tbuckley/cabot-search huggingface dataset:
PERSPECTIVES ON NUTRITIONAL IRON DEFICIENCY
Authors: Leif Hallberg
Journal: Annual Review of Nutrition (2001)

Nutritional iron deficiency (ID) is caused by an intake of dietary iron insufficient to cover physiological iron requirements. Studies on iron absorption from whole diets have examined relationships between dietary iron bioavailability/absorption, iron losses, and amounts of stored iron. New insights have been obtained into regulation of iron absorption and expected rates of changes of iron stores or hemoglobin iron deficits when bioavailability or iron content of the diet has been modified and when losses of iron occur. Negative effects of ID are probably related to age, up to about 20 years, explaining some of earlier controversies. Difficulties in establishing the prevalence of mild ID are outlined. The degree of underestimation of the prevalence of mild ID when using multiple diagnostic criteria is discussed. It is suggested that current low-energy lifestyles are a common denominator for the current high prevalence not only of ID but also of obesity, diabetes, and osteoporosis. [Figure: see text]
Critical involvement of hydrogen peroxide in exercise-induced up-regulation of endothelial NO synthase
Authors: N LAUER, T SUVORAVA, U RUTHER, R JACOB, W MEYER, D HARRISON, G KOJDA
Journal: Cardiovascular Research (2004)

Recent studies from our groups have indicated that endothelial nitric oxide synthase (eNOS) expression is increased in cell culture by both shear stress and by hydrogen peroxide (H(2)O(2)). In vivo, exercise training, known to increase both endothelial shear stress and oxidative stress, also increases eNOS expression. It is unclear if H(2)O(2) contributes to an increase in eNOS expression in response to exercise training.To address this question, we generated mice overexpressing human catalase (hCat) driven by the murine Tie-2 promoter to specifically target this transgene to the endothelium (cat(++)).Vessels of cat(++) expressed significantly higher levels of catalase mRNA and catalase protein and activity but normal levels of eNOS. Exercise alone had no effect on catalase expression in C57BL/6. Wild-type littermates of cat(++) showed an increase in eNOS expression with 3 weeks of exercise (2.53+/-0.42-fold) comparable to C57BL/6 (2.93+/-0.45-fold). In striking contrast, 3 weeks of exercise had no effect on aortic (1.33+/-0.32-fold) and myocardial (1.1+/-0.2-fold) eNOS expression in catalase transgenic mice.These data suggest that endogenous H(2)O(2) plays a key role in the endothelial adaptation to exercise training by stimulating an up-regulation of eNOS.
Recombination events suggest potential sites for the Huntington's disease gene
Authors: Marcy E. MacDonald, Jonathan L. Haines, Michael Zimmer, Shirley V. Cheng, Sandra Youngman, W.Lance Whaley, Nancy Wexler, Maja Bucan, Bernice A. Allitto, Barbara Smith, Julie Leavitt, Annemarie Poustka, Peter Harper, Hans Lehrach, John J. Wasmuth, Anna-Marie Frischauf, James F. Gusella
Journal: Neuron (1989)
A female with cough, dyspnoea and chest pain
Authors: S. Suma, P. Polat, M. Görgüner
Journal: European Respiratory Journal (2001)

Case historyA 42-yr-old female presented with complaints of cough, dyspnoea and chest pain for 2 months.She was living in the eastern part of Turkey.As a child, she lived in the countryside, and her family earned their living by raising cattle.She has lived in the city for 10 yrs and did not have any animals in her house.There was neither sputum nor haemoptysis.She had lost weight, y3 kg in 4 months.Physical and biochemical examinations showed no apparent pathologies.A chest roentgenogram is shown in figure 1.A computed tomography (CT) section from the chest is shown in figure 2.Ultrasound examination of pleura-based lung lesions revealed anechoic cystic lesions.A CT-guided fine-needle aspiration was performed and 15 mL clear-white fluid was evacuated; the findings are shown in figure 3.
The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6
Authors: L LUCATS, L VINET, A BIZE, X MONNET, D MORIN, J SU, P ROUETBENZINEB, O CAZORLA, J MERCADIER, L HITTINGER
Journal: Cardiovascular Research (2006)

The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6. by Laurence Lucats, Laurent Vinet, Alain Bizé, Xavier Monnet, Didier Morin, Jin Bo Su, Patricia Rouet-Benzineb, Olivier Cazorla, Jean-Jacques Mercadier, Luc Hittinger, Alain Berdeaux, Bijan Ghaleh.Late preconditioning reduces contractile dysfunction during myocardial stunning. Mechanisms involving adaptation of calcium handling during excitation-contraction coupling to late preconditioning remain to be established. Thus, we investigated whether the late preconditioned myocardium is associated with contractile adaptation and changes in the cardiac ryanodine receptor (RyR2) and its regulatory protein FKBP12.6.Chronically instrumented conscious dogs (coronary occluder, ultrasonic crystals for sonomicrometry) underwent a 10-min coronary artery occlusion followed by reperfusion. They were studied 24 h later in the late preconditioned state (day 1).Maximal velocity of wall thickening at day 1 was increased as compared to corresponding baseline at day 0 (39+/-4 vs. 30+/-3 mm/s, p < 0.05) although systolic wall thickening was similar (2.8+/-0.2 vs. 2.9+/-0.2 mm), demonstrating a significant change in left ventricular inotropic state. Intracoronary infusion of ryanodine (0.5-6 microg) induced a dose-dependent decrease in wall thickening. In the late preconditioned state, this negative inotropic response was significantly reduced vs. control state, suggesting changes in sarcoplasmic reticulum (SR) Ca2+-release through RyR2. Immunoquantification of FKBP12.6 revealed a 2.8 fold ventricular increase after late preconditioning as compared to the control state. The amount of RyR2 and its phosphorylated state were similar and binding experiments did not reveal any alterations in B(max) or K(D) for RyR2. Calsequestrin, SERCA2a and phospholamban levels were not altered by late preconditioning.The late preconditioned myocardium is characterized by an adaptation of regional function associated with an increased expression of FKBP12.6. This demonstrates an adaptation of the SR Ca2+-release through RyR2 during late preconditioning.
Early Evolution of the Eukaryotic Ca2+ Signaling Machinery: Conservation of the CatSper Channel Complex
Authors: Xinjiang Cai, Xiangbing Wang, David E Clapham
Journal: Molecular Biology and Evolution (2014)

Calcium signaling is one of the most extensively employed signal transduction mechanisms in life. As life evolved into increasingly complex organisms, Ca(2+) acquired more extensive and varied functions. Here, we compare genes encoding proteins that govern Ca(2+) entry and exit across cells or organelles within organisms of early eukaryotic evolution into fungi, plants, and animals. Recent phylogenomics analyses reveal a complex Ca(2+) signaling machinery in the apusozoan protist Thecamonas trahens, a putative unicellular progenitor of Opisthokonta. We compare T. trahens Ca(2+) signaling to that in a marine bikont protist, Aurantiochytrium limacinum, and demonstrate the conservation of key Ca(2+) signaling molecules in the basally diverging alga Cyanophora paradoxa. Particularly, our findings reveal the conservation of the CatSper channel complex in Au. limacinum and C. paradoxa, suggesting that the CatSper complex likely originated from an ancestral Ca(2+) signaling machinery at the root of early eukaryotic evolution prior to the unikont/bikont split.
Differential Expression of Chemokines and Chemokine Receptors in Murine Islet Allografts
Authors: Bernd Schröppel, Nan Zhang, Peng Chen, Weiping Zang, Dongmei Chen, Kelly L. Hudkins, William A. Kuziel, Randall Sung, Jonathan S. Bromberg, Barbara Murphy
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Chemokines and their receptors play a pivotal role in the initiation and amplification of the immune response. Investigated was their differential expression after syngeneic and allogeneic islet transplantation. During the 7 d after transplantation, the chemokines MCP-1, MCP-2, RANTES, MIG, IP-10, I-TAC, and two CC chemokine receptors CCR2 and CCR5 were highly expressed in allografts when compared with isografts. Disrupting the CCR2 and CCR5 pathways individually resulted in prolongation of the survival time 16.1 ± 0.4 and 15.8 ± 0.9 d, respectively, of fully major histocompatibility complex–mismatched islet grafts compared with wild-type controls (11.2 ± 1.0 d). Blockade of both receptors had no synergistic effect. Rapamycin-treated wild-type recipients rejected their grafts at 17.4 ± 2.2 d, in contrast to rapamycin-treated CCR2−/− recipients at 38 ± 8.6 d (<i>P</i> = 0.025). The disruption of the CCR2 and CCR5 signaling, alone or in combination, moderately prolong islet allograft survival. However, the combination of low-dose immunosuppression and targeting of CCR2 greatly augmented islet graft survival.
Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes
Authors: Y. M van der Geld, T. Hellmark, D. Selga, P. Heeringa, M. G Huitema, P. C Limburg, C. G M Kallenberg
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Aim:</h3> In this study, we employed chimeric human/mouse Proteinase 3 (PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice. <h3>Method:</h3> Rats and mice were immunised with recombinant human PR3 (HPR3), recombinant murine PR3 (mPR3), single chimeric human/mouse PR3 (HHm, HmH, mHH, mmH, mHm, Hmm) or pools of chimeric proteins. Antibodies to mPR3 and HPR3 were measured by ELISA. Antibodies to rat PR3 were determined by indirect immunofluorescence (IIF) on rat white blood cells. Urinalysis was performed by dipstick analysis. Kidney and lung tissue was obtained for pathological examination. <h3>Results:</h3> In mice, immunisation with the chimeric human/mouse PR3 Hmm led to an autoantibody response to mPR3. Rats immunised with the chimeric human/mouse PR3 Hmm, HmH and mmH, or a pool of the chimeric human/mouse PR3 proteins, produced antibodies selectively binding to rat granulocytes as detected by IIF. No gross pathological abnormalities could be detected in kidney or lungs of mice or rats immunised with chimeric human/mouse PR3. <h3>Conclusion:</h3> Immunisation with chimeric human/mouse proteins induces autoantibodies to PR3 in rats and mice. Chimeric proteins can be instrumental in developing experimental models for autoimmune diseases.
Preoperative Hematocrit Levels and Postoperative Outcomes in Older Patients Undergoing Noncardiac Surgery
Authors: Wen-Chih Wu, Tracy L. Schifftner, William G. Henderson, Charles B. Eaton, Roy M. Poses, Georgette Uttley, Satish C. Sharma, Michael Vezeridis, Shukri F. Khuri, Peter D. Friedmann
Journal: JAMA (2007)

ContextElderly patients are at high risk of both abnormal hematocrit values and cardiovascular complications of noncardiac surgery. Despite nearly universal screening of patients for abnormal preoperative hematocrit levels, limited evidence demonstrates the adverse effects of preoperative anemia or polycythemia.ObjectiveTo evaluate the prevalence of preoperative anemia and polycythemia and their effects on 30-day postoperative outcomes in elderly veterans undergoing major noncardiac surgery.DesignRetrospective cohort study using the VA National Surgical Quality Improvement Program database. Based on preoperative hematocrit levels, we stratified patients into standard categories of anemia (hematocrit &lt;39.0%), normal hematocrit (39.0%-53.9%), and polycythemia (hematocrit ≥54%). We then estimated increases in 30-day postoperative cardiac event and mortality risks in relation to each hematocrit point deviation from the normal category.Setting and PatientsA total of 310 311 veterans aged 65 years or older who underwent major noncardiac surgery between 1997 and 2004 in 132 Veterans' Affairs medical centers across the United States.Main Outcome MeasuresThe primary outcome measure was 30-day postoperative mortality; a secondary outcome measure was composite 30-day postoperative mortality or cardiac events (cardiac arrest or Q-wave myocardial infarction).ResultsThirty-day mortality and cardiac event rates increased monotonically, with either positive or negative deviations from normal hematocrit levels. We found a 1.6% (95% confidence interval, 1.1%-2.2%) increase in 30-day postoperative mortality associated with every percentage-point increase or decrease in the hematocrit value from the normal range. Additional analyses suggest that the adjusted risk of 30-day postoperative mortality and cardiac morbidity begins to rise when hematocrit levels decrease to less than 39% or exceed 51%.ConclusionsEven mild degrees of preoperative anemia or polycythemia were associated with an increased risk of 30-day postoperative mortality and cardiac events in older, mostly male veterans undergoing major noncardiac surgery. Future studies should determine whether these findings are reproducible in other populations and if preoperative management of anemia or polycythemia decreases the risk of postoperative mortality.
TH1, TH2, and TH17 cells instruct monocytes to differentiate into specialized dendritic cell subsets
Authors: Michael N. Alonso, Michael T. Wong, Angela L. Zhang, Daniel Winer, Megan M. Suhoski, Lorna L. Tolentino, Juliana Gaitan, Matthew G. Davidson, Tiffany H. Kung, David M. Galel, Kari C. Nadeau, Jinah Kim, Paul J. Utz, Kalle Söderström, Edgar G. Engleman
Journal: Blood (2011)
Nitric Oxide Synthesis and Oxidative Stress in the Renal Cortex of Rats with Diabetes Mellitus
Authors: NAOHITO ISHII, KAUSHIK P. PATEL, PASCALE H. LANE, TRACI TAYLOR, KA BIAN, FERID MURAD, JENNIFER S. POLLOCK, PAMELA K. CARMINES
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Experiments were performed to test the hypothesis that diabetes mellitus disrupts the balance between synthesis and degradation of nitric oxide (NO) in the renal cortex. Diabetes was induced by injection of streptozotocin, and sufficient insulin was provided to maintain moderate hyperglycemia for the ensuing 2 wk. Despite an 80% increase in total NO synthase activity measured by L-citrulline assay, nicotinamide adenine dinucleotide phosphate-diaphorase staining was unaltered, and no changes in NO synthase isoform protein levels or their distribution were evident in renal cortex from diabetic rats. Superoxide anion production was accelerated twofold in renal cortical slices from diabetic rats, with an associated 50% increase in superoxide dismutase activity. Western blots prepared by use of a monoclonal antinitrotyrosine antibody revealed an approximately 70-kD protein in renal cortex from sham rats, the nitrotyrosine content of which was threefold greater in cortical samples from diabetic rats. These observations indicate that the early stage of diabetes mellitus provokes accelerated renal cortical superoxide anion production in a setting of normal or increased NO production. This situation can be expected to promote peroxynitrite formation, resulting in the tyrosine nitration of a single protein of unknown identity, as well as a decline in the bioavailability of NO. These events are consistent with the postulate that oxidative stress promotes NO degradation in the renal cortex during the early stage of diabetes mellitus.
Assessment of bronchodilatation after spontaneous recovery from a histamine challenge in asthmatic children.
Authors: P J Merkus, H M Rooda, E E van Essen-Zandvliet, E J Duiverman, P H Quanjer, K F Kerrebijn
Journal: Thorax (1992)

It would be convenient to be able to measure airway responsiveness to histamine and to bronchodilator drugs on the same day, but whether this can be done reliably is unknown.The effect of a prior histamine challenge on the bronchodilator response to salbutamol after spontaneous recovery of FEV1 to 95% of the prechallenge level was studied in two groups of asthmatic children. Fourteen children inhaled 400 micrograms salbutamol after spontaneous recovery from a histamine challenge, followed by a further 100 micrograms salbutamol 20 minutes later. In a second group of eight asthmatic children the study was repeated with 800 micrograms salbutamol, followed by a further 200 micrograms 20 minutes later.After histamine challenge FEV1 returned to baseline in 70 minutes or less on all occasions. The FEV1 20 minutes after 400 micrograms salbutamol was significantly lower after the histamine challenge than on the control day. After the further 100 micrograms salbutamol FEV1 values were similar after the histamine challenge and on the control day. FEV1 values after 800 micrograms salbutamol and the further 200 micrograms dose were not influenced by a prior histamine challenge.In children with stable asthma in whom FEV1 has returned to baseline after a histamine challenge the FEV1 achieved after 800 micrograms salbutamol is not affected by the histamine challenge. Histamine and bronchodilator responsiveness can thus be assessed reliably on the same day in patients with stable asthma. This has clear advantages for patient care.
Pyruvate dehydrogenase and the regulation of glucose oxidation in hypertrophied rat hearts
Authors: Carmen P Lydell, Andy Chan, Richard B Wambolt, Nandakumar Sambandam, Hannah Parsons, Gregory P Bondy, Brian Rodrigues, Kirill M Popov, Robert A Harris, Roger W Brownsey, Michael F Allard
Journal: Cardiovascular Research (2002)

Objective: Coupling of glucose oxidation to glycolysis is lower in hypertrophied than in non-hypertrophied hearts, contributing to the compromised mechanical performance of hypertrophied hearts. Here, we describe studies to test the hypothesis that low coupling of glucose oxidation to glycolysis in hypertrophied hearts is due to reduced activity and/or expression of the pyruvate dehydrogenase complex (PDC). Methods: We examined the effects of dichloroacetate (DCA), an inhibitor of PDC kinase, and of alterations in exogenous palmitate supply on coupling of glucose oxidation to glycolysis in isolated working hypertrophied and control hearts from aortic-constricted and sham-operated male Sprague–Dawley rats. It was anticipated that the addition of DCA or the absence of palmitate would promote PDC activation and consequently normalize coupling between glycolysis and glucose oxidation in hypertrophied hearts if our hypothesis was correct. Results: Addition of DCA or removal of palmitate improved coupling of glucose oxidation to glycolysis in control and hypertrophied hearts. However, coupling remained substantially lower in hypertrophied hearts. PDC activity in extracts of hypertrophied hearts was similar to or higher than in extracts of control hearts under all perfusion conditions. No differences were observed between hypertrophied and control hearts with respect to expression of PDC, PDC kinase, or PDC phosphatase. Conclusions: Low coupling of glucose oxidation to glycolysis in hypertrophied hearts is not due to a reduction in PDC activity or subunit expression indicating that other mechanism(s) are responsible.
Angiotensin II receptors on human platelets.
Authors: T J Moore, G H Williams
Journal: Circulation Research (1982)

The investigation of the interaction between angiotensin II and its receptors in human subjects has been hampered by the inaccessibility of human tissue containing angiotensin II receptors. In order to find a more accessible angiotensin II-binding tissue, we studied angiotensin II binding to platelets in normal human volunteers. Platelet preparations purified on Ficoll: Isopaque gradients were incubated with 125I-angiotensin II (30 pm), with and without unlabeled angiotensin at 22 degrees C, separating bound from free hormone by microcentrifugation. Binding was linearly related to the number of platelets incubated, and, at 8 X 10(5) cells/microliters, specific binding ranged from 0.8 to 10%. Scatchard analysis indicated a binding site with a Kd of 2.4 +/- 0.3 X 10(-10) m which agreed well with the Kd by displacement analysis (3.1 X 10(-10) m). The relative binding potencies for angiotensin II and analogues were: angiotensin II = des-Asp1 an angiotensin II greater than [Sar1, Ala8] angiotensin II greater than des-Asp1-[Ile8] angiotensin II greater than angiotensin I. The effect of high and low sodium (Na) intake (200 vs. 10 mEq/day) on platelet angiotensin II binding was studied in nine subjects. Compared to low Na, high Na intake produced an 80% increase in the angiotensin II-binding capacity (P less than 0.01) with no significant change in binding affinity. We conclude that human platelets possess angiotensin receptors whose binding characteristics and modulation by dietary sodium resemble the properties of the receptors on "classical" animal angiotensin target tissues. The platelet may provide an accessible source of angiotensin receptors for a detailed study of angiotensin-receptor interaction in human tissue.
Aprepitant, Granisetron and Dexamethasone Versus Palonosetron and Dexamethasone for Cisplatin-Induced Nausea and Vomiting in Patients with Upper Gastrointestinal Cancer: a Randomized Crossover Phase Ii Trial (Kdog 1002)
Authors: K. Ishido, K. Higuchi, M. Azuma, T. Sasaki, S. Tanabe, C. Katada, W. Koizumi
Journal: Annals of Oncology (2014)
Human keratinocytes are efficiently immortalized by a Rho kinase inhibitor
Authors: Sandra Chapman, Xuefeng Liu, Craig Meyers, Richard Schlegel, Alison A. McBride
Journal: Journal of Clinical Investigation (2010)

Primary human keratinocytes are useful for studying the pathogenesis of many different diseases of the cutaneous and mucosal epithelia. In addition, they can form organotypic tissue equivalents in culture that can be used as epidermal autografts for wound repair as well as for the delivery of gene therapy. However, primary keratinocytes have a finite lifespan in culture that limits their proliferative capacity and clinical use. Here, we report that treatment of primary keratinocytes (originating from 3 different anatomical sites) with Y-27632, a Rho kinase inhibitor, greatly increased their proliferative capacity and resulted in efficient immortalization without detectable cell crisis. More importantly, the immortalized cells displayed characteristics typical of primary keratinocytes; they had a normal karyotype and an intact DNA damage response and were able to differentiate into a stratified epithelium. This is the first example to our knowledge of a defined chemical compound mediating efficient cell immortalization, and this finding could have wide-ranging and profound investigational and medical applications.