tbuckley/cabot-search huggingface dataset:
Compartmentalized Production of CCL17 In Vivo
Authors: Judith Alferink, Ivo Lieberam, Wolfgang Reindl, Andrea Behrens, Susanne Weiß, Norbert Hüser, Klaus Gerauer, Ralf Ross, Angelika B. Reske-Kunz, Parviz Ahmad-Nejad, Hermann Wagner, Irmgard Förster
Journal: The Journal of Experimental Medicine (2003)

Dendritic cells (DCs)**Abbreviations used in this paper: BM, bone marrow; CHS, contact hypersensitivity; cLN, cutaneous lymph node; CRP, C-reactive protein; DC, dendritic cell; DNFB, dinitrofluorobenzene; EGFP, enhanced green fluorescent protein; LC, Langerhans cell; LP, lamina propria; MACS, magnetic-activated cell sorting; mLN, mesenteric lymph node; ODN, oligodeoxynucleotide; PFA, paraformaldehyde; PP, Peyer's patch; TLR, Toll-like receptor; TRITC, tetramethylrhodamine-5-(and-6-)-isothiocyanate. fulfill an important regulatory function at the interface of the innate and adaptive immune system. The thymus and activation-regulated chemokine (TARC/CCL17) is produced by DCs and facilitates the attraction of activated T cells. Using a fluorescence-based in vivo reporter system, we show that CCL17 expression in mice is found in activated Langerhans cells and mature DCs located in various lymphoid and nonlymphoid organs, and is up-regulated after stimulation with Toll-like receptor ligands. DCs expressing CCL17 belong to the CD11b+CD8−Dec205+ DC subset, including the myeloid-related DCs located in the subepithelial dome of Peyer's patches. CCL17-deficient mice mount diminished T cell–dependent contact hypersensitivity responses and display a deficiency in rejection of allogeneic organ transplants. In contrast to lymphoid organs located at external barriers of the skin and mucosa, CCL17 is not expressed in the spleen, even after systemic microbial challenge or after in vitro stimulation. These findings indicate that CCL17 production is a hallmark of local DC stimulation in peripheral organs but is absent from the spleen as a filter of blood-borne antigens.
ΔFosB in brain reward circuits mediates resilience to stress and antidepressant responses
Authors: Vincent Vialou, Alfred J Robison, Quincey C LaPlant, Herbert E Covington, David M Dietz, Yoshinori N Ohnishi, Ezekiell Mouzon, Augustus J Rush, Emily L Watts, Deanna L Wallace, Sergio D Iñiguez, Yoko H Ohnishi, Michel A Steiner, Brandon L Warren, Vaishnav Krishnan, Carlos A Bolaños, Rachael L Neve, Subroto Ghose, Olivier Berton, Carol A Tamminga, Eric J Nestler
Journal: Nature Neuroscience (2010)
Urinary Aquaporin 2 and Calciuria Correlate with the Severity of Enuresis in Children
Authors: GIOVANNA VALENTI, ANTONIA LAERA, GIUSEPPE PACE, GABRIELLA ACETO, MARIA L. LOSPALLUTI, ROSA PENZA, FRANCESCO P. SELVAGGI, MARIA L. CHIOZZA, MARIA SVELTO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. This study examined the hypothesis that nocturnal enuresis might be paralleled by aquaporin 2 (AQP2) urinary excretion. Eighty children who experienced nocturnal enuresis were studied and compared with 9 healthy children. The 24-h urine samples were divided into two portions: night collections and day collections. Creatinine equivalents of urine samples from each patient were analyzed by Western blotting. AQP2 levels were semiquantified by densitometric scanning and reported as a ratio between the intensity of the signal in the day urine sample versus the night urine sample (D/N AQP2 ratio). The D/N AQP2 ratio was 0.59 ± 0.11 ( n = 9) in healthy children and increased to 1.27 ± 0.24 ( n = 10) in a subpopulation of enuretic children who had low nocturnal vasopressin levels. In enuretic children who displayed hypercalciuria and had normal vasopressin levels, the D/N AQP2 ratio was 1.05 ± 0.27 ( n = 8). These data indicate that reduced secretion of vasopressin and absorptive hypercalciuria are independently associated with an approximately twofold increase in the urinary D/N AQP2 ratio. When low nocturnal vasopressin levels were associated with hypercalciuria, a nearly threefold increase in the D/N AQP2 ratio was observed (1.67 ± 0.41, n = 11). In addition, in all enuretic patients tested, the urinary D/N AQP2 ratio correlates perfectly with the severity of the disorder (nocturnal polyuria). The findings reported in this article indicate that urinary AQP2 correlates with the severity of enuresis in children.
Evaluation of continuous infusion low‐dose 5‐azacytidine in the treatment of myelodysplastic syndromes
Authors: Christopher R. Chitambar, Joseph A. Libnoch, William G. Matthaeus, Robert C. Ash, Paul S. Ritch, Tom Anderson
Journal: American Journal of Hematology (1991)

Abstract The treatment of myelodysplastic syndromes (MDS) is both difficult and controversial. In the current study, we evaluated the efficacy of low‐dose 5‐azacytidine in the treatment of this disorder. Fifteen patients with MDS were entered on study to be treated with 5‐azacytidine by continuous intravenous infusion for 14 days. Doses of the drug ranged from 10 mg/m 2 /day to 35 mg/m 2 /day, with most patients receiving 16.5 mg/m 2 /day. In two patients, the drug was stopped early in the course of treatment because of thrombocytopenia. Thirteen patients completed therapy according to protocol. Three of 13 patients demonstrated a partial response to therapy. Of these three patients, one had an increase in platelet and absolute neutrophil counts, while the other two no longer required support with red cell transfusions. The drug was well tolerated and significant myelosuppression did not occur in most patients. Low‐dose 5‐azacytidine appears to have activity in the treatment of primary MDS and future studies should consider evaluation of this drug in combination with hematopoietic growth factors.
Primary Visual Cortex: Awareness and Blindsight
Authors: David A. Leopold
Journal: Annual Review of Neuroscience (2012)

The primary visual cortex (V1) is the principal telencephalic recipient of visual input in humans and monkeys. It is unique among cortical areas in that its destruction results in chronic blindness. However, certain patients with V1 damage, though lacking visual awareness, exhibit visually guided behavior: blindsight. This phenomenon, together with evidence from electrophysiological, neuroimaging, and psychophysical experiments, has led to speculation that V1 activity has a special or direct role in generating conscious perception. To explore this issue, this article reviews experiments that have used two powerful paradigms—stimulus-induced perceptual suppression and chronic V1 ablation—each of which disrupts the ability to perceive salient visual stimuli. Focus is placed on recent neurophysiological, behavioral, and functional imaging studies from the nonhuman primate that shed light on V1's role in conscious awareness. In addition, anatomical pathways that relay visual information to the cortex during normal vision and in blindsight are reviewed. Although the critical role of V1 in primate vision follows naturally from its position as a bottleneck of visual signals, little evidence supports its direct contribution to visual awareness.
Pilot Study of Neoadjuvant Treatment with Erlotinib in Nonmetastatic Head and Neck Squamous Cell Carcinoma
Authors: Fabienne Thomas, Philippe Rochaix, Adil Benlyazid, Jérôme Sarini, Michel Rives, Jean Louis Lefebvre, Ben C. Allal, Frédéric Courbon, Etienne Chatelut, Jean-Pierre Delord
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To determine the safety and efficacy of erlotinib given as neoadjuvant treatment in patients with head and neck squamous cell carcinoma (HNSCC). Further objectives were to identify markers of response to erlotinib and to assess the pharmacodynamic effects of erlotinib in tumor cells. Experimental Design: Patients with locally advanced nonmetastatic HNSCC were treated with erlotinib 150 mg daily pending surgical management. Tumor samples were collected before and after erlotinib treatment and were analyzed using immunohistochemistry. Epidermal growth factor receptor copy number was determined in tumors using CISH analysis. Results: Between November 2003 and December 2005, 35 patients were included in the study. Neoadjuvant treatment with erlotinib in HNSCC patients was well tolerated and did not necessitate modification to routine surgical procedures. Among 31 evaluable patients, erlotinib was given for a median of 20 days. At the time of surgery, tumor shrinkage was observed in nine patients (29%). Immunohistochemistry analyses were done for 31 patients and showed a decrease in phosphorylated tyrosine residues and phosphorylated erk immunostaining after erlotinib treatment. In a retrospective analysis, baseline p21waf expression in the basal-like cell layer was statistically positively correlated with clinical response to treatment. Epidermal growth factor receptor copy number did not correlate with response to erlotinib. Conclusion: Neoadjuvant treatment of HNSCC with erlotinib was well tolerated. Baseline p21waf expression was associated with response to erlotinib and so might be useful as a tool to select patients for erlotinib therapy in this setting.
Cost of Care for Patients in Cancer Clinical Trials
Authors: Bruce H. Fireman, Louis Fehrenbacher, Elisabeth P. Gruskin, G. Thomas Ray
Journal: JNCI Journal of the National Cancer Institute (2000)

Information on the costs of medical care for patients enrolled in clinical trials is needed by policymakers evaluating ways to facilitate clinical research in a managed care environment. We examined the direct costs of medical care for patients enrolled in cancer clinical trials at a large health maintenance organization (HMO).Costs for 135 patients who entered 22 cancer clinical trials (including 12 breast cancer trials) at Kaiser Permanente in Northern California, from 1994 through 1996 were compared with costs for 135 matched control subjects who were not enrolled in such trials. Cancer registry data and medical charts were used in matching the control subjects to the trial enrollees with respect to cancer site, stage, date of diagnosis, age, sex, and trial eligibility. The direct costs of medical care were compared between trial enrollees and the control subjects for a 1-year period, with data on costs and utilization of services obtained from Kaiser Permanente databases and medical charts.Mean 1-year costs for the enrollees in trials were 10% higher than those for the control subjects ($17 003 per enrollee compared with $15 516 per control subject; two-sided P =.011). The primary component of this difference was a $1376 difference in chemotherapy costs ($4815 per trial enrollee versus $3439 per control subject; two-sided P<.001). Costs for the 11 enrollees in trials that had a bone marrow transplant (BMT) arm were approximately double the costs for their matched control subjects (borderline significance: two-sided P=.054). The $15 041 mean cost for the enrollees in trials without BMT was similar to the $15 186 mean cost for their matched control subjects.Participation in cancer clinical trials at a large HMO did not result in substantial increases in the direct costs of medical care.
SUBCLINICAL VITAMIN DEFICIENCY V. THE ASSAY OF SUBCLINICAL THIAMIN DEFICIENCY
Authors: MILDRED CARLEEN HULSE, M.A., NORMAN WEISSMAN, PH.D., ELMER STOTZ, PH.D., MARSHALL CLINTON, M.D., JOSEPH W. FERREBEE, M.D.
Journal: Annals of Internal Medicine (1944)

ExcerptINTRODUCTIONThe assay of subclinical thiamin deficiency is primarily a problem in defining changes in thiamin nutrition before signs or symptoms of deficiency make their appearance. Accomplishment of this end presupposes a knowledge of normal thiamin nutrition; that is, normal extracellular and intracellular thiamin concentrations, and the size and sequence of variation in these values which may precede the occurrence of clinical deficiency.1The purpose of the present study is to determine whether measurable changes in either extracellular or intracellular thiamin concentrations occur in subclinical thiamin deficiency. For comparison, observations are also reported on thiamin excretion and on pyruvate metabolism....
REMARKS ON THE VALUE OF THE SIGMOIDOSCOPE IN THE DIAGNOSIS BETWEEN PRIMARY AND SECONDARY COLITIS
Authors: P. L. Mummery
Journal: BMJ (1905)

THE SIGMOIDOSOOPE IN OOLITIB.[DEc. 23, 19o.which was connected with the heating apparatus beneath the floor.Every person who entered the operating theatre had to take off his coat and wear a sterilized one, and also had to wear big rubber boots In order to complete the precaution against the introduction of stray pathogenic organisms into the operating room.Lastly, we were incarcerated for a few minutes between two doors in the wall of the operation theatre whilst a current of sterilized air was passed over us.By taking all the above precautions Professor Iversen was able to prove that the gospel of surgical cleanliness could be observed without the use of antiseptics in clean operations.Modern operating theatres in our public hospitals are built in such an expensive fashion that it is not possible for the middle and upper classes to get their operations done under such palatial surroundings.A hundred and fifty years ago it was only the well-to-do who could command the servicts of a medical mau; to-day it is only the poor and the working man who gets the best places in which modern operations can be performed according to present-day ideals.The fallacy of these high ideals is shown by the result of operations in private houses.
Increased Fibulin-5 and Elastin in S100A4/Mts1 Mice With Pulmonary Hypertension
Authors: Sandra L. Merklinger, Roger A. Wagner, Edda Spiekerkoetter, Aleksander Hinek, Russell H. Knutsen, M. Golam Kabir, Kavin Desai, Shelby Hacker, Lingli Wang, Gordon M. Cann, Noona S. Ambartsumian, Eugene Lukanidin, Daniel Bernstein, Mansoor Husain, Robert P. Mecham, Barry Starcher, Hiromi Yanagisawa, Marlene Rabinovitch
Journal: Circulation Research (2005)

Transgenic mice overexpressing the calcium binding protein, S100A4/Mts1, occasionally develop severe pulmonary vascular obstructive disease. To understand what underlies this propensity, we compared the pulmonary vascular hemodynamic and structural features of S100A4/Mts1 with control C57Bl/6 mice at baseline, following a 2-week exposure to chronic hypoxia, and after 1 and 3 months "recovery" in room air. S100A4/Mts1 mice had greater right ventricular systolic pressure and right ventricular hypertrophy at baseline, which increased further with chronic hypoxia and was sustained after 3 months "recovery" in room air. These findings correlated with a heightened response to acute hypoxia and failure to vasodilate with nitric oxide or oxygen. S100A4/Mts1 mice, when compared with C57Bl/6 mice, also had impaired cardiac function judged by reduced ventricular elastance and decreased cardiac output. Despite higher right ventricular systolic pressures with chronic hypoxia, S100A4/Mts1 mice did not develop more severe PVD, but in contrast to C57Bl/6 mice, these features did not regress on return to room air. Microarray analysis of lung tissue identified a number of genes differentially upregulated in S100A4/Mts1 versus control mice. One of these, fibulin-5, is a matrix component necessary for normal elastin fiber assembly. Fibulin-5 was localized to pulmonary arteries and associated with thickened elastic laminae. This feature could underlie attenuation of pulmonary vascular changes in response to elevated pressure, as well as impaired reversibility.
Low dose intrarenal infusions of PGE2, PGI2, and 6-keto-PGE1 vasodilate the in vivo rat kidney.
Authors: E K Jackson, H T Heidemann, R A Branch, J F Gerkens
Journal: Circulation Research (1982)

The renal vascular effects of prostaglandin E2 (PGE2), 6-keto-PGE1, and PGI2 were investigated in indomethacin-pretreated rats. These prostanoids were infused directly into the left renal artery at rates ranging from 0.01 to 1.0 microgram/min, while renal blood flow and mean arterial blood pressure were constantly monitored. PGE2, 6-keto-PGE1, and PGI2 produced reductions in mean arterial blood pressure with threshold doses of 1.0, 0.3, and 0.03 microgram/min (P less than 0.01), respectively, and maximal vasodepressor responses of 18.9 +/- 4.3, 37.0 +/- 7.8, and 58.7 +/- 8.2 mm Hg (P less than 0.01), respectively. In addition, all three prostanoids caused a dose-related reduction in renal vascular resistance with a threshold dose of 0.01 microgram/min (P less than 0.05). The maximal reductions in renal vascular resistance were 2.59 +/- 0.52, 4.41 +/- 1.20, and 5.29 +/- 1.06 mm Hg/(ml per min) for PGE2, 6-keto-PGE1, and PGI2 (P less than 0.01), respectively. Whereas PGE2 an 6-keto-PGE1 produced dose-dependent increases in renal blood flow (maximal increases of 1.5 +/- 0.3 and 1.0 +/- 0.3 ml/min, respectively (P less than 0.01), PGI2 nonsignificantly increased renal blood flow at low doses and decreased renal blood flow at higher infusion rates (P less than 0.01). These data indicate that the in vivo rat kidney, similar to the kidneys of other species, is vasodilated by low doses of PGE2, PGI2, and 6-keto-PGE1.
Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators
Authors: T Piche, G Barbara, P Aubert, S Bruley des Varannes, R Dainese, J L Nano, C Cremon, V Stanghellini, R De Giorgio, J P Galmiche, M Neunlist
Journal: Gut (2008)

Growing evidence suggests that patients with irritable bowel syndrome (IBS) have increased intestinal permeability. In addition, mucosal soluble mediators are involved in the pathophysiology of pain in IBS. We aimed to investigate (1) paracellular permeability in colonic biopsies of patients with IBS; and (2) the ability of soluble factors from colonic biopsies to reproduce these alterations in vitro.Paracellular permeability in colonic biopsies of healthy subjects and patients with IBS was measured by mounting the biopsies in Ussing chambers. Cleared supernatant (SUP) of the culture from colonic biopsies was collected and applied to Caco-2 cells for 48 h. Paracellular permeability and transepithelial resistance (TER) were evaluated. mRNA expression of the tight junction proteins, zonula occludens (ZO)-1 and occludin, was assessed in colonic biopsies. Abdominal pain was assessed using a validated questionnaire.Permeability of colonic biopsies was significantly higher in patients with IBS compared to healthy subjects. These changes were associated with significantly lower expression of ZO-1 mRNA in biopsies of IBS as compared to healthy subjects. Compared to healthy subjects, SUP of IBS markedly reduced TER and significantly increased permeability in Caco-2 cells. SUP of IBS patients induced a significant decrease of ZO-1 mRNA in Caco-2 as compared to healthy subjects. SUP-induced increased paracellular permeability correlated with the severity of abdominal pain.Our study shows that colonic soluble mediators are able to reproduce functional (permeability) and molecular (ZO-1 mRNA expression) alterations observed in IBS patients. These findings might pave the way both to identify novel biomarkers as well as new therapeutic targets in IBS.
Exercise‐Induced Bronchoconstriction
Authors: J. M. Henriksen
Journal: Allergy (1986)

Statidardized exercise challenge tests, symptom scores and whole‐blood eosinophil and basophil counts were made before and during the pollen season in 32 children suffering from hay fever ( n = 16) or hay fever and asthma ( n = 16). All participants developed rhinitis symptoms during the season. The hay fever group showed in addition a significant seasonal increase in cough score (but in no other asthma symptom) and in circulating eosinophils ( P &lt; 0.01); mean exercise‐induced bronchoconstriction (EIB) did not change despite a slight increase in a few subjects. The asthma group showed seasonal increases in EIB ( P &lt; 0.001), asthma symptom score ( P &lt; 0.002), and total eosinophil count ( P &lt; 0.001) The increase in the latter was significantly higher ( P &lt; 0.05) than that in the hay fever group. The relative basophil count remained unchanged in both groups. In conclusion, the hay fever group and the asthma group could be clearly distinguished with respect to EIB during natural pollen exposure. The significantly higher increases in EIB and circulating eosinophils observed in the asthma group might possibly be due to greater pollen antigen sensitivity in the asthmatics.
Insight into the Diversity and Evolution of the Cryptomonad Nucleomorph Genome
Authors: C. E. Lane
Journal: Molecular Biology and Evolution (2005)

The cryptomonads are an enigmatic group of marine and freshwater unicellular algae that acquired their plastids through the engulfment and retention of a eukaryotic ("secondary") endosymbiont. Together with the chlorarachniophyte algae, the cryptomonads are unusual in that they have retained the nucleus of their endosymbiont in a miniaturized form called a nucleomorph. The nucleomorph genome of the cryptomonad Guillardia theta has been completely sequenced and with only three chromosomes and a total size of 551 kb, is a model of nuclear genome compaction. Using this genome as a reference, we have investigated the structure and content of nucleomorph genomes in a wide range of cryptomonad algae. In this study, we have sequenced nine new cryptomonad nucleomorph 18S ribosomal DNA (rDNA) genes and four heat shock protein 90 (hsp90) gene fragments, and using pulsed-field gel electrophoresis and Southern hybridizations, have obtained nucleomorph genome size estimates for nine different species. We also used long-range polymerase chain reaction to obtain nucleomorph genomic fragments from Hanusia phi CCMP325 and Proteomonas sulcata CCMP704 that are syntenic with the subtelomeric region of nucleomorph chromosome I in G. theta. Our results indicate that (1) the presence of three chromosomes is a common feature of the nucleomorph genomes of these organisms, (2) nucleomorph genome size varies dramatically in the cryptomonads examined, (3) unidentified cryptomonad species CCMP1178 has the largest nucleomorph genome identified to date at ∼845 kb, (4) nucleomorph genome size reductions appear to have occurred multiple times independently during cryptomonad evolution, (5) the relative positions of the 18S rDNA, ubc4, and hsp90 genes are conserved in three different cryptomonad genera, and (6) interchromosomal recombination appears to be rapidly changing the size and sequence of a repetitive subtelomeric region of the nucleomorph genome between the 18S rDNA and ubc4 loci. These results provide a glimpse into the genetic diversity of nucleomorph genomes in cryptomonads and set the stage for more comprehensive sequence-based studies in closely and distantly related taxa.