-gated sodium channel (Na(V)1.5) to this region.To establish the association of PKP2 with sodium channels and its role on action potential propagation.Biochemical, patch clamp, and optical mapping experiments demonstrate that PKP2 associates with Na(V)1.5, and that knockdown of PKP2 expression alters the properties of the sodium current, and the velocity of action potential propagation in cultured cardiomyocytes.These results emphasize the importance of intermolecular interactions between proteins relevant to mechanical junctions, and those involved in electric synchrony. Possible relevance to the pathogenesis of arrhythmogenic right ventricular cardiomyopathy is discussed.
<i>In vivo</i> Molecular Imaging of Cancer with a Quenching Near-Infrared Fluorescent Probe Using Conjugates of Monoclonal Antibodies and Indocyanine Green
Authors: Mikako Ogawa, Nobuyuki Kosaka, Peter L. Choyke, Hisataka Kobayashi
Journal: Cancer Research (2009)

Abstract Near-infrared (NIR) fluorophores have several advantages over visible fluorophores, including improved tissue penetration and lower autofluorescence; however, only indocyanine green (ICG) is clinically approved. Its use in molecular imaging probes is limited because it loses its fluorescence after protein binding. This property can be harnessed to create an activatable NIR probe. After cell binding and internalization, ICG dissociates from the targeting antibody, thus activating fluorescence. ICG was conjugated to the antibodies daclizumab (Dac), trastuzumab (Tra), or panitumumab (Pan). The conjugates had almost no fluorescence in PBS but became fluorescent after SDS and 2-mercaptoethanol, with a quenching capacity of 10-fold for 1:1 conjugates and 40- to 50-fold for 1:5 conjugates. In vitro microscopy showed activation within the endolysosomes in target cells. In vivo imaging in mice showed that CD25-expressing tumors were specifically visualized with Dac-ICG. Furthermore, tumors overexpressing HER1 and HER2 were successfully characterized in vivo by using Pan-ICG(1:5) and Tra-ICG(1:5), respectively. Thus, we have developed an activatable NIR optical probe that “switches on” only in target cells. Because both the antibody and the fluorophore are Food and Drug Administration approved, the likelihood of clinical translation is improved. [Cancer Res 2009;69(4):1268–72]
A randomized trial comparing primary infarct artery stenting with or without abciximab in acute myocardial infarction
Authors: David Antoniucci, Alfredo Rodriguez, Albrecht Hempel, Renato Valenti, Angela Migliorini, Federico Vigo, Guido Parodi, Carlos Fernandez-Pereira, Guia Moschi, Antonio Bartorelli, Giovanni Maria Santoro, Leonardo Bolognese, Antonio Colombo
Journal: Journal of the American College of Cardiology (2003)
STUDIES ON X-RAY EFFECTS
Authors: Waro Nakahara, James B. Murphy
Journal: The Journal of Experimental Medicine (1921)

Mice treated with small doses of x-rays and inoculated with cancer immediately afterwards, show a marked suppression of lymphoid proliferation. If, however, the cancer inoculation is made 7 days after the exposure to x-rays, thus permitting the primary lymphoid stimulation known to occur soon after the x-ray treatment to arise, a second stimulation takes place in a large proportion of mice thus inoculated. Changes in the blood of mice x-rayed and inoculated with cancer 7 days afterwards show that the state of resistance to cancer inoculation is attended by blood lymphocytosis, as is the case in all other varieties of immunity to transplanted cancer so far studied.
Individual Replacement Therapy (IRT) with a Pasteurized C1-Inhibitor Concentrate Compared to Prophylaxis with Danazol in Patients with Hereditary Angioedema (HAE) - A Prospective Study
Authors: I. Martinez-Saguer, E. Rusicke, E. Aygören-Pürsün, W. Kreuz
Journal: Journal of Allergy and Clinical Immunology (2006)
The effect of preseasonal immunotherapy on the production of histamine-refeasing factor (HRF) by mononuclear cells from patients with seasonal asthma: Results of a double-blind, placebo-controlled, randomized study
Authors: Piotr Kuna, Rafeul Alam, Beata Kuzminska, Jerzy Rozniecki
Journal: Journal of Allergy and Clinical Immunology (1989)
The great medicines scandal
Authors: Tessa Richards
Journal: BMJ (2006)

NHS Foundation Trust, the use of medicines committee has endorsed a policy of switching from atorvastatin 10 mg and 20 mg (no longer stocked) under new statin guidelines. 7 The first line statin is simvastatin 40 mg, which is substituted when a newly admitted patient has been taking atorvastatin 10 mg or 20 mg.If simvastatin is not tolerated or considered inappropriate, the alternative is pravastatin 40 mg, another cheap generic statin.This simple change will save the hospital trust £80 000 a year.However, most statins are prescribed in primary care.In at least three London primary care trusts partnerships with local general practitioners and systematic switching programmes are in place to realise large scale savings.These important local initiatives need to be replicated nationally to realise the full economic benefits of generic simvastatin, as has happened in some European countries, most notably Germany.It is time for the United Kingdom to implement therapeutic substitution of simvastatin 40 mg nationally by switching patients currently taking atorvastatin 10 mg and 20 mg, and prescribing generic simvastatin for new patients needing primary prevention of coronary heart disease.This policy would save £2bn, increase value for money, and release much needed resources to other areas of the NHS.
Cystathionine γ-lyase regulates arteriogenesis through NO-dependent monocyte recruitment
Authors: Gopi K. Kolluru, Shyamal C. Bir, Shuai Yuan, Xinggui Shen, Sibile Pardue, Rui Wang, Christopher G. Kevil
Journal: Cardiovascular Research (2015)

Aims: Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously produced in the vasculature by the enzyme cystathionine γ-lyase (CSE).However, the importance of CSE activity and local H2S generation for ischemic vascular remodeling remains completely unknown.In this study, we examine the hypothesis that CSE critically regulates ischemic vascular remodeling involving H2S dependent mononuclear cell regulation of arteriogenesis.Methods and results: Arteriogenesis including mature vessel density, collateral formation; blood flow and SPY angiographic blush rate were determined in WT and CSEKO mice at different time points following femoral artery ligation (FAL).The role of endogenous H2S in regulation of IL-16 expression and subsequent recruitment of monocytes, and expression of VEGF and bFGF in ischemic tissues, were determined along with EPC (CD34/Flk1) formation and function.FAL of wild type mice significantly increased CSE activity, expression and endogenous H2S generation in ischemic tissues and monocyte infiltration, which was absent in CSEKO mice.Treatment of CSEKO mice with the polysulfide donor diallyl trisulfide (DATS) restored ischemic vascular remodeling, monocyte infiltration and cytokine expression.Importantly, exogenous H2S therapy restored NO bioavailability in CSEKO mice that was responsible for monocyte recruitment and arteriogenesis.Conclusion: Endogenous CSE/H2S regulates ischemic vascular remodeling mediated during hind limb ischemia through NO dependent monocyte recruitment and cytokine induction revealing a previously unknown mechanism of arteriogenesis.
Congestive Heart Failure in the Community
Authors: Michele Senni, Christophe M. Tribouilloy, Richard J. Rodeheffer, Steven J. Jacobsen, Jonathan M. Evans, Kent R. Bailey, Margaret M. Redfield
Journal: Circulation (1998)

Data are limited regarding the classification and prognosis of patients with congestive heart failure (CHF) in the community.Using the resources of the Rochester Epidemiology Project, we evaluated all patients receiving a first diagnosis of CHF in Olmsted County, Minnesota, in 1991 (n=216). Among these patients, 88% were >/=65 years and 49% were >/=80 years of age. The prognosis of patients with a new diagnosis of CHF was poor; survival was 86+/-2% at 3 months, 76+/-3% at 1 year, and 35+/-3% at 5 years. Of the 216 patients, 137 (63%) had an assessment of ejection fraction. In these patients, systolic function was preserved (ejection fraction >/=50%) in 59 (43%) and reduced (ejection fraction <50%) in 78 (57%). Survival adjusted for age, sex, NYHA class, and coronary artery disease was not significantly different between patients with preserved and those with reduced systolic function (relative risk, 0.80; P=0.369). ACE inhibitors were used in only 44% of the total population with CHF.The present study reports the clinical characteristics and natural history of CHF as it presents in the community in the vasodilator era. CHF is a disease of the "very elderly," frequently occurs in the setting of normal ejection fraction, and has a poor prognosis, regardless of the level of systolic function. Diagnostic and therapeutic methods are underused in the community.
Prevalence of sleep disordered breathing in coeliac children
Authors: Gerarda Mastrogiorgio, Alessandro Ferretti, Nicoletta Pietropaoli, Jole Rabasco, Laura Petrarca, Matteo Florio, Marcherita Bonamico, Maria Pia Villa
Journal: European Respiratory Journal (2013)

Introduction   Coeliac disease (CD) is a chronic disease with a various clinical presentation. However sleep disordered breathing (SDB) has not yet been studied.   Aims and objectives   To evaluate the prevalence of SDB in a cohort of coeliac children at diagnosis and at least 6 months after starting gluten free diet (GFD).   Methods   We enrolled 74 children attending the our Pediatric Department and receiving a diagnosis of CD in the period 2010-2012. We included children without conditions that might lead to potential bias (obesity, congenital syndromes and undergoing pharmacological, orthodontic or surgical treatment). A medical SDB symptoms questionnaire was administered to parents of 66 coeliac children with inclusion criteria (62,1% female, age ranged 1-16 years; mean age 6,75±4). The questionnaire scored the SDB’s hallmark symptoms and identified four clusters of severity: 0-5 negative, 6-15 mild, 16-25 moderate, >25 severe.   Results   Five of 66 children (7,6%) showed a severe SDB and 14/66 (21,2%) a moderate SDB. A significant difference is present between mean scores of severe and moderate patients before and after GFD, respectively from 29,8±2,7 to 17,2±9,8 (p  The prevalence of key SDB symptoms at CD diagnosis is as follows: snoring 13,6%, apnea 10,6%, mouth-breathing 16,7%, restless sleep 25,8%, drowsiness 45,5% and diurnal restlessness 40,9%.   Conclusions   Our study demonstrates that SDB prevalence in coeliac children is higher than general population and the GFD is able to reduce it. Positive children to our questionnaire should be undergone polysomnographic recording to confirm the diagnosis and avoid the well-known complications of SDB.
Early peripheral muscle structural and metabolic impairment in chronic obstructive pulmonary disease (COPD) patients cannot be considered as a consequence of sedentarity
Authors: Fares Gouzi, Aldjia Abdellaoui, Sami Sedraoui, Thierry Lafontaine, Philippe DeRigal, Dalila Laoudj-Chenivesse, Jacques Mercier, Christian Préfaut, Maurice Hayot
Journal: European Respiratory Journal (2011)

Peripheral muscle dysfunction in COPD patients has been related to a muscle/fiber atrophy and oxidative metabolism reduction, which mimicks a severe disuse. Thus, we investigated the structure and mitochondrial function in skeletal muscle biopsies from patients with COPD and sedentary healthy subjects (SHS).  24 stage I-III (according to the GOLD classification) COPD patients and 21 age-matched SHS (  COPD patient and PA level-matched SHS (activity counts/day: 133±70 vs 135±48; p=0,9), had the same muscle mass and fiber cross-sectional areas. However, there was a reduction of the quadriceps endurance and of the type I fiber proportion (35% [28-49] vs 41% [38-53]; p  This study showed an early impairment of the muscle oxidative metabolism (type I fibers and mitochondrial efficiency), unexplained by the PA reduction in COPD patients and suggest that the oxidative phosphorylation alteration (OXPHOS pathway) occurs in the PHOS part, i.e. the ATP synthesis rate.
The Effects of Poverty on Childhood Brain Development
Authors: Joan Luby, Andy Belden, Kelly Botteron, Natasha Marrus, Michael P. Harms, Casey Babb, Tomoyuki Nishino, Deanna Barch
Journal: JAMA Pediatrics (2013)

IMPORTANCE The study provides novel data to inform the mechanisms by which poverty negatively impacts childhood brain development. OBJECTIVE To investigate whether the income-to-needs ratio experienced in early childhood impacts brain development at school age and to explore the mediators of this effect. DESIGN, SETTING, AND PARTICIPANTS This study was conducted at an academic research unit at the Washington University School of Medicine in St Louis. Data from a prospective longitudinal study of emotion development in preschool children who participated in neuroimaging at school age were used to investigate the effects of poverty on brain development. Children were assessed annually for 3 to 6 years prior to the time of a magnetic resonance imaging scan, during which they were evaluated on psychosocial, behavioral, and other developmental dimensions. Preschoolers included in the study were 3 to 6 years of age and were recruited from primary care and day care sites in the St Louis metropolitan area; they were annually assessed behaviorally for 5 to 10 years. Healthy preschoolers and those with clinical symptoms of depression participated in neuroimaging at school age/early adolescence. EXPOSURE Household poverty as measured by the income-to-needs ratio. MAIN OUTCOMES AND MEASURES Brain volumes of children's white matter and cortical gray matter, as well as hippocampus and amygdala volumes, obtained using magnetic resonance imaging. Mediators of interest were caregiver support/hostility measured observationally during the preschool period and stressful life events measured prospectively. RESULTS Poverty was associated with smaller white and cortical gray matter and hippocampal and amygdala volumes. The effects of poverty on hippocampal volume were mediated by caregiving support/hostility on the left and right, as well as stressful life events on the left. CONCLUSIONS AND RELEVANCE The finding that exposure to poverty in early childhood materially impacts brain development at school age further underscores the importance of attention to the well-established deleterious effects of poverty on child development. Findings that these effects on the hippocampus are mediated by caregiving and stressful life events suggest that attempts to enhance early caregiving should be a focused public health target for prevention and early intervention. Findings substantiate the behavioral literature on the negative effects of poverty on child development and provide new data confirming that effects extend to brain development. Mechanisms for these effects on the hippocampus are suggested to inform intervention.
Vitamin D Insufficiency and Severe Asthma Exacerbations in Puerto Rican Children
Authors: John M. Brehm, Edna Acosta-Pérez, Lambertus Klei, Kathryn Roeder, Michael Barmada, Nadia Boutaoui, Erick Forno, Roxanne Kelly, Kathryn Paul, Jody Sylvia, Augusto A. Litonjua, Michael Cabana, María Alvarez, Angel Colón-Semidey, Glorisa Canino, Juan C. Celedón
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans.Objectives: To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors.Methods: A cross-sectional study was conducted of 560 children ages 6–14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates.Measurements and Main Results: Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5–4.9; P = 0.001) and atopy, and a lower FEV1/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2–21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1–4.1; P = 0.04) cases.Conclusions: Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.
Physics and Applications of Microfluidics in Biology
Authors: David J. Beebe, Glennys A. Mensing, Glenn M. Walker
Journal: Annual Review of Biomedical Engineering (2002)

Fluid flow at the microscale exhibits unique phenomena that can be leveraged to fabricate devices and components capable of performing functions useful for biological studies. The physics of importance to microfluidics are reviewed. Common methods of fabricating microfluidic devices and systems are described. Components, including valves, mixers, and pumps, capable of controlling fluid flow by utilizing the physics of the microscale are presented. Techniques for sensing flow characteristics are described and examples of devices and systems that perform bioanalysis are presented. The focus of this review is microscale phenomena and the use of the physics of the scale to create devices and systems that provide functionality useful to the life sciences.
The Basic Domain of HIV-Tat Transactivating Protein Is Essential for Its Targeting to Lipid Rafts and Regulating Fibroblast Growth Factor-2 Signaling in Podocytes Isolated from Children with HIV-1–Associated Nephropathy
Authors: Xuefang Xie, Anamaris M. Colberg-Poley, Jharna R. Das, Jinliang Li, Aiping Zhang, Pingtao Tang, Marina Jerebtsova, J. Silvio Gutkind, Patricio E. Ray
Journal: Journal of the American Society of Nephrology (2014)

Podocyte injury has a critical role in the pathogenesis of HIV-associated nephropathy (HIVAN). The HIV-1 transactivator of transcription (Tat), combined with fibroblast growth factor-2 (FGF-2), can induce the dedifferentiation and proliferation of cultured human podocytes. Cellular internalization of Tat requires interactions with heparan sulfate proteoglycans and cholesterol-enriched lipid rafts (LRs). However, the specific distribution of Tat in human podocytes and its ability to associate with LRs have not been documented. Here, we found that Tat is preferentially recruited to LRs in podocytes isolated from children with HIVAN. Furthermore, we identified arginines in the basic domain (RKKRRQRRR) of Tat as essential for (1) targeting Tat to LRs, (2) Tat-mediated increases in the expression of Rho-A and matrix metalloproteinase-9 in LRs, and (3) Tat-mediated enhancement of FGF-2 signaling in human podocytes and HIV-transgenic mouse kidneys and the exacerbation of renal lesions in these mice. Tat carrying alanine substitutions in the basic domain (AKKAAQAAA) remained localized in the cytosol and did not associate with LRs or enhance FGF-2 signaling in cultured podocytes. These results show the specific association of Tat with LRs in podocytes isolated from children with HIVAN, confirm Tat as a regulator of FGF-2 signaling in LRs, and identify the key domain of Tat responsible for promoting these effects and aggravating renal injury in HIV-transgenic mice. Moreover, these results provide a molecular framework for developing novel therapies to improve the clinical outcome of children with HIVAN.
Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure
Authors: Paul Palumbo, Jane C. Lindsey, Michael D. Hughes, Mark F. Cotton, Raziya Bobat, Tammy Meyers, Mutsawashe Bwakura-Dangarembizi, Benjamin H. Chi, Philippa Musoke, Portia Kamthunzi, Werner Schimana, Lynette Purdue, Susan H. Eshleman, Elaine J. Abrams, Linda Millar, Elizabeth Petzold, Lynne M. Mofenson, Patrick Jean-Philippe, Avy Violari
Journal: New England Journal of Medicine (2010)

Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown.