tbuckley/cabot-search huggingface dataset:
Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient
Authors: Xiaowen Liu, Tao Yang, Koya Suzuki, Sachiko Tsukita, Masaru Ishii, Shuping Zhou, Gang Wang, Luyang Cao, Feng Qian, Shalina Taylor, Myung-Jin Oh, Irena Levitan, Richard D. Ye, Graeme K. Carnegie, Yong Zhao, Asrar B. Malik, Jingsong Xu
Journal: The Journal of Experimental Medicine (2015)

Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in the correct direction, and engulfing the bacteria. How neutrophils establish and precisely orient this polarity toward pathogens remains unclear. Here we report that in resting neutrophils, the ERM (ezrin, radixin, and moesin) protein moesin in its active form (phosphorylated and membrane bound) prevented cell polarization by inhibiting the small GTPases Rac, Rho, and Cdc42. Attractant-induced activation of myosin phosphatase deactivated moesin at the prospective leading edge to break symmetry and establish polarity. Subsequent translocation of moesin to the trailing edge confined the formation of a prominent pseudopod directed toward pathogens and prevented secondary pseudopod formation in other directions. Therefore, both moesin-mediated inhibition and its localized deactivation by myosin phosphatase are essential for neutrophil polarization and effective neutrophil tracking of pathogens.
Evaluate the potential of IP-10 as biomarker for the MDR-TB treatment outcome
Authors: Yi-Wen Huang, Hsin-Chieh Tsai, Chia-Ming Chen, Ya-Yen Yu, Gwan-Han Shen, Wen-Ta Yang
Journal: European Respiratory Journal (2013)

Introduction 

Interferon gamma inducible protein-10 (IP-10) has been suggested as an alternative marker to diagnose TB recently. A higher level of IP-10 was observed in antigen or mitogen stimulated TB blood samples. Increased IP-10 activity in response to TB specific antigens in TB patients has also been observed to decrease after successful therapy. This study aims to evaluate the potential of IP-10 values to be used as biomarkers to assess MDR-TB treatment.

Methods 

This study recruited a total of 67 patients including 20 tuberculosis (TB), 17 multi-drug resistant tuberculosis (MDR-TB) and 30 healthy cases (HC). Blood samples were taken from each subject to measure the IP-10 values at the beginning of the experiment and at 2 weeks, 2 months and 6 months after treatment. The values were compared with the sputum results to evaluate changes in antigen values during treatment.

Results 

Higher levels of IP-10 and TB antigen were observed in the TB (458.7±301.9pg/ml, 2.1pg/ml) and the MDR-TB groups (513.7±279.8pg/ml, 1.6pg/ml) than the HC case (131.9±102.8pg/ml, 0.4pg/ml). However, no regular patterns were found for the changes in TB antigen or IP-10 values in the two treatment groups. Nevertheless, after 6 months of anti-TB treatment, significant decrease in IP10 values was noted in both the TB (271.7±254.5pg/ml) and MDR-TB (303.6±273.7pg/m) groups. In addition, the IP-10 levels and the TB antigen values were lower when sputum smear and culture were negative as compared to when both were positive.

Conclusion 

A single IP-10 value cannot be used as a biomarker to confirm sputum conversion, however, the IP-10 value can assist to detect a higher risk tuberculosis group and be used to assess treatment outcome.
The U.K. skin cancer ‘two-week rule’ proforma: assessment of potential modifications to improve referral accuracy
Authors: N.H. Cox, V. Madan, T. Sanders
Journal: British Journal of Dermatology (2008)

In England and Wales, patients with suspected skin cancer are referred to specialists within 2 weeks ('two-week rule', TWR) by tick-box proforma.To evaluate proforma details that might be amended to improve sensitivity and specificity.Five hundred and six TWR referrals were evaluated. Potential proforma changes were criteria for melanoma, and guidance that most squamous cell carcinomas (SCCs) measure >or= 1 cm. We compared melanomas vs. benign pigmented lesions using seven-point, and amended (10-point), checklist scores. We examined sizes of 82 SCCs and investigated influence of size on TWR referral.Of 506 TWR referrals, 381 (75%) were suspected melanoma [30 (7.8%) correct], and 125 (25%) were suspected SCC [22 (17.6%) correct]. Fifty per cent of melanomas were referred by TWR, but only 8% of SCC. No combination of seven-point checklist criteria had discriminatory value for melanoma; total scores (seven- or 10-point) were not significantly different between melanomas and nonmelanomas. No total score, using either system, had acceptable sensitivity and specificity. Measured size of SCCs varied from 4 to 30 mm; 88% were >or= 1 cm. Reducing the 'cut-off' to 7 mm identified only another 3.5%. Even at 2.5-3 cm, only 50% of SCCs were referred by TWR.The seven-point checklist for melanoma, when used in TWR format, does not have discriminatory value for melanoma. Altering the suggested cut-off size for SCC is unlikely to alter referrals. Education may be a more important factor in refining use of the TWR.
Vascular Anomalies in Alagille Syndrome
Authors: Binita M. Kamath, Nancy B. Spinner, Karan M. Emerick, Albert E. Chudley, Carol Booth, David A. Piccoli, Ian D. Krantz
Journal: Circulation (2004)

Background— Alagille syndrome (AGS) is a dominantly inherited multisystem disorder involving the liver, heart, eyes, face, and skeleton, caused by mutations in Jagged1 . Intracranial bleeding is a recognized complication and cause of mortality in AGS. There are multiple case reports of intracranial vessel abnormalities and other vascular anomalies in AGS. The objective of this study was to characterize the nature and spectrum of vascular anomalies in AGS. Methods and Results— Retrospective chart review of 268 individuals with AGS was performed. Twenty-five patients (9%) had noncardiac vascular anomalies or events. Sixteen patients had documented structural vascular abnormalities. Two had basilar artery aneurysms, 7 had internal carotid artery anomalies, and another had a middle cerebral artery aneurysm. Moyamoya disease was described in 1 patient. Three of the 16 patients had aortic aneurysms, and 2 had aortic coarctations. One of the patients with a basilar artery aneurysm also had coarctation of the aorta. One of the individuals with an internal carotid artery anomaly also had renal artery stenosis. Nine more patients had intracranial events without documented vessel abnormalities. Vascular accidents accounted for 34% of the mortality in this cohort. Conclusions— The vascular anomalies described in our cohort of AGS individuals identify an underrecognized and potentially devastating complication of this disorder. It is a major cause of morbidity and mortality in this population, accounting for 34% of the mortality. We have also reviewed the body of evidence supporting a role for Jagged1 and the Notch signaling pathway in vascular development.
Serum Follicular-Stimulating Hormone and Luteinizing Hormone as Measured by Radioimmunoassay Correlated with Sexual Development in Hypopituitary Subjects
Authors: Robert Penny, Thomas P. Foley, Robert M. Blizzard
Journal: Journal of Clinical Investigation (1972)

Serum follicular-stimulating hormone (FSH) and luteinizing hormone (LH) as determined by radioimmunoassay, were correlated with sexual development in 29 patients with hypopituitarism (ages 14.2-29.9 yr).
Transcription factor T-bet regulates inflammatory arthritis through its function in dendritic cells
Authors: J. Wang
Journal: Journal of Clinical Investigation (2006)

The transcription factor T-bet (Tbx21) plays a major role in adaptive immunity and is required for optimal IFN-γ production by DCs. Here we demonstrate an essential function for T-bet in DCs in controlling inflammatory arthritis. We show that collagen antibody–induced arthritis (CAIA), a model of human RA, is a bipartite disease characterized by an early innate immune system component intact in RAG2–/– mice and a later adaptive immune system phase. Mice lacking T-bet had markedly reduced joint inflammation at both early and late time points and RAG2–/–T-bet–/– double-deficient mice were essentially resistant to disease. Remarkably, adoptive transfer of T-bet–expressing DCs reconstituted inflammation in a T-bet deficient and T-bet/RAG2–deficient milieu. T-bet regulates the production of proinflammatory cytokine IL-1α and chemokines macrophage inflammatory protein-1α (MIP-1α) and thymus- and activation-related chemokine (TARC) by DCs. Further, T-bet expression in DCs is required for T helper cell activation. We conclude that T-bet plays a vital function in DCs that links innate and adaptive immunity to regulate inflammatory responses. T-bet provides an attractive new target for the development of novel therapeutics for inflammatory arthritis.
Multidrug resistance-associated proteins are crucial for the viability of activated rat hepatic stellate cells
Authors: Rebekka A. Hannivoort, Sandra Dunning, Sara Vander Borght, Ben Schroyen, Jannes Woudenberg, Fiona Oakley, Manon Buist-Homan, Fiona A. J. van den Heuvel, Mariska Geuken, Albert Geerts, Tania Roskams, Klaas Nico Faber, Han Moshage
Journal: Hepatology (2008)

Abstract Hepatic stellate cells (HSCs) survive and proliferate in the chronically injured liver. ATP-binding cassette (ABC) transporters play a crucial role in cell viability by transporting toxic metabolites or xenobiotics out of the cell. ABC transporter expression in HSCs and its relevance to cell viability and/or activation have not been reported so far. The aim of this study was to investigate the expression, regulation, and function of multidrug resistance–associated protein (Mrp)-type and multidrug resistance protein (Mdr)–type ABC transporters in activated rat HSCs. Rat HSCs were exposed to cytokines or oxidative stress. ABC transporter expression was determined by quantitative polymerase chain reaction and immunohistochemistry. HSCs were exposed to the Mdr inhibitors verapamil and PSC-833 and the Mrp inhibitor MK571. Mdr and Mrp transporter function was evaluated with flow cytometry. Apoptosis was determined by activated caspase-3 and acridine orange staining, and necrosis was determined by Sytox green nuclear staining. An in vivo model of carbon tetrachloride (CCl4)–induced liver fibrosis was used. With respect to hepatocytes, activated HSCs expressed high levels of Mrp1 and comparable levels of Mrp3, Mrp4, Mdr1a, and Mdr1b but not the hepatocyte-specific transporters bile salt export pump, Mrp2, and Mrp6. Mrp1 protein staining correlated with desmin staining in livers from CCl4-treated rats. Mrp1 expression increased upon activation of HSCs. Cytokines induced Mdr1b expression only. Oxidative stress was not a major regulator of Mdr and Mrp transporter expression. Activated HSCs became necrotic when exposed to the Mrp inhibitors. Conclusion: Activated HSCs contain relatively high levels of Mrp1. Mrp-type transporters are required for the viability of activated HSCs. Mrp-dependent export of endogenous metabolites is important for the survival of activated HSCs in chronic liver diseases. (HEPATOLOGY 2008.)
Trends, Major Medical Complications, and Charges Associated With Surgery for Lumbar Spinal Stenosis in Older Adults
Authors: Richard A. Deyo
Journal: JAMA (2010)

geons have wide discretion.For pain-related surgery, consensus on indications for specific procedures (eg, decompression alone or decompression plus fusion) is generally lacking 1-3 despite randomized trials for some condition and procedure combinations. 4-10Furthermore, individual surgeon preferences may outweigh patient and disease characteristics in choosing procedures. 3[10]12 Risks of spine surgery are particularly important in older adults, for whom stenosis is the most common surgical indication.Symptomatic lumbar stenosis results from progressive degenerative changes in intervertebral joints and ligamentous structures, leading to spinal canal and neural foraminal narrowing.Diagnosis and treatment require complex judgments integrating data from imaging, clini-
The absorption of tritium-labelled pyridoxine HCl in control subjects and in patients with intestinal malabsorption
Authors: M. C. Brain, C. C. Booth
Journal: Gut (1964)

EDITORIAL SYNOPSIS It has been suggested that there may be subclinical deficiency of pyridoxine in patients with tropical and non-tropical sprue.This paper provides evidence of some failure of absorption of pyridoxine in idiopathic steatorrhoea.'Postal address: Du Cane Road, London W.12. METHOD 3H-LABELLED PYRIDOXINE This was prepared by the Radiochemical Centre, Amersham, from commercial pyridoxine hydrochloride (British Drug Houses).The resulting material had a specific activity of 1-6 mc. per
TRIM79α, an Interferon-Stimulated Gene Product, Restricts Tick-Borne Encephalitis Virus Replication by Degrading the Viral RNA Polymerase
Authors: R. Travis Taylor, Kirk J. Lubick, Shelly J. Robertson, James P. Broughton, Marshall E. Bloom, Wade A. Bresnahan, Sonja M. Best
Journal: Cell Host & Microbe (2011)
L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer
Authors: Verena Tischler, Marco Pfeifer, Silke Hausladen, Uwe Schirmer, Anne-Katrine Bonde, Glen Kristiansen, Martin L Sos, Walter Weder, Holger Moch, Peter Altevogt, Alex Soltermann
Journal: Molecular Cancer (2011)

The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition. L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown. A subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.
The Influence of Polyvinyl Chloride (P.V.C.) Tubing on the Isolated Perfused Rat's Heart
Authors: F. L. MEYLER, A. F. WILLEBRANDS, D. DURRER
Journal: Circulation Research (1960)

Perfusion of the isolated rat's heart through certain types of polyvinyl chloride tubing results in a deterioration of cardiac performance. Since plastics are commonly used in heart-lung machines and transfusion-sets, this observation may be of some importance.
Developmental Neurobiology and the Natural History of Nerve Growth Factor
Authors: Rita Levi-Montalcini
Journal: Annual Review of Neuroscience (1982)

I was invited to write about the discovery of Nerve Growth Factor and its relationship to developmental neurobiology. Rather than detail the life of NGF over the past 30 years, I wish to concentrate on what was the most attractive and also the most unusual feature in the investigation of NGF: that each finding has signaled a new turning point and opened up a new perspective. The story of NGF is therefore more like a detective story than a scientific enterprise, since science usually unfolds according to well-defined rules, along the route paved by previous findings. In retrospect, the previous experience with NGP holds out the promise that as many turning points still await us on the road ahead as we experienced on the road we have traveled so far. To me this is an encouraging rather than a depressing thought; the abrupt end of a scientific pursuit is more often synonymous with an intellectual dead end than with a goal successfully achieved. By way of introduction, I shall recount the early beginnings of this research, which are well known to old-timers but probably not to biochemically trained newcomers who were lured to take part in this game by the molecule itself and who are only vaguely acquainted with its natural history and with its problems.
HIV-1 gp120 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent, pertussis toxin–insensitive chemokine receptor signaling
Authors: Manuela Del Corno, Qing-Hua Liu, Dominique Schols, Erik de Clercq, Sandra Gessani, Bruce D. Freedman, Ronald G. Collman
Journal: Blood (2001)
Interleukin 18 preserves a perforin-dependent graft-versus-leukemia effect after allogeneic bone marrow transplantation
Authors: Pavan Reddy, Takanori Teshima, Gerhard Hildebrandt, Ulrich Duffner, Yoshinobu Maeda, Kenneth R. Cooke, James L. M. Ferrara
Journal: Blood (2002)
Pulmonary permeability in primary ciliary dyskinesia
Authors: S Groth, M Pedersen
Journal: European Respiratory Journal (1989)

Pulmonary clearance (Pcl) of aerosolized 99mTc-DTPA was studied in fourteen patients with primary ciliary dyskinesia (PCD), (median age 23.5 yrs, range 12-44 yrs) and nine normal individuals (median age 23 yrs, range 18-27 yrs). All had never smoked. Regional Pcl was studied for arbitrarily defined central and peripheral regions of the lung using a gamma camera method, whilst total Pcl was studied by a plasma sample method. The patients with PCD had significantly reduced total Pcl compared to the normal individuals (p less than 0.05) and also significantly lower total lung capacity (TLC), vital capacity (VC), forced expiratory volume in one second (FEV1), and FEV1/VC values (p less than 0.05). There was no correlation between Pcl and FEV1/VC. It is concluded that the reduced Pcl in the PCD patients may be associated with their small lung volumes. In addition, reduced bronchial clearance of surfactant in PCD may be associated with an increased alveolar lining fluid volume and/or an impaired movement of 99mTc-DTPA along the alveolar septa to the bronchoalveolar junction, where the epithelium may be more specialized for absorption.
Acid-base regulation of hepatic glutamine metabolism and ureagenesis
Authors: I Nissim, C Cattano, Z Lin, I Nissim
Journal: Journal of the American Society of Nephrology (1993)

The metabolism of (5-15N)glutamine and (2-15N) glutamine has been studied by isolated hepatocytes obtained from either control, chronically acidotic, or alkalotic rats. The main goal was to elucidate the mechanism(s) by which altered acid-base state affects hepatic ureagenesis from glutamine. Isolated hepatocytes were incubated in Krebs buffer (pH 7.4) supplemented with 0.1 mM ornithine plus either 1 mM (5-15N)glutamine or (2-15N)glutamine. To elucidate the role of glutamine cycling in net ammonia metabolism, a separate series of experiments were performed with 1 mM unlabeled glutamine plus 1 mM (15N)H4Cl. Net glutamine utilization was significantly lower in hepatocytes obtained from chronically acidotic rats compared with control or alkalotic rats. The sum of the rates of 15NH3 and (15N)urea production from (5-15N)glutamine was decreased in acidosis compared with alkalosis. After incubations of 50 min, approximately 75, 65, or 90% of the N in carbamoyl-phosphate was derived from the 5-N of glutamine in control, acidosis, or alkalosis respectively. In experiments with (2-15N)glutamine, the production of singly and doubly labeled (15N)urea as well as (15N)aspartate and (15N)H3 was significantly smaller in acidosis compared with alkalosis. Furthermore, a correlation was observed between production rates of (15N)aspartate and (15N)urea, suggesting that alterations in urea production may depend on aspartate formed from glutamine. However, the production of (15N)alanine was higher in acidosis compared with alkalosis with apparent correlation between the production of (15N)alanine and 2-oxoglutaramate, a product of the glutamine aminotransferase pathway. In addition, the rate of glutamine recycling was significantly higher in acidosis compared with control or alkalosis, indicating that both flux through glutamine aminotransferase and flux through glutamine synthetase were elevated in acidosis compared with alkalosis. These data suggest that decreased formation of aspartate from glutamine may limit ureagenesis in chronic metabolic acidosis. The formation of aspartate may depend on the availability of oxaloacetate rather than diminished flux through transaminase reaction. The enhancement of alanine production and glutamine synthesis may provide an alternate route of N disposal in cases of diminished urea formation.
INTUSSUSCEPTION SUPERVENING ON CONGENITAL STENOSIS OF THE ILEUM
Authors: W. T. Warwick
Journal: BMJ (1923)

A tDICL 0UIAJ two or tlhree times the calcification of the skeleton was either not increased at all or only slightly.3. The ingestion of even very large quantities of calcium did not cure the rachitic calcium impoverishment of the skeleton of rats on a diet deficient in the fat-solable factor.4. When the exllaustion of the fat-soluble factor iu tlle body of rats is not complete, an excess of calcium in diets deficient in fat-soluble factor may in some cases slightly increase the amount of calcium in the skeleton, though never sufficient to make the calcification norimal.5. On the basis of the data of the cllemical and histological examination, the skeletal affections in rats on -A diet must be classed in the group of rachitic affections, which develop even with an excess of calcium in the diet.The grant of thle Medical Researclh Council and thle llos- pitality of the laboratories of-the Listar Institute liavo enabled me to carry out this work, and to them my tllanks are due.I wish also to express my sincere gratitude to Professor C. J. Martin for hlis continuous support in this investigation, and to Miss M. Carr foi her assistance ii chemical analyses.
Artifactual Serum Alkaline Phosphatase From Placental Albumin
Authors: C. Jack Bark
Journal: JAMA (1969)

<h3>To the Editor:—</h3> A spectacular rise in serum alkaline phosphatase to a level of 160 Bodansky units was seen in a patient with liver disease following the administration of serum albumin. The high enzyme activity was traced to albumin prepared from placentas. The latter are known to be rich in heat stable alkaline phosphatase. The patient's serum alkaline phosphatase gradually fell to a normal level following cessation of albumin therapy. The presence of large amounts of alkaline phosphatase in placental albumin is not widely known and could lead to erroneous interpretation of laboratory findings. Manufacturers of placental serum albumin should assay their product for alkaline phosphatase and this information should be included with the product. A similar observation has been reported from Australia by Neale et al (<i>Med J Aust</i><b>2</b>:684, 1963).