tbuckley/cabot-search huggingface dataset:
Lipopolysaccharide modulates the expression of alpha 1 proteinase inhibitor and other serine proteinase inhibitors in human monocytes and macrophages.
Authors: C Barbey-Morel, J A Pierce, E J Campbell, D H Perlmutter
Journal: The Journal of Experimental Medicine (1987)

alpha 1 Proteinase inhibitor (PI) is the principle inhibitor of neutrophil elastase, an enzyme that degrades many components of the extracellular matrix. Expression and regulation of alpha 1 PI, therefore, affects the delicate balance of elastase and antielastase, which is critical to turnover of connective tissue during homeostasis, tissue injury, and repair. In this study we show that expression of alpha 1 PI in human monocytes and macrophages is regulated during activation by LPS. LPS mediates a concentration- and time-dependent increase in the rate of synthesis of alpha 1 PI in mononuclear phagocytes. There is a 4.5-8.7-fold increase in functionally active inhibitor delivered to the cell culture fluid of monocytes. The effect of LPS is specific in that it is neutralized by an mAb to the lipid A moiety. The increase in expression of alpha 1 PI mediated by LPS occurs in the context of other specific changes in the expression of serine proteinase inhibitor genes in mononuclear phagocytes. There is an increase in the rate of synthesis of C1 inhibitor and a decrease in synthesis of alpha 2 macroglobulin. Regulation of alpha 1 PI by LPS is distinctive in that it is largely determined by a change in the efficiency of translation of alpha 1 PI mRNA. LPS has no effect on the rate of posttranslational processing and/or secretion of alpha 1 PI and, therein, causes greater intracellular accumulation of alpha 1 PI in mononuclear phagocytes from individuals with homozygous PiZZ alpha 1 PI deficiency.
Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function.
Authors: W D Steers, S Kolbeck, D Creedon, J B Tuttle
Journal: Journal of Clinical Investigation (1991)

Urethral obstruction produces increased voiding frequency (0.7 +/- 0.06 to 1.1 +/- 0.08 h-1) and hypertrophy of the urinary bladder (89 +/- 1.7 to 708 +/- 40 mg) with profound increments in the dimensions of afferent (4, 6) and efferent neurons (299 +/- 4.7 to 573 +/- 8.6 microns2) supplying this organ in the rat. We discovered that hypertrophied bladders of rat and human contain significantly more nerve growth factor (NGF) per milligram wet weight, protein, and DNA than normal bladders. The temporal correlation between NGF content, neuronal hypertrophy, and bladder weight was consistent with a role for this growth factor in the neurotrophic effects associated with obstruction. Autoimmunity to NGF abolished the hypertrophy of NGF-sensitive bladder neurons in the pelvic ganglion after obstruction. Relief of urethral obstruction reduced bladder size (349 +/- 78 mg), but neuronal hypertrophy (460.2 +/- 10.2 microns2) and elevated NGF levels were only partially reversed. Bladder hypertrophy (133 +/- 4.3 mg) induced by osmotic diuresis slightly increased ganglion cell area (365.2 +/- 6.1 microns2) and only doubled NGF content of the bladder. These findings provide important new evidence that parenchymal cells in the hypertrophied bladder can synthesize NGF and possibly other molecular messengers that act to alter the size and function of neurons in adult animals and man.
Evolution of primate ABO blood group genes and their homologous genes
Authors: N. Saitou, F. Yamamoto
Journal: Molecular Biology and Evolution (1997)

There are three common alleles (A, B, and O) at the human ABO blood group locus. We compared nucleotide sequences of these alleles, and relatively large numbers of nucleotide differences were found among them. These differences correspond to the divergence time of at least a few million years, which is unusually large for a human allelic divergence under neutral evolution. We constructed phylogenetic networks of human and nonhuman primate ABO alleles, and at least three independent appearances of B alleles from the ancestral A form were observed. These results suggest that some kind of balancing selection may have been operating at the ABO locus. We also constructed phylogenetic trees of ABO and their evolutionarily related alpha-1,3-galactosyltransferase genes, and the divergence time between these two families was estimated to be roughly 400 MYA.
Acute effect of inhaled bradykinin on tracheobronchial clearance in normal humans.
Authors: R Polosa, A Hasani, D Pavia, J E Agnew, C K Lai, S W Clarke, S T Holgate
Journal: Thorax (1992)

BACKGROUND: Bradykinin, a nonapeptide that contributes as a mediator to the pathogenesis of asthma, may affect lung mucociliary clearance, as it has been shown to be a potent secretagogue in canine airways and in human nasal mucosa in vivo. To evaluate this possibility the effect of inhaled bradykinin on mucociliary clearance has been studied in 10 healthy volunteers. METHODS: Subjects attended the laboratory on two occasions to take part in tracheobronchial clearance studies using a non-invasive radioisotopic technique. Inhalation of radioaerosol was followed 30 minutes later by inhalation of either bradykinin (8 mg/ml) or vehicle placebo in a randomised, double blind fashion. After each inhalation the number of coughs was recorded. Whole lung radioactivity was measured every half hour for six hours with two collimated scintillation counters, and a tracheobronchial clearance curve was plotted for each subject on each occasion. RESULTS: Mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first six hours (AUC0-6h), was greater in nine out of 10 subjects after inhalation of bradykinin than after placebo. The median values (range) for AUC0-6h were significantly reduced from 126% (78-232%)/h with placebo to 87% (51-133%)/h with bradykinin. CONCLUSION: It is concluded that acute exposure to inhaled bradykinin accelerates tracheobronchial clearance in normal human airways.
Inhibition of Neointima Hyperplasia of Mouse Vein Grafts by Locally Applied Suramin
Authors: Yanhua Hu, Yiping Zou, Hermann Dietrich, Georg Wick, Qingbo Xu
Journal: Circulation (1999)

Background —Saphenous vein grafts are widely used for aortocoronary bypass surgery as treatment for severe atherosclerosis and often are complicated by subsequent occlusion of the graft vessel. Methods and Results —We described a mouse model of venous bypass graft arteriosclerosis that can be effectively retarded by locally applied suramin, a growth factor receptor antagonist. Mouse isogeneic vessels of the vena cava veins pretreated with suramin were grafted end to end into the carotid arteries and enveloped with a mixture of suramin (1 mmol/L) and pluronic-127 gel. In the untreated group, vessel wall thickening was observed as early as 1 week after surgery and progressed to 4-fold and 10-fold the original thickness in grafted veins at 4 and 8 weeks, respectively. Pluronic-127 gel alone did not influence neointima formation. Suramin treatment reduced the neointima hyperplasia 50% to 70% compared with untreated controls. Immunohistochemical studies demonstrated that a significant proliferation of vascular smooth muscle cells (SMCs) constituted neointimal lesions between 4 and 8 weeks. The majority of SMCs expressed platelet-derived growth factor (PDGF) receptors-α and -β, which were significantly reduced by suramin treatment. In vitro studies indicated that suramin completely blocked PDGF receptor activation or phosphorylation stimulated by PDGF-AB, inhibited activation of mitogen-activated protein kinase (ERK) kinases (MEK1/2) and ERK1/2, and abrogated transcription factor AP-1 DNA-binding activity. Conclusions —Suramin inhibited SMC migration and proliferation in vivo and in vitro by blocking PDGF-initiated PDGF receptor and MAPK-AP-1 signaling. These findings indicate that locally applied suramin is effective in a mouse model of venous bypass graft arteriosclerosis.
Utility of the Hull airways reflux questionnaire in the assessment of patients in the acute admissions unit
Authors: Alyn Morice, Joanne Spriggs, Amanda Bell
Journal: European Respiratory Journal (2011)

Airway reflux and aspiration are thought to be common precipitants of acute exacerbations of COPD. A validated instrument, the Hull Airway Reflux Questionnaire (HARQ) has been developed to assess symptoms associated with airway reflux. The Acute Respiratory Assessment Service team are asked to review all respiratory admissions to the Acute Assessment Unit based in Hull Royal Infirmary. 55 patients, 22 male, mean age 67 were assessed over the winter of 2010/11. The admitting physician9s diagnosis was an acute exacerbation of COPD in 72% of patients, with other diagnoses including acute asthma, reflux and aspiration and lower respiratory tract infection. Mean HARQ score was 28 (mean score for normal subjects 4, with an upper limit of normal of 13). Just over half of the subjects scored in excess of 30 on the questionnaire giving a very high likelihood of the exacerbation being associated with an episode of airway reflux. There was an average of 2.1 previous admissions in the last two years. Surprisingly, there was no strong correlation between the number of previous exacerbations and the HARQ score.  Airway reflux and aspiration, unlike the liquid acid reflux of heartburn, can present without obvious classic symptoms. The HARQ questionnaire enables the clinician to diagnose non acid gaseous reflux impacting on the airway leading to bronchospasm and shortness of breath. This study suggests that the majority of patients presenting with acute exacerbations of COPD are in fact suffering from aspiration events which have previously been overlooked.
Tumor cell-selective apoptosis induction through targeting of KV10.1 via bifunctional TRAIL antibody
Authors: Franziska Hartung, Walter Stühmer, Luis A Pardo
Journal: Molecular Cancer (2011)

Abstract Background The search for strategies to target ion channels for therapeutic applications has become of increasing interest. Especially, the potassium channel K V 10.1 (Ether-á-go-go) is attractive as target since this surface protein is virtually not detected in normal tissue outside the central nervous system, but is expressed in approximately 70% of tumors from different origins. Methods We designed a single-chain antibody against an extracellular region of K V 10.1 (scFv62) and fused it to the human soluble TRAIL. The K V 10.1-specific scFv62 antibody -TRAIL fusion protein was expressed in CHO-K1 cells, purified by chromatography and tested for biological activity. Results Prostate cancer cells, either positive or negative for K V 10.1 were treated with the purified construct. After sensitization with cytotoxic drugs, scFv62-TRAIL induced apoptosis only in K V 10.1-positive cancer cells, but not in non-tumor cells, nor in tumor cells lacking K V 10.1 expression. In co-cultures with K V 10.1-positive cancer cells the fusion protein also induced apoptosis in bystander K V 10.1-negative cancer cells, while normal prostate epithelial cells were not affected when present as bystander. Conclusions K V 10.1 represents a novel therapeutic target for cancer. We could design a strategy that selectively kills tumor cells based on a K V 10.1-specific antibody.
Modulation of evoked contractions in rat arteries by ryanodine, thapsigargin, and cyclopiazonic acid.
Authors: H Shima, M P Blaustein
Journal: Circulation Research (1992)

The contribution of sarcoplasmic reticulum (SR) Ca2+ release to evoked tension in rat arterial rings was studied by comparing the effects of ryanodine (an SR Ca2+ channel opener) and thapsigargin and cyclopiazonic acid (CPA) (two Ca(2+)-ATPase inhibitors). Isometric tension was evoked by serotonin (5-HT), 30-50 mM external K+, and 10 mM caffeine in rings of aorta and a small (second-order) branch of the superior mesenteric artery (SMA). Resting tension was unaffected by 10 microM ryanodine or 1-5 microM thapsigargin, but 20 microM CPA raised resting tension in aortic rings and evoked spontaneous contractions in some SMA rings. Ryanodine (10 microM) or 1-5 microM thapsigargin partially depleted the SR Ca2+ stores (indicated by reduced caffeine-evoked contractions) and attenuated 5-HT- and high K(+)-evoked contractions in aortic rings but augmented 5-HT- and high K(+)-evoked contractions in SMA. Caffeine completely emptied the SR Ca2+ stores in the presence of ryanodine but not thapsigargin in both the aorta and SMA; thus, thapsigargin may selectively affect one component of a heterogeneous SR. When the aortic Ca2+ stores were empty (i.e., caffeine contractions were abolished), the 5-HT- and high K(+)-evoked contractions in the aorta were also augmented. CPA rapidly emptied the SR Ca2+ stores in both the aorta and SMA. CPA augmented the 5-HT-evoked contractions in the SMA and in five of nine aortic rings but attenuated evoked contractions in the remaining aortic rings. The attenuation or abolition of the caffeine contractions implies that ryanodine, thapsigargin, and CPA all deplete the SR Ca2+ stores. The attenuated responses to 5-HT and high K+ observed when the aortic SR Ca2+ stores were only partially depleted are consistent with the idea that evoked SR Ca2+ release is a large component of the Ca2+ transient in the aorta. The augmentation of 5-HT- and high K(+P)-evoked responses after partial (SMA) or complete (aorta) depletion of the SR Ca2+ stores suggests that evoked release of SR Ca2+ normally regulates Ca2+ entry by negative feedback and/or that the SR normally buffers the evoked rise in cytosolic Ca2+.
The Fine Specificity and Cytokine Profile of T-Helper Cells Responsive to the α3 Chain of Type IV Collagen in Goodpasture’s Disease
Authors: Lindsay S. Cairns, Richard G. Phelps, Laura Bowie, Andrew M. Hall, Walaa W.M. Saweirs, Andrew J. Rees, Robert N. Barker
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Goodpasture’s disease is a severe nephritis characterized by autoantibodies to the α3 chain of type IV collagen, α3(IV)NC1, in the glomerular basement membrane. The disease is very strongly associated with HLA-DR15, the affinities of α3(IV)NC1 peptides for DR15 are known, and elution experiments have identified major naturally processed sequences. Here, the fine specificity and cytokine profile of α3(IV)NC1-reactive T cells from patients with Goodpasture’s disease is defined. Peripheral blood mononuclear cells from patients at diagnosis proliferated in response to significantly more peptides (χ 2 = 8.6, P = 0.004) from a panel spanning the sequence of α3(IV)NC1 than did those from control DR15-positive donors and were highly focused ( P = 0.0002, binomial distribution) on two peptides, α3 71–90 and α3 131–150 . Some peptides induced interferon-γ, but none induced IL-4. Resolution of disease was accompanied by a striking deviation of the responses from proliferation to secretion of the T-regulatory cytokine IL-10, and addition of neutralizing antibody confirmed that such IL-10 production was suppressive. The affinity of the peptides for DR15 molecules was positively correlated (χ 2 = 14.6, P = 0.00067) with the ability to elicit proliferation. However, unlike foreign antigens, this hierarchy is not due to responses against the major naturally processed peptides, which rarely stimulated proliferation and which have only intermediate affinity for DR15 molecules. It is inferred that the helper response to α3(IV)NC1 in Goodpasture’s disease is dominated by epitopes that are normally inefficiently presented because of processing constraints. E-mail: r.n.barker@abdn.ac.uk
Atypical Subunit Composition of the Chlorophycean Mitochondrial F1FO-ATP Synthase and Role of Asa7 Protein in Stability and Oligomycin Resistance of the Enzyme
Authors: M. Lapaille, A. Escobar-Ramirez, H. Degand, D. Baurain, E. Rodriguez-Salinas, N. Coosemans, M. Boutry, D. Gonzalez-Halphen, C. Remacle, P. Cardol
Journal: Molecular Biology and Evolution (2010)

In yeast, mammals, and land plants, mitochondrial F1FO-ATP synthase (complex V) is a remarkable enzymatic machinery that comprises about 15 conserved subunits. Peculiar among eukaryotes, complex V from Chlamydomonadales algae (order of chlorophycean class) has an atypical subunit composition of its peripheral stator and dimerization module, with nine subunits of unknown evolutionary origin (Asa subunits). In vitro, this enzyme exhibits an increased stability of its dimeric form, and in vivo, Chlamydomonas reinhardtii cells are insensitive to oligomycins, which are potent inhibitors of proton translocation through the FO moiety. In this work, we showed that the atypical features of the Chlamydomonadales complex V enzyme are shared by the other chlorophycean orders. By biochemical and in silico analyses, we detected several atypical Asa subunits in Scenedesmus obliquus (Sphaeropleales) and Chlorococcum ellipsoideum (Chlorococcales). In contrast, complex V has a canonical subunit composition in other classes of Chlorophytes (Trebouxiophyceae, Prasinophyceae, and Ulvophyceae) as well as in Streptophytes (land plants), and in Rhodophytes (red algae). Growth, respiration, and ATP levels in Chlorophyceae were also barely affected by oligomycin concentrations that affect representatives of the other classes of Chlorophytes. We finally studied the function of the Asa7 atypical subunit by using RNA interference in C. reinhardtii. Although the loss of Asa7 subunit has no impact on cell bioenergetics or mitochondrial structures, it destabilizes in vitro the enzyme dimeric form and renders growth, respiration, and ATP level sensitive to oligomycins. Altogether, our results suggest that the loss of canonical components of the complex V stator happened at the root of chlorophycean lineage and was accompanied by the recruitment of novel polypeptides. Such a massive modification of complex V stator features might have conferred novel properties, including the stabilization of the enzyme dimeric form and the shielding of the proton channel. In these respects, we discuss an evolutionary scenario for F1FO-ATP synthase in the whole green lineage (i.e., Chlorophyta and Streptophyta).
Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes
Authors: David H. Munn, Madhav D. Sharma, Deyan Hou, Babak Baban, Jeffrey R. Lee, Scott J. Antonia, Jane L. Messina, Phillip Chandler, Pandelakis A. Koni, Andrew L. Mellor
Journal: Journal of Clinical Investigation (2004)

One mechanism contributing to immunologic unresponsiveness toward tumors may be presentation of tumor antigens by tolerogenic host APCs. We show that mouse tumor-draining LNs (TDLNs) contained a subset of plasmacytoid DCs (pDCs) that constitutively expressed immunosuppressive levels of the enzyme indoleamine 2,3-dioxygenase (IDO). Despite comprising only 0.5% of LN cells, these pDCs in vitro potently suppressed T cell responses to antigens presented by the pDCs themselves and also, in a dominant fashion, suppressed T cell responses to third-party antigens presented by nonsuppressive APCs. Adoptive transfer of DCs from TDLNs into naive hosts created profound local T cell anergy, specifically toward antigens expressed by the transferred DCs. Anergy was prevented by targeted disruption of the IDO gene in the DCs or by administration of the IDO inhibitor drug 1-methyl-D-tryptophan to recipient mice. Within the population of pDCs, the majority of the functional IDO-mediated suppressor activity segregated with a novel subset of pDCs coexpressing the B-lineage marker CD19. We hypothesize that IDO-mediated suppression by pDCs in TDLNs creates a local microenvironment that is potently suppressive of host antitumor T cell responses.
Motor unit regulation of mammalian pharyngeal dilator muscle activity.
Authors: E van Lunteren, T E Dick
Journal: Journal of Clinical Investigation (1989)

The present study examined the cellular regulation of one of the pharyngeal dilator muscles, the geniohyoid, by assessing its motor unit (MU) behavior in anesthetized cats. During spontaneous breathing, MU that (a) were active during inspiration only (I-MU) and (b) were active during both inspiration and expiration (I/E-MU) were identified. I-MU had a later inspiratory onset time and a shorter duration of inspiratory firing than did I/E-MU (P less than 0.002 and P less than 0.0001, respectively). I-MU were usually quiescent whereas I/E-MU were usually active during the last 20% of inspiration. I/E-MU fired more rapidly (P less than 0.00001) and for relatively longer periods of time (P less than 0.00001) during inspiration than during expiration. End-expiratory airway occlusion (preventing lung expansion during inspiration) augmented the inspiratory activity of both I-MU and I/E-MU. Conversely, end-expiratory airway occlusion reduced the absolute and relative firing durations (P less than 0.002 and P less than 0.00002, respectively) and the firing frequency (P less than 0.001) of I/E-MU activity during expiration. These results indicate that (a) the complex pattern of pharyngeal dilator muscle activity is due to the integrated activity of a heterogeneous group of MU, (b) changes in the degree to which pharyngeal dilator muscles are active result from combinations of MU recruitment/decruitment and modulations of the frequency and duration of MU firing, and (c) gating of lung-volume afferent information occurs during the respiratory cycle.
Spreading of tuberculosis with extensive drug resistant MBTin Northwest region of Russia
Authors: Goar Balasanjantc, Vladimir Galkin, Elena Torkayuk, Nataliya Isaeva
Journal: European Respiratory Journal (2014)

Introduction:WHO has defined extensive drug resistance (XDR) of Mycobacterium tuberculosis (MBT) as simultaneous resistance to isoniazid, rifampicin, fluoroquinolones and to one of injectable antibiotics - kanamycin, amikacin or c capreomycin.  Aims: to study structure of extensive drug resistant tuberculosis (XDR-TB) spreading in Northwest region of Russia  Methods: the results of 8070 drug sensitivity tests (DST) of from patients with first detected TB before treatment were collected from 11 territories of Northwest of Russia in period 2010-2012. Culture-based DST was done to more than 90 % (90.2% - 98.4%) of culture positive patients9 sputum samples. Drug resistance of MBT to essential and second-line antituberculous drugs was determined using phenotypic DST as absolute concentration method and MGIT 960 TB System.  Results: for the period 2010-2012 there were 99 first detected XDR-TB patients that made annually 1.4 %, 0.9 % and 1.2 % from all culture positive cases examined by DST. All XDR-TB patients had also resistance to essential drugs -streptomycin and ethambutol. XDR cases with resistance to fluoroquinolones and to one of injectable antibiotics have been identified in 64 patients specimens (64.6 %). At one third of cases resistance to other reserve drugs was identified, more often there were prothionamide-resistant strains (23 - 25.3 %). Last two years single cases with resistance to cycloserine (2 cases) or para-aminosalicylic acid (6 cases) were fixed. 4 patients had total drug resistance of MBT.  Conclusion: spreading of XDR-TB becomes serious challenge and renders significant negative influence on an epidemic situation in Northwest region of Russia.
Application of four molecular typing methods for analysis of Mycobacterium fortuitum group strains causing post-mammaplasty infections
Authors: J.L.M. Sampaio, E. Chimara, L. Ferrazoli, M.A. da Silva Telles, V.M.F. Del Guercio, Z.V.N. Jericó, K. Miyashiro, C.M.C.B. Fortaleza, M.C. Padoveze, S.C. Leão
Journal: Clinical Microbiology and Infection (2006)
Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial
Authors: Clemens von Birgelen, Hanim Sen, Ming Kai Lam, Peter W Danse, Gillian A J Jessurun, Raymond W M Hautvast, Gert K van Houwelingen, Alexander R Schramm, R Melvyn Tjon Joe Gin, Johannes W Louwerenburg, Frits H A F de Man, Martin G Stoel, Marije M Löwik, Gerard C M Linssen, Salah A M Saïd, Mark B Nienhuis, Patrick M J Verhorst, Mounir W Z Basalus, Carine J M Doggen, Kenneth Tandjung
Journal: The Lancet (2013)