tbuckley/cabot-search huggingface dataset:
The 'permeome' of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum.
Authors: Rowena E Martin, Roselani I Henry, Janice L Abbey, John D Clements, Kiaran Kirk
Journal: Genome biology (2005)

Abstract Background The uptake of nutrients, expulsion of metabolic wastes and maintenance of ion homeostasis by the intraerythrocytic malaria parasite is mediated by membrane transport proteins. Proteins of this type are also implicated in the phenomenon of antimalarial drug resistance. However, the initial annotation of the genome of the human malaria parasite Plasmodium falciparum identified only a limited number of transporters, and no channels. In this study we have used a combination of bioinformatic approaches to identify and attribute putative functions to transporters and channels encoded by the malaria parasite, as well as comparing expression patterns for a subset of these. Results A computer program that searches a genome database on the basis of the hydropathy plots of the corresponding proteins was used to identify more than 100 transport proteins encoded by P. falciparum . These include all the transporters previously annotated as such, as well as a similar number of candidate transport proteins that had escaped detection. Detailed sequence analysis enabled the assignment of putative substrate specificities and/or transport mechanisms to all those putative transport proteins previously without. The newly-identified transport proteins include candidate transporters for a range of organic and inorganic nutrients (including sugars, amino acids, nucleosides and vitamins), and several putative ion channels. The stage-dependent expression of RNAs for 34 candidate transport proteins of particular interest are compared. Conclusion The malaria parasite possesses substantially more membrane transport proteins than was originally thought, and the analyses presented here provide a range of novel insights into the physiology of this important human pathogen.
Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis
Authors: Yoon Seok Choi, Jeewon Lee, Hyun Woong Lee, Dong-Yeop Chang, Pil Soo Sung, Min Kyung Jung, Jun Yong Park, Ja Kyung Kim, Jung Il Lee, Hana Park, Jae Youn Cheong, Kyung-Suk Suh, Hyung Joon Kim, June Sung Lee, Kyung-Ah Kim, Eui-Cheol Shin
Journal: Gut (2014)

<h3>Objective</h3> Foxp3<sup>+</sup>CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells (Tregs) control immune responses, but their role in acute viral hepatitis remains elusive. Herein, we investigated alteration in the peripheral blood Treg population during acute hepatitis A (AHA) and its implication in the immune-mediated liver injury. <h3>Design</h3> The study included 71 patients with AHA, and peripheral blood mononuclear cells (PBMCs) were isolated. The suppressive activity of Treg population was determined by assessing anti-CD3/CD28-stimulated proliferation of Treg-depleted and reconstituted PBMCs. Treg cell frequency, phenotype and apoptosis in PBMCs were analysed by flow cytometry. <h3>Results</h3> The frequency of circulating Tregs was reduced during AHA. Moreover, the suppressive activity of the total Treg pool in the peripheral blood was attenuated during AHA. Treg frequency and suppressive activity of the Treg population inversely correlated with the serum alanine aminotransferase level. Fas was overexpressed on Tregs during AHA, suggesting their susceptibility to Fas-induced apoptosis. Indeed, increased apoptotic death was observed in Tregs of patients with AHA compared with healthy controls. In addition, agonistic anti-Fas treatment further increased apoptotic death of Tregs from patients with AHA. The decreased Treg frequency and Fas overexpression on Tregs were not observed in other acute liver diseases such as acute hepatitis B, acute hepatitis C and toxic/drug-induced hepatitis. <h3>Conclusions</h3> The size of the Treg pool was contracted during AHA, resulting from apoptosis of Tregs induced by a Fas-mediated mechanism. Decrease in Treg numbers led to reduced suppressive activity of the Treg pool and consequently resulted in severe liver injury during AHA.
N<scp>EW</scp> P<scp>ERSPECTIVES ON</scp> F<scp>OLATE</scp> C<scp>ATABOLISM</scp>
Authors: Jae Rin Suh, A Katherine Herbig, Patrick J Stover
Journal: Annual Review of Nutrition (2001)

▪ Abstract Folate catabolism has been assumed to result from the nonenzymatic oxidative degradation of labile folate cofactors. Increased rates of folate catabolism and simultaneous folate deficiency occur in several physiological states, including pregnancy, cancer, and when anticonvulsant drugs are used. These studies have introduced the possibility that folate catabolism may be a regulated cellular process that influences intracellular folate concentrations. Recent studies have demonstrated that the iron storage protein ferritin can catabolize folate in vitro and in vivo, and increased heavy-chain ferritin synthesis decreases intracellular folate concentrations independent of exogenous folate levels in cell culture models. Ferritin levels are elevated in most physiological states associated with increased folate catabolism. Therefore, folate catabolism is emerging as an important component in the regulation of intracellular folate concentrations and whole-body folate status.
Aldosterone in Metabolic Alkalosis*
Authors: Jerome P. Kassirer, Frederick M. Appleton, Joseph A. Chazan, William B. Schwartz
Journal: Journal of Clinical Investigation (1967)

Studies have been carried out in human volunteer subjects to evaluate the role of aldosterone in the development, maintenance, and correction of metabolic alkalosis induced by selective depletion of hydrochloric acid. During the first phase of our study the rate of aldosterone secretion was measured before the induction of alkalosis (while the subjects were on a low salt diet) and again after a steady state of metabolic alkalosis had been established. The data demonstrate a fall in aldosterone secretion from a value of approximately 500 mug/day to a value of approximately 200 mug/day. Thus, it appears that an increased rate of aldosterone secretion is not a prerequisite to the elevation of the renal bicarbonate threshold. During the second phase of our study, aldosterone was administered to the alkalotic subjects in doses of 1000 mug/day (or deoxycorticosterone acetate in doses of 40 mg/day) in order to determine the effects of a persistent steroid excess on the ability of sodium chloride to correct the acid-base disturbance. The data demonstrate that despite the administration of steroid, the ingestion of sodium chloride led to a reduction in plasma bicarbonate concentration from 39 to 29 mEq/liter, accompanied by a suppression of renal acid excretion. This reduction in plasma bicarbonate concentration occurred without a concomitant retention of potassium, a deficit of as much as 400-500 mEq of potassium persisting during repair of the acid-base disturbance. Our findings suggest that "saline-resistant" alkalosis, when it occurs in the absence of primary hyperadrenalism, cannot be attributed to aldosterone excess and/or potassium depletion of the magnitude seen in our study. We also suggest the need for a reappraisal of the way in which aldosterone excess contributes to the genesis and maintenance of alkalosis in primary aldosteronism.
The Relationship between Ambient Air Pollution and Heart Rate Variability Differs for Individuals with Heart and Pulmonary Disease
Authors: Amanda Wheeler, Antonella Zanobetti, Diane R. Gold, Joel Schwartz, Peter Stone, Helen H. Suh
Journal: Environmental Health Perspectives (2005)

Associations between concentrations of ambient fine particles [particulate matter < 2.5 microm aerodynamic diameter (PM2.5)] and heart rate variability (HRV) have differed by study population. We examined the effects of ambient pollution on HRV for 18 individuals with chronic obstructive pulmonary disease (COPD) and 12 individuals with recent myocardial infarction (MI) living in Atlanta, Georgia. HRV, baseline pulmonary function, and medication data were collected for each participant on 7 days in fall 1999 and/or spring 2000. Hourly ambient pollution concentrations were obtained from monitoring sites in Atlanta. The association between ambient pollution and HRV was examined using linear mixed-effect models. Ambient pollution had opposing effects on HRV in our COPD and MI participants, resulting in no significant effect of ambient pollution on HRV in the entire population for 1-, 4-, or 24-hr moving averages. For individuals with COPD, interquartile range (IQR) increases in 4-hr ambient PM2.5 (11.65 microg/m3)) and nitrogen dioxide (11.97 ppb) were associated with 8.3% [95% confidence interval (CI), 1.7-15.3%] and 7.7% (95% CI, 0.1-15.9%) increase in the SD of normal R-R intervals (SDNN), respectively. For individuals with MI, IQR increases in 4-hr PM2.5 (8.54 microg/m3) and NO2 (9.25 ppb) were associated with a nonsignificant 2.9% (95% CI, -7.8 to 2.3) and significant 12.1 (95% CI, -19.5 to -4.0) decrease in SDNN. Beta-blocker and bronchodilator intake and baseline forced expiratory volume in 1 sec modified the PM-SDNN association significantly, with effects consistent with those by disease group. Results indicate heterogeneity in the autonomic response to air pollution due to differences in baseline health, with significant associations for ambient NO2 suggesting an important role for traffic-related pollution.
Essential thrombocythemia in a child: Platelet ultrastructure and function
Authors: Marion I. Barnhart, Tae H. Kim, Bruce L. Evatt, Abdelsalam H. Ragab, Victor K. Lui, Jay Herman, Jeanne M. Lusher
Journal: American Journal of Hematology (1980)

Abstract A nine‐year‐old black girl with essential thrombocythemia developed hemoptysis. Only two other cases in the English literature have been described. Ultrastructure and functional characteristics of this patient's platelets were studied. Twenty‐six percent of the patient's platelets were very large (megathrombocytes). Spontaneous aggregates from the patient's platelets were not compact, and the pseudopods did not interdigitate. Both qualitative and quantitative defects in platelet organelles were detected. The microtubular system was faulty in organization. Furthermore, the number of granules (especially alpha granules) was reduced. Platelet aggregation studies demonstrated subnormal aggregation in response to ADP, epinephrine, and collagen, but aggregation with ristocetin was normal. It is postulated that a platelet membrane abnormality may be the cause of their defective platelet aggregation.
Protection from Pulmonary Fibrosis in Leukotriene-Deficient Mice
Authors: MARC PETERS-GOLDEN, MARC BAILIE, TERESA MARSHALL, CAROL WILKE, SEM H. PHAN, GALEN B. TOEWS, BETHANY B. MOORE
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Although overproduction of proinflammatory 5-lipoxygenase (5-LO)-derived leukotrienes (LTs) has been demonstrated in the lungs of patients with pulmonary fibrosis, their causal involvement in this condition has not been established. Bleomycin-induced pulmonary fibrosis was studied in mice rendered LT deficient by knockout of the 5-LO gene (KO) and in wild-type (WT) control mice. Following administration of bleomycin, lung lavage fluid of WT mice demonstrated an ∼ 5-fold increase in levels of cysteinyl-LTs over baseline levels at Day 1, with persistent elevation up to Day 21. As compared with WT mice, 5-LO KO mice demonstrated reduced amounts of histologically evident collagen as well as an ∼ 60% reduction in lung hydroxyproline levels postbleomycin. Unlike WT mice, KO mice showed no increases in the numbers of lung inflammatory cells postbleomycin. Furthermore, in situ expression and stimulated production by mixed lung leukocytes of the antifibrotic cytokine interferon- γ were significantly greater in cells from the 5-LO KO mice. Finally, lavage levels of the antiinflammatory and antifibrotic molecule, prostaglandin E2, were significantly greater in the KO animals. These results provide strong evidence that LTs may participate in the pathogenesis of pulmonary fibrosis, and they may do so by direct effects as well as indirect effects occurring via their modulation of the synthesis of other inflammatory mediators.
Naive T Cells Transiently Acquire a Memory-like Phenotype during Homeostasis-Driven Proliferation
Authors: Ananda W. Goldrath, Lisa Y. Bogatzki, Michael J. Bevan
Journal: The Journal of Experimental Medicine (2000)

In a depleted lymphoid compartment, naive T cells begin a slow proliferation that is independent of cognate antigen yet requires recognition of major histocompatibility complex–bound self-peptides. We have followed the phenotypic and functional changes that occur when naive CD8+ T cells undergo this type of expansion in a lymphopenic environment. Naive T cells undergoing homeostasis-driven proliferation convert to a phenotypic and functional state similar to that of memory T cells, yet distinct from antigen-activated effector T cells. Naive T cells dividing in a lymphopenic host upregulate CD44, CD122 (interleukin 2 receptor β) and Ly6C expression, acquire the ability to rapidly secrete interferon γ, and become cytotoxic effectors when stimulated with cognate antigen. The conversion of naive T cells to cells masquerading as memory cells in response to a homeostatic signal does not represent an irreversible differentiation. Once the cellularity of the lymphoid compartment is restored and the T cells cease their division, they regain the functional and phenotypic characteristics of naive T cells. Thus, homeostasis-driven proliferation provides a thymus-independent mechanism for restoration of the naive compartment after a loss of T cells.
Occupational vitiligo: clinical and epidemiological aspects
Authors: C.J. STEVENSON
Journal: British Journal of Dermatology (1981)

Journal Article Occupational vitiligo: clinical and epidemiological aspects Get access C.J. STEVENSON C.J. STEVENSON Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 105, Issue s21, 1 September 1981, Pages 51–56, https://doi.org/10.1111/j.1365-2133.1981.tb01310.x Published: 01 September 1981
Cixutumumab for patients with recurrent or refractory advanced thymic epithelial tumours: a multicentre, open-label, phase 2 trial
Authors: Arun Rajan, Corey A Carter, Arlene Berman, Liang Cao, Ronan J Kelly, Anish Thomas, Sean Khozin, Ariel Lopez Chavez, Isabella Bergagnini, Barbara Scepura, Eva Szabo, Min-Jung Lee, Jane B Trepel, Sarah K Browne, Lindsey B Rosen, Yunkai Yu, Seth M Steinberg, Helen X Chen, Gregory J Riely, Giuseppe Giaccone
Journal: The Lancet Oncology (2014)
MECHANICAL PROPERTIES OF LUNG IN NORMAL MEN OVER 60 YEARS OLD*
Authors: J. E. Cohn, H. D. Donoso
Journal: Journal of Clinical Investigation (1963)

There are conflicting reports concerning the ef- fects of aging on mechanical properties of the human respiratory system (1-4).The present study was undertaken to collect additional information pertaining to the relationships between normal aging and lung mechanics.Besides the mechanics measurements, data are reported for lung volumes, intrapulmonary gas mixing, and ventilatory capacity. METHODSNineteen subjects over 60 years old were selected who a) were free from complaints referable to cardiac, pul- monary, or neuromuscular systems; b) had normal physical examinations; and c) demonstrated normal chest roentgenograms and electrocardiograms.These men constitute group I subjects.Similar criteria were applied in selection of 13 men under 40 who comprised group II.Eight older men and six of the younger were cigarette smokers.Physical characteristics of the two groups are shown in Table I.Spirograms were recorded with a 13.5 L Collins 1 spirometer from which all valves had been removed.A closed-circuit, constant-volume, helium (He) -dilution method was used to measure the functional residual ca- pacity (FRC) in seated subjects.Lung compartments and their ratios were calculated.Intrapulmonary distri- bution of inspired gas was evaluated by the N2 single- breath test (5).The dynamic lung compliance (Cdyn) was determined by the methods of Mead and Whittenberger (6).Mouth-esophageal pressure gradients were detected by a differential pressure transducer.2The signal was am- plified and displayed on the horizontal axis of a cathode- ray oscilloscope a (CRO).Flow rates were measured
Complications following closure of atrial septal defects of the inferior vena caval type
Authors: J. K. Ross, D. C. Johnson
Journal: Thorax (1972)

An atrial septal defect of the inferior vena caval type presents complicated anatomy to the surgeon at operation. Four cases are presented illustrating two complications of repair. Incomplete closure or reopening due to disruption of the suture line may be prevented by accurate identification of the anatomy and a patch closure. Two cases of inadvertent diversion of the inferior vena cava into the left atrium are presented and the methods of diagnosis and techniques of repair are discussed. Mitral regurgitation due to ballooning of the posterior cusp in systole was an associated lesion in two cases of atrial septal defect of this type.
Iron regulates T-lymphocyte sensitivity to the IFN-γ/STAT1 signaling pathway in vitro and in vivo
Authors: Gabriella Regis, Marita Bosticardo, Laura Conti, Stefania De Angelis, Daniela Boselli, Barbara Tomaino, Paola Bernabei, Mirella Giovarelli, Francesco Novelli
Journal: Blood (2004)
A Novel Algorithm for Simplification of Complex Gene Classifiers in Cancer
Authors: Raphael A. Wilson, Ling Teng, Karen M. Bachmeyer, Mei Lin Z. Bissonnette, Aliya N. Husain, David M. Parham, Timothy J. Triche, Michele R. Wing, Julie M. Gastier-Foster, Frederic G. Barr, Douglas S. Hawkins, James R. Anderson, Stephen X. Skapek, Samuel L. Volchenboum
Journal: Cancer Research (2013)

Abstract The clinical application of complex molecular classifiers as diagnostic or prognostic tools has been limited by the time and cost needed to apply them to patients. Using an existing 50-gene expression signature known to separate two molecular subtypes of the pediatric cancer rhabdomyosarcoma, we show that an exhaustive iterative search algorithm can distill this complex classifier down to two or three features with equal discrimination. We validated the two-gene signatures using three separate and distinct datasets, including one that uses degraded RNA extracted from formalin-fixed, paraffin-embedded material. Finally, to show the generalizability of our algorithm, we applied it to a lung cancer dataset to find minimal gene signatures that can distinguish survival. Our approach can easily be generalized and coupled to existing technical platforms to facilitate the discovery of simplified signatures that are ready for routine clinical use. Cancer Res; 73(18); 5625–32. ©2013 AACR.
Cigarette Smoke Exposure Reprograms the Hypothalamic Neuropeptide Y Axis to Promote Weight Loss
Authors: Hui Chen, Michelle J. Hansen, Jessica E. Jones, Ross Vlahos, Steve Bozinovski, Gary P. Anderson, Margaret J. Morris
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Despite irrefutable epidemiologic evidence, cigarette smoking remains the major preventable cause of lung disease morbidity worldwide. The appetite-suppressing effect of tobacco is a major behavioral determinant of smoking, but the underlying molecular and neuronal mechanisms are not understood. Neuropeptide Y (NPY) is an orexigenic neuropeptide, whose activity in the hypothalamic paraventricular nucleus governs appetite.Objectives: To compare the effects of smoke exposure and equivalent food restriction on body weight, organ mass, cytokines, and brain NPY in Balb/c mice.Methods: A pair-feeding study design compared smoke exposure (4 wk; 1 cigarette, 3×/d, 5 d/wk) to equivalent food restriction (pair-fed) and sham-exposed control mice.Results: Smoke exposure rapidly induced mild anorexia. After 4 wk, smoke-exposed and pair-fed groups were lighter than control mice (22.0 ± 0.2, 23.2 ± 0.5, 24.9 ± 0.4 g, respectively; p < 0.05). Brown and white fat masses were only reduced by smoke exposure, relative to control mice. NPY concentration in the paraventricular nucleus was significantly and paradoxically reduced by smoke exposure, despite lower plasma leptin concentrations; this was not observed in the pair-fed group experiencing 19% food restriction. Adipose mRNA expression of uncoupling proteins, inflammatory cytokines interleukin 6 and tumor necrosis factor α, and adipose triglyceride lipase was decreased by smoke exposure, and even lower in pair-fed mice.Conclusions: In contrast to food restriction, smoke exposure caused a reduction in hypothalamic NPY and fat mass, and regulated adipose cytokines. These findings may contribute to understanding weight loss in smoking-related lung disease and in the design of more effective smoking cessation strategies.
Pdx1 restores β cell function in Irs2 knockout mice
Authors: Jake A. Kushner, Jing Ye, Markus Schubert, Deborah J. Burks, Matthew A. Dow, Carrie L. Flint, Sanjoy Dutta, Christopher V.E. Wright, Marc R. Montminy, Morris F. White
Journal: Journal of Clinical Investigation (2002)

The homeodomain transcription factor Pdx1 is required for pancreas development, including the differentiation and function of β cells. Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic β cell growth and function. To investigate whether β cell failure in Irs2–/– mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2–/– mice. Before the onset of diabetes, Pdx1 was reduced in islets from Irs2–/– mice, whereas it was expressed normally in islets from wild-type or Irs1–/– mice, which do not develop diabetes. Whereas male Irs2–/–Pdx1+/+ mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2–/– mice. By contrast, transgenic expression of Pdx1 restored β cell mass and function in Irs2–/– mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY.