tbuckley/cabot-search huggingface dataset:
Airway responsiveness to adenosine 5' monophosphate following inhalation of hypertonic saline
Authors: SP O'Hickey, PJ Rees, TH Lee
Journal: European Respiratory Journal (1989)

We wished to determine whether the refractory period after hypertonic saline (HS) challenge is due to mast cell mediator depletion. Therefore, the airway responsiveness to adenosine 5' monophosphate (AMP), which induces bronchoconstriction via mast cell histamine release, was determined after the inhalation of HS aerosol. Nine asthmatic subjects attended the laboratory on three occasions. On day 1 HS challenge was performed followed one hour later by a second HS challenge. On day 2 an AMP challenge was performed. On day 3 an HS challenge was performed followed one hour later by an AMP challenge. Airway responsiveness (PD35 sGaw) to an initial HS challenge ranged from 12 to 315 l of aerosol (mean 47 l). Airway responsiveness to a second HS challenge ranged from 8 to 800 l (mean 102 l p = 0.035, n = 9). Airway responsiveness to AMP increased from 0.44 to 14.0 mumol (mean 2.37 mumol) at baseline to 0.3 to 15.5 (mean 1.3 mumol) (p = 0.05) after HS challenge. There was a linear correlation between baseline AMP responsiveness and baseline HS responsiveness (r = 0.911, p = 0.001). There was no correlation between the degree of refractoriness and the change in AMP responsiveness (r = 0.1, p = 0.9). Thus airway responsiveness to AMP increased significantly after inhalation of HS aerosol and this increase was independent of refractory behaviour. Our results suggest that the refractory period to HS is not due to mediator depletion.
Antagonism of PDGF-D by Human Antibody CR002 Prevents Renal Scarring in Experimental Glomerulonephritis
Authors: Tammo Ostendorf, Song Rong, Peter Boor, Stefanie Wiedemann, Uta Kunter, Ulrike Haubold, Claudia R.C. van Roeyen, Frank Eitner, Hiroshi Kawachi, Gary Starling, Enrique Alvarez, Glennda Smithson, Ju[Combining Diaeresis]rgen Floege
Journal: Journal of the American Society of Nephrology (2006)

Glomerular mesangial cell proliferation and/or matrix accumulation characterizes many progressive renal diseases. PDGF-D was identified recently as a novel mediator of mesangial cell proliferation in vitro and in vivo. This study investigated the long-term consequences of PDGF-D inhibition in vivo. Rats with progressive mesangioproliferative glomerulonephritis (uninephrectomy plus anti-Thy-1.1 antibody) received the PDGF-D-neutralizing, fully human mAb CR002 on days 3, 10, and 17 after disease induction. Glomerular mesangioproliferative changes on day 10 were significantly reduced by anti-PDGF-D treatment as compared with control antibody. Eight weeks after disease induction, anti-PDGF-D therapy significantly ameliorated focal segmental glomerulosclerosis, podocyte damage (de novo desmin expression), tubulointerstitial damage, and fibrosis as well as the accumulation of renal interstitial matrix including type III collagen and fibronectin. Treatment with anti-PDGF-D also reduced the cortical infiltration of monocytes/macrophages on day 56, possibly related to lower renal cortical complement activation (C5b-9 deposition) and/or reduced epithelial-to-mesenchymal transition (preserved cortical expression of E-cadherin and reduced expression of vimentin and alpha-smooth muscle actin). In conclusion, these data provide evidence for a causal role of PDGF-D in the pathogenesis of renal scarring and point to a new therapeutic approach to progressive mesangioproliferative renal disease.
The Immunodominant Antigen of an Ultraviolet-induced Regressor Tumor Is Generated by a Somatic Point Mutation in the DEAD Box Helicase p68
Authors: Purnima Dubey, Ronald C. Hendrickson, Stephen C. Meredith, Christopher T. Siegel, Jeffrey Shabanowitz, Jonathan C.A. Skipper, Victor H. Engelhard, Donald F. Hunt, Hans Schreiber
Journal: The Journal of Experimental Medicine (1997)

The genetic origins of CD8+ T cell–recognized unique antigens to which mice respond when immunized with syngeneic tumor cells are unknown. The ultraviolet light-induced murine tumor 8101 expresses an H-2Kb-restricted immunodominant antigen, A, that induces cytolytic CD8+ T cells in vivo A+ 8101 cells are rejected by naive mice while A− 8101 tumor cells grow. To identify the antigen H-2Kb molecules were immunoprecipitated from A+ 8101 cells and peptides were eluted by acid. The sensitizing peptide was isolated by sequential reverse-phase HPLC and sequenced using microcapillary HPLC-triple quadruple mass spectrometry. The peptide, SNFVFAGI, matched the sequence of the DEAD box protein p68 RNA helicase except for a single amino acid substitution, caused by a single nucleotide change. This mutation was somatic since fibroblasts from the mouse of tumor origin expressed the wild-type sequence. The amino acid substitution created an anchor for binding of the mutant peptide to H-2Kb. Our results are consistent with mutant p68 being responsible for rejection of the tumor. Several functions of p68, which include nucleolar assembly and inhibition of DNA unwinding, may be mediated through its IQ domain, which was altered by the mutation. This is the first description of a somatic tumor–specific mutation in the coding region of a nucleic acid helicase.
Chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular remodelling
Authors: S. Schafer, P. Ellinghaus, W. Janssen, F. Kramer, K. Lustig, H. Milting, R. Kast, M. Klein
Journal: Cardiovascular Research (2009)

Inhibition of phosphodiesterase 5 (PDE5) decreases pulmonary pressure and improves symptoms in patients with pulmonary arterial hypertension. It is unclear however, whether inhibition of PDE5 can prevent myocardial remodelling during right-ventricular pressure overload.Right-ventricular pressure overload was produced in male rats in a pulmonary hypertension model (monocrotaline 60 mg/kg s.c.) or by surgical pulmonary artery banding. PDE5 inhibition using oral sildenafil (50 mg/kg/day in drinking water) or placebo was initiated 14 days after monocrotaline treatment and continued for 14 days until final examination. In the pulmonary artery banding groups, rats were treated with sildenafil (50 mg/kg/day) or placebo for 21 days following surgical pulmonary artery banding. At the final experiments, right-ventricular haemodynamics were measured and remodelling was analysed using histological, biochemical, and gene expression markers. Both monocrotaline and pulmonary artery banding increased right-ventricular systolic pressure to approximately 80 mmHg. In parallel, both interventions induced markers of hypertrophy (upregulation of natriuretic peptides, increase in myocyte diameter) and fibrosis (upregulation of collagen types 1A2 and 3A1) as well as mRNA expression of the tissue inhibitor of matrix metalloproteases 1 and osteopontin in the right ventricle. In monocrotaline model, sildenafil decreased pulmonary pressure, reduced right-ventricular hypertrophy, and prevented fibrosis marker gene upregulation. After pulmonary artery banding, in contrast, sildenafil increased markers of myocardial remodelling and right-ventricular myocyte diameter.Sildenafil prevents myocardial remodelling in pulmonary hypertension through an indirect action via right-ventricular unloading.
Very low-density lipoprotein/lipo-viro particles reverse lipoprotein lipase-mediated inhibition of hepatitis C virus infection via apolipoprotein C-III
Authors: Hung-Yu Sun, Chun-Chieh Lin, Jin-Ching Lee, Shainn-Wei Wang, Pin-Nan Cheng, I-Chin Wu, Ting-Tsung Chang, Ming-Derg Lai, Dar-Bin Shieh, Kung-Chia Young
Journal: Gut (2012)

<h3>Objective</h3> Circulating hepatitis C virus (HCV) virions are associated with triglyceride-rich lipoproteins, including very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), designated as lipo-viro-particles (LVPs). Previous studies showed that lipoprotein lipase (LPL), a key enzyme for hydrolysing the triglyceride in VLDL to finally become LDL, may suppress HCV infection. This investigation considers the regulation of LPL by lipoproteins and LVPs, and their roles in the LPL-mediated anti-HCV function. <h3>Design</h3> The lipoproteins were fractionated from normolipidemic blood samples using iodixanol gradients. Subsequent immunoglobulin-affinity purification from the canonical VLDL and LDL yielded the corresponding VLDL-LVP and LDL-LVP. Apolipoprotein (apo) Cs, LPL activity and HCV infection were quantified. <h3>Results</h3> A higher triglyceride/cholesterol ratio of LDL was found more in HCV-infected donors than in healthy volunteers, and the triglyceride/cholesterol ratio of LDL-LVP was much increased, suggesting that the LPL hydrolysis of triglyceride may be impaired. VLDL, VLDL-LVP, LDL-LVP, but not LDL, suppressed LPL lipolytic activity, which was restored by antibodies that recognised apoC-III/-IV and correlated with the steadily abundant apoC-III/-IV quantities in those particles. In a cell-based system, treatment with VLDL and LVPs reversed the LPL-mediated inhibition of HCV infection in apoC-III/-IV-dependent manners. A multivariate logistic regression revealed that plasma HCV viral loads correlated negatively with LPL lipolytic activity, but positively with the apoC-III content of VLDL. Additionally, apoC-III in VLDL was associated with a higher proportion of HCV-RNA than was IgG. <h3>Conclusion</h3> This study reveals that LPL is an anti-HCV factor, and that apoC-III in VLDL and LVPs reduces the LPL-mediated inhibition of HCV infection.
Human erythrocyte protein 4.1 is a phosphatidylserine binding protein.
Authors: A C Rybicki, R Heath, B Lubin, R S Schwartz
Journal: Journal of Clinical Investigation (1988)

The aminophospholipids phosphatidylethanolamine (PE) and phosphatidylserine (PS) are the major phospholipids contained in the cytoplasmic leaflet of the human erythrocyte (RBC) plasma membrane and are largely confined to that leaflet over the entire RBC lifespan. In particular, PS, which comprises approximately 13% of total RBC membrane phospholipids, is normally restricted entirely to the cytoplasmic leaflet. However, molecular mechanisms that regulate this asymmetric distribution of phospholipids are largely unknown. We examined elliptocytic RBCs that completely lacked protein 4.1 (HE [4.1 degrees]), but contained normal amounts of all other peripheral membrane proteins, and found approximately 10% of total membrane PS was accessible in the exoplasmic leaflet of these membranes. Inside out vesicles (IOVs) derived from HE [4.1 degrees] RBCs bound fewer PS liposomes than did IOVs derived from normal RBCs. Normal IOVs that were depleted of proteins 2.1 (ankyrin), 4.1, and 4.2 bound fewer PS liposomes similar to HE [4.1 degrees] IOVs, and repletion with protein 4.1 restored PS liposome binding to control levels. Addition of purified protein 4.1 to PS liposomes resulted in saturable binding with the extent of binding being proportional to the liposome PS content. Our data suggests that human RBC protein 4.1 is a PS binding protein and may be involved in the molecular mechanisms that stabilize PS in the cytoplasmic leaflet of the human RBC plasma membrane.
MECHANISMS UNDERLYING BINDING OF IMMUNE COMPLEXES TO MACROPHAGES
Authors: Julia M. Phillips-Quagliata, Bernard B. Levine, Franco Quagliata, Jonathan W. Uhr
Journal: The Journal of Experimental Medicine (1971)

The mechanism of binding of immune complexes to macrophages was investigated using purified antibody and haptens of different valences. Antibody alone bound to macrophages; enhancement of binding occurred when polyvalent and divalent haptens were present at equivalence but did not occur in great antigen excess. Monovalent hapten did not increase the binding of antibody at any concentration ratio tried, though it inhibited the enhancement due to oligovalent hapten. Ultracentrifuged normal rabbit globulin also inhibited the binding of complexes indicating the presence of exposed binding sites on the uncomplexed molecules. Complexes bound more strongly than antibody alone as determined from elution studies. These results support the hypothesis that the enhancement of antibody binding to macrophages in the presence of antigen is due to increased energy of binding resulting from summation of individual binding sites already exposed on the antibody molecules. It was also possible, by saturating the macrophages with gamma globulin, to estimate the number of binding sites per cell; this was calculated to be approximately 2 million per alveolar macrophage.
Inference of protein function and protein linkages in Mycobacterium tuberculosis based on prokaryotic genome organization: a combined computational approach
Authors: Michael Strong, Parag Mallick, Matteo Pellegrini, Michael J Thompson, David Eisenberg
Journal: Genome biology (2003)

The genome of Mycobacterium tuberculosis was analyzed using recently developed computational approaches to infer protein function and protein linkages. We evaluated and employed a method to infer genes likely to belong to the same operon, as judged by the nucleotide distance between genes in the same genomic orientation, and combined this method with those of the Rosetta Stone, Phylogenetic Profile and conserved Gene Neighbor computational methods for the inference of protein function.
Reduced Hippocampal Activation During Encoding and Recognition of Words in Schizophrenia Patients
Authors: Frank Jessen, Lukas Scheef, Lars Germeshausen, Youlha Tawo, Martin Kockler, Kai-Uwe Kuhn, Wolfgang Maier, Hans H Schild, Reinhard Heun
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: In patients with schizophrenia, impaired hippocampal activation either during encoding or recognition tasks has been observed in a few functional imaging experiments. In this fMRI study, the authors report results of word encoding and recognition in schizophrenia patients and healthy comparison subjects, with a special focus on correcting for behavioral recognition success in order to prevent a bias related to lower task performance in the schizophrenia patients. METHOD: The verbal encoding and recognition tasks were both first analyzed irrespective of recognition success. In a second analysis, recognition success was included in the block-designed encoding task as a covariate of no interest, and incorrectly classified items were rejected from the analysis of the event-related recognition task. RESULTS: Patients performed poorer on the recognition task than the comparison subjects. Bilateral hippocampal activation during encoding and recognition was observed in both groups. Right hippocampal activation in patients during recognition became significant only after exclusion of wrongly classified items. Group comparison revealed greater activation in the healthy comparison subjects in the left anterior hippocampus during encoding and bilaterally during recognition. Greater bilateral hippocampal activation in the healthy subjects and greater activation in the right anterior hippocampus in the schizophrenic patients were revealed after presentation of novel words, which were intermixed with previously encoded words in the recognition task. After exclusion of incorrectly classified items, the differences in the right hippocampus remained significant. CONCLUSIONS: This study provides evidence for disturbed hippocampal function during verbal encoding and recognition in patients with schizophrenia. It extends previous studies by correcting for the possible confound of differences in behavioral task performance. This approach further supports the concept of hippocampal dysfunction in schizophrenia.
The influence of corneocyte overlap on the measurement of stratum corneum cell layers
Authors: C.E.H. Grattan, W.A.D. Griffiths
Journal: British Journal of Dermatology (1985)

Journal Article The influence of corneocyte overlap on the measurement of stratum corneum cell layers Get access C.E.H. Grattan, C.E.H. Grattan Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8HW, U.K. Search for other works by this author on: Oxford Academic Google Scholar W.A.D. Griffiths W.A.D. Griffiths St John's Hospital for Diseases of the Skin, 5 Lisle Street, London WC2H 7BJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue 2, 1 August 1985, Pages 247–249, https://doi.org/10.1111/j.1365-2133.1985.tb02073.x Published: 01 August 1985
Collagenous colitis: constipation or diarrhoea?
Authors: Z Barta
Journal: Gut (2003)

As an axiom, collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa.1 Various case presentations in the literature have reported that frequent watery diarrhoea introduces the clinical picture of collagenous colitis and intermittent or continuous diarrhoea can remain.2 On the other hand, numerous cases never suffer from episodes of watery diarrhoea but suffer from chronic constipation. Can we call into question the “incontestable” definition? Bonderup et al investigated the clinical and histological effect of oral budesonide in the treatment of collagenous colitis in 20 patients and concluded that budesonide is …
Evidence-based journal watch
Authors: Martin P Schwellnus
Journal: British Journal of Sports Medicine (2011)

▶ Knapik JJ, Trone DW, Swedler DI, et al. Injury reduction effectiveness of assigning running shoes based on plantar shape in Marine Corps basic training. Am J Sports Med 2010;38:1759–67.[OpenUrl][1][Abstract/FREE Full Text][2] ### Background Running shoe manufacturers designed and marketed running shoes according to motion control, stability and cushioning – the practice is to assign shoes according to plantar shapes (low, normal and high) and this is done in order to reduce the risk of injuries. ### Research question/s Does the practice of assigning running shoes according to plantar shape reduce the risk of injury during Marine Corps basic training? ### Methodology [1]: {openurl}?query=rft.jtitle%253DAm%2BJ%2BSports%2BMed%26rft_id%253Dinfo%253Adoi%252F10.1177%252F0363546510369548%26rft_id%253Dinfo%253Apmid%252F20576837%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=amjsports&resid=38/9/1759&atom=%2Fbjsports%2F45%2F14%2F1167.atom
Pressure-dependent membrane depolarization in cat middle cerebral artery.
Authors: D R Harder
Journal: Circulation Research (1984)

This study was undertaken to examine the effect of increasing transmural pressure on membrane electrical properties of cat middle cerebral arterial muscle. Middle cerebral arteries were removed from the cat brain, cannulated, and prepared so that transmural pressure within a segment could be manipulated. Intracellular membrane potential was recorded with glass microelectrodes at various transmural pressures. There was a positive slope relating changes in intracellular membrane potential as a function of transmural pressure with a correlation coefficient of 0.79. Blockade of nerve excitation with tetrodotoxin and inhibition of alpha-adrenergic receptors with phentolamine not only did not block the pressure-induced depolarization, but increased the slope of the intracellular membrane potential vs. pressure relationship. This slope was increased upon elevation of extracellular calcium concentration from 2.5 to 4.0 mM and was significantly reduced upon reduction of extracellular calcium concentration to 0.5 mM. When arterial preparations were equilibrated at 0 mm Hg prior to pressurization, action potentials were recorded only when pressure was initially elevated, while a sustained depolarization was recorded during the pressure plateau. However, when arteries were equilibrated at a transmural pressure of 100 mm Hg for 90 minutes, spontaneous action potentials were recorded which increased in frequency as a function of pressure until they were inactivated when intracellular membrane potential approached -30 mV at high transmural pressures. Photomicrographs demonstrated that these vessels either maintained or decreased diameter upon pressurization. These findings provide a cellular mechanism for myogenic regulation of cerebral arterial diameter.
Altered Pituitary-Adrenal Axis Responses to Provocative Challenge Tests in Adult Survivors of Childhood Abuse
Authors: C Heim, D J Newport, R Bonsall, A H Miller, C B Nemeroff
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Early adverse life events may predispose individuals to the development of mood and anxiety disorders in adulthood, perhaps by inducing persistent changes in corticotropin-releasing factor (CRF) neuronal systems. The present study sought to evaluate pituitary-adrenal responses to standard hypothalamic-pituitary-adrenal axis challenge tests in adult female survivors of childhood abuse with and without major depressive disorder. METHOD: Plasma ACTH and cortisol responses to the administration of 1 μg/kg ovine CRF and plasma cortisol responses to the administration of 250 μg ACTH1–24 were measured in healthy women without early life stress (N=20), women with childhood abuse without major depressive disorder (N=20), women with childhood abuse and major depressive disorder (N=15), and women with major depression but no early life stress (N=11). RESULTS: Abused women without major depressive disorder exhibited greater than usual ACTH responses to CRF administration, whereas abused women with major depressive disorder and depressed women without early life stress demonstrated blunted ACTH responses. In the ACTH1–24 stimulation test, abused women without major depressive disorder exhibited lower baseline and stimulated plasma cortisol concentrations. Abused women with comorbid depression more often suffered from posttraumatic stress disorder and reported more recent life stress than abused women without major depressive disorder. CONCLUSIONS: These findings suggest sensitization of the anterior pituitary and counterregulative adaptation of the adrenal cortex in abused women without major depressive disorder. On subsequent stress exposure, women with a history of childhood abuse may hypersecrete CRF, resulting in down-regulation of adenohypophyseal CRF receptors and symptoms of depression and anxiety.
Nucleolar Binding Sequences of the Ribosomal Protein S6e Family Reside in Evolutionary Highly Conserved Peptide Clusters
Authors: S. Kundu-Michalik, M.-A. Bisotti, E. Lipsius, A. Bauche, A. Kruppa, T. Klokow, G. Kammler, J. Kruppa
Journal: Molecular Biology and Evolution (2008)

Proteomic analyses of the nucleolus have revealed almost 700 functionally diverse proteins implicated in ribosome biogenesis, nucleolar assembly, and regulation of vital cellular processes. However, this nucleolar inventory has not unveiled a specific consensus motif necessary for nucleolar binding. The ribosomal protein family characterized by their basic nature should exhibit distinct binding sequences that enable interactions with the rRNA precursor molecules facilitating subunit assembly. We succeeded in delineating 2 minimal nucleolar binding sequences of human ribosomal protein S6 by fusing S6 cDNA fragments to the 5' end of the LacZ gene and subsequently detecting the intracellular localization of the beta-galactosidase fusion proteins. Nobis1 (nucleolar binding sequence 1), comprising of 4 highly conserved amino acid clusters separated by glycine or proline, functions independently of the 3 authentic nuclear localization signals (NLSs). Nobis2 consists of 2 conserved peptide clusters and requires the authentic NLS2 in its native context. Similarly, we deduced from previous publications that the single Nobis of ribosomal protein S25 is also highly conserved. The functional protein domain organization of the ribosomal protein S6e family consists of 3 modules: NLS, Nobis, and the C-terminal serine cluster of the phosphorylation sites. This modular structure is evolutionary conserved in vertebrates, invertebrates, and fungi. Remarkably, nucleolar binding sequences of small and large ribosomal proteins reside in peptide clusters conserved over millions of years.