tbuckley/cabot-search huggingface dataset:
THE EFFECTS ON BIOLOGICAL MATERIALS OF FREEZING AND DRYING BY VACUUM SUBLIMATION
Authors: Donald Greiff, Herman Blumenthal, Masahiro Chiga, Henry Pinkerton
Journal: The Journal of Experimental Medicine (1954)

The infectivity titre of influenza virus-infected allantoic fluid was determined after a variety of procedures involving cyclic slow freezing and thawing, freezing at various rates with subsequent storage at different temperatures freezing at various rates with subsequent dehydration at various temperatures, and different degrees of dehydration. All these factors were found to influence the survival rate of the virus particles. Five freeze-thaw cycles resulted in a fall in titre from 10(-8.6) to 10(-0.8) cycles 2, 3, and 4 causing much greater losses than cycles 1 and 5. Rapid cooling to -40 degrees C. or slow cooling to -80 or 190 degrees C. did not cause significant titre loss, but rapid cooling to temperatures above -40 degrees or slow cooling to temperatures above -80 degrees C. caused definite titre loss. Loss of titre on storage occurred only at temperatures above -40deg;C. The effect of lyophilization depends both on the preliminary treatment and on the dehydration temperature. Better conservation of titre was obtained after preliminary cooling to -190 or -80 degrees C. than after preliminary cooling to higher temperatures. The most effective sublimation temperatures were 0 and -80 degrees .; the least effective was +20 degrees C. Titre losses in suspensions sublimated at -10, -30, and -60 degrees C. were in general intermediate. No loss in titre occurred after preliminary cooling to -80 or -190 degrees C. and subsequent dehydration at -80 or 0 degrees C. The degree of dehydration definitely affects the survival of virus on storage at 0 degrees C., but sublimation for 4 hours at 0 degrees C. gave complete protection against titre loss on storage at this temperature. Possible explanations of the observations made are suggested, based on known physiochemical phenomena such as supercooling, vitrification, variations in size and shape of ice crystals with different freezing speeds, differential enzyme inactivation, changes in salt concentration, and changes in energy levels.
Smad7 Transgene Attenuates Peritoneal Fibrosis in Uremic Rats Treated with Peritoneal Dialysis
Authors: Hong Guo, Joseph C.K. Leung, Man Fai Lam, Loretta Y.Y. Chan, Anita W.L. Tsang, Hui Yao Lan, Kar Neng Lai
Journal: Journal of the American Society of Nephrology (2007)

Transforming growth factor beta (TGF-beta) plays a critical role in the pathogenesis of the peritoneal fibrosis that complicates long-term peritoneal dialysis (PD). We studied the TGF-beta/Smad signaling pathway in peritoneal fibrosis induced in uremic rats treated with PD and explored the therapeutic potential of Smad7 to prevent fibrogenesis. After subtotal nephrectomy, uremic rats were treated with peritoneal dialysis using 4.25% dextrose-containing fluid. The peritoneum of uremic rats treated with PD demonstrated fibrosis, increased TGF-beta expression, increased Smad2/3 activation, decreased Smad7 expression, and increased expression of fibrogenic and angiogenic factors. In addition, peritoneal function was impaired and its structure was altered, including a thickened submesothelial layer. In rats transfected with a Smad7 transgene using an ultrasound-microbubble-mediated system, peritoneal fibrosis was attenuated, peritoneal function was improved, and Smad2/3 activation was inhibited. We suggest that administration of Smad7 inhibits peritoneal fibrogenesis in uremic rats treated with PD by correcting the imbalance between downregulated Smad7 and activated Smad2/3. Blockade of the TGF-beta/Smad signaling pathway may represent a novel therapeutic approach to prevent peritoneal fibrosis in patients treated with PD.
Efficacy and safety analysis according to histology for S-1 in combination with carboplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer: updated results of the West Japan Oncology Group LETS study
Authors: H. Yoshioka, I. Okamoto, S. Morita, M. Ando, K. Takeda, T. Seto, N. Yamamoto, H. Saka, S. Atagi, T. Hirashima, S. Kudoh, M. Satouchi, N. Ikeda, Y. Iwamoto, T. Sawa, Y. Nakanishi, K. Nakagawa
Journal: Annals of Oncology (2013)
Protein Kinase A–Mediated Phosphorylation of cMyBP-C Increases Proximity of Myosin Heads to Actin in Resting Myocardium
Authors: Brett A. Colson, Tanya Bekyarova, Matthew R. Locher, Daniel P. Fitzsimons, Thomas C. Irving, Richard L. Moss
Journal: Circulation Research (2008)

Protein kinase A-mediated (PKA) phosphorylation of cardiac myosin binding protein C (cMyBP-C) accelerates the kinetics of cross-bridge cycling and may relieve the tether-like constraint of myosin heads imposed by cMyBP-C. We favor a mechanism in which cMyBP-C modulates cross-bridge cycling kinetics by regulating the proximity and interaction of myosin and actin. To test this idea, we used synchrotron low-angle x-ray diffraction to measure interthick filament lattice spacing and the equatorial intensity ratio, I(11)/I(10), in skinned trabeculae isolated from wild-type and cMyBP-C null (cMyBP-C(-/-)) mice. In wild-type myocardium, PKA treatment appeared to result in radial or azimuthal displacement of cross-bridges away from the thick filaments as indicated by an increase (approximately 50%) in I(11)/I(10) (0.22+/-0.03 versus 0.33+/-0.03). Conversely, PKA treatment did not affect cross-bridge disposition in mice lacking cMyBP-C, because there was no difference in I(11)/I(10) between untreated and PKA-treated cMyBP-C(-/-) myocardium (0.40+/-0.06 versus 0.42+/-0.05). Although lattice spacing did not change after treatment in wild-type (45.68+/-0.84 nm versus 45.64+/-0.64 nm), treatment of cMyBP-C(-/-) myocardium increased lattice spacing (46.80+/-0.92 nm versus 49.61+/-0.59 nm). This result is consistent with the idea that the myofilament lattice expands after PKA phosphorylation of cardiac troponin I, and when present, cMyBP-C, may stabilize the lattice. These data support our hypothesis that tethering of cross-bridges by cMyBP-C is relieved by phosphorylation of PKA sites in cMyBP-C, thereby increasing the proximity of cross-bridges to actin and increasing the probability of interaction with actin on contraction.
Smoking status and long term clinical outcome in patients with pulmonary Langerhans cell histiocytosis
Authors: Chikatoshi Sugimoto, Toru Arai, Masanori Kitaichi, Masanori Akira, Aya Hirooka, Shojiro Minomo, Seiji Hayashi, Yoshikazu Inoue
Journal: European Respiratory Journal (2013)

Background and aim:  Pulmonary Langerhans cell histiocytosis (PLCH) is a rare lung disease, which occurs predominantly in adult cigarette smokers. However, correlation between smoking status and long-term clinical outcome has not been well known.   Methods:  To clarify the smoking effects, we retrospectively analyzed clinical data (pulmonary function, CT, clinical data) from 15 (7 female, 8 male, median age 28 years old, range 16-63) patients with PLCH, who were pathologically diagnosed in our institution.   Results:  All 15 patients were smokers (median 19.5 pack-year, range, 1-49.5). The median follow-up period was 2.2 (range, 0.5 to 25.5) years. The median %FEV 1  was 86.8% (range 40.7-117.0), and the median FEV 1 /FVC ratio was 0.82 (range, 0.59 to 0.97). 5 cases were followed up for more than 10 years. 3 cases repeated smoking and smoking cessation. Only 1 case kept smoking cessation. 1 case continued to smoking. In all cases, cystic opacities were observed in lung CT at the last visit, and FEV 1 /FVC ratio at last visit was deteriorated as compared with FEV 1 /FVC ratio at diagnosis. In 1 case, %FEV 1  was increased, and nodular opacities were disappeared without smoking cessation. 1 case died of lung cancer with smoking cessation and was performed autopsy. Traction emphysema without centrilobular emphysema was extensively observed in his histology. FEV 1 /FVC ratio was deteriorated in all long-term followed 5 patients regardless of smoking.   Conclusion:  We conclude that smoking cessation does not always result in improvement of pulmonary function and HRCT finding in PLCH.  This study was supported by the grants from National Hospital Organization, and the ministry of Health, Labour, and Welfare.
Transforming growth factor 1 gene (HSTGFB1) nucleotide T869C (codon 10) polymorphism is not associated with prevalence or severity of rheumatoid arthritis in a Caucasian population
Authors: V Pokorny
Journal: Annals of the Rheumatic Diseases (2003)

In a recent report in the Annals Sugiura and colleagues found an association between rheumatoid arthritis (RA) and a single nucleotide polymorphism (SNP) of HSTGFB1 at nucleotide (nt) +869 (T869C; nt position relative to GenBank accession X05839), a coding SNP producing a Leu→ Pro substitution in codon 10.1 The CC genotype was found in 29/155 (19%) central Japanese patients with RA compared with 33/110 (30%) controls and this was significant when the CT and TT genotypes were pooled. Codon 10 is in the signalling peptide region and the Pro (869C) allele has been associated with higher transforming growth factor β1 (TGFβ1) production. TGFβ1 is present in the synovial tissue of patients with RA, and in addition to its profibrotic activities has regulatory effects on cells important in the pathogenesis of RA, including lymphocytes, dendritic cells, macrophages, chondrocytes, and osteoblasts.2–5 Administration of TGFβ suppresses collagen induced arthritis, whereas antibodies to TGFβ exaggerate the process.6 Crilly and colleagues reported an increase in the high producing codon 10 Leu (nt869T) in patients with systemic sclerosis.7 This polymorphism has also been associated with osteoporosis and with osteophytosis.8,9

To explore whether this polymorphism is associated with the prevalence and/or severity of RA in white …
Torcetrapib Does Not Reduce Atherosclerosis Beyond Atorvastatin and Induces More Proinflammatory Lesions Than Atorvastatin
Authors: Willeke de Haan, Jitske de Vries-van der Weij, José W.A. van der Hoorn, Thomas Gautier, Caroline C. van der Hoogt, Marit Westerterp, Johannes A. Romijn, J. Wouter Jukema, Louis M. Havekes, Hans M.G. Princen, Patrick C.N. Rensen
Journal: Circulation (2008)

Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even increased cardiovascular death in the recent Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events trial. Therefore, we evaluated the antiatherogenic potential and adverse effects of torcetrapib in humanized APOE*3-Leiden.CETP (E3L.CETP) mice.E3L.CETP mice were fed a cholesterol-rich diet without drugs or with torcetrapib (12 mg x kg(-1) x d(-1)), atorvastatin (2.8 mg x kg(-1) x d(-1)), or both for 14 weeks. Torcetrapib decreased CETP activity in both the absence and presence of atorvastatin (-74% and -73%, respectively; P<0.001). Torcetrapib decreased plasma cholesterol (-20%; P<0.01), albeit to a lesser extent than atorvastatin (-42%; P<0.001) or the combination of torcetrapib and atorvastatin (-40%; P<0.001). Torcetrapib increased high-density lipoprotein cholesterol in the absence (30%) and presence (34%) of atorvastatin. Torcetrapib and atorvastatin alone reduced atherosclerotic lesion size (-43% and -46%; P<0.05), but combination therapy did not reduce atherosclerosis compared with atorvastatin alone. Remarkably, compared with atorvastatin, torcetrapib enhanced monocyte recruitment and expression of monocyte chemoattractant protein-1 and resulted in lesions of a more inflammatory phenotype, as reflected by an increased macrophage content and reduced collagen content.CETP inhibition by torcetrapib per se reduces atherosclerotic lesion size but does not enhance the antiatherogenic potential of atorvastatin. However, compared with atorvastatin, torcetrapib introduces lesions of a less stable phenotype.
Zerumbone Enhances TRAIL-Induced Apoptosis through the Induction of Death Receptors in Human Colon Cancer Cells: Evidence for an Essential Role of Reactive Oxygen Species
Authors: Supachai Yodkeeree, Bokyung Sung, Pornngarm Limtrakul, Bharat B. Aggarwal
Journal: Cancer Research (2009)

Identification of the active component and mechanisms of action of traditional medicines is highly desirable. We investigated whether zerumbone, a sesquiterpene from tropical ginger, can enhance the anticancer effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found that zerumbone potentiated TRAIL-induced apoptosis in human HCT116 colon cancer cells and that this correlated with the up-regulation of TRAIL death receptor (DR) 4 and DR5. Induction of DRs occurred at the transcriptional level, and this induction was not cell-type specific, as its expression was also up-regulated in prostate, kidney, breast, and pancreatic cancer cell lines. Deletion of DR5 or DR4 by small interfering RNA significantly reduced the apoptosis induced by TRAIL and zerumbone. In addition to up-regulating DRs, zerumbone also significantly down-regulated the expression of cFLIP but not that of other antiapoptotic proteins. The induction of both DRs by zerumbone was abolished by glutathione and N-acetylcysteine (NAC), and this correlated with decreased TRAIL-induced apoptosis, suggesting a critical role of reactive oxygen species. Inhibition of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase but not of Jun NH(2)-terminal kinase abolished the effect of zerumbone on DR induction. Zerumbone also induced the p53 tumor suppressor gene but was found to be optional for DR induction or for enhancement of TRAIL-induced apoptosis. Both bax and p21, however, were required for zerumbone to stimulate TRAIL-induced apoptosis. Overall, our results show that zerumbone can potentiate TRAIL-induced apoptosis through the reactive oxygen species-mediated activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase leading to DR4 and DR5 induction and resulting in enhancement of the anticancer effects of TRAIL.
Brain Morphometric Abnormalities in Geriatric Depression: Long-Term Neurobiological Effects of Illness Duration
Authors: Sandra Bell-McGinty, Meryl A. Butters, Carolyn Cidis Meltzer, Phil J. Greer, Charles F. Reynolds, James T. Becker
Journal: American Journal of Psychiatry (2002)

The authors' goal was to compare regional brain volumes in depressed elderly subjects with those of nondepressed elderly subjects by using voxel-based morphometry.They used statistical parametric mapping to analyze magnetic resonance imaging scans from 30 depressed patients 59 to 78 years old and 47 nondepressed comparison subjects 55 to 81 years old.Depressed patients had smaller right hippocampal volume than comparison subjects. The volume of the hippocampal-entorhinal cortex was inversely associated with the number of years since the first lifetime episode of depression.These data provide further evidence of structural brain abnormalities in geriatric depression, particularly in patients with a longer course of illness.
A phase II study to evaluate the combination of fludarabine, mitoxantrone and dexamethasone (FMD) in patients with follicular lymphoma
Authors: C.R. Crawley, J.M. Foran, R.K. Gupta, A.Z.S. Rohatiner, K. Summers, J. Matthews, I.N.M. Micallef, J.A. Radford, S.A. Johnson, P.W. Johnson, J.W. Sweetenham, T.A. Lister
Journal: Annals of Oncology (2000)
Antibacterial effect of human Vγ2Vδ2 T cells in vivo
Authors: Lisheng Wang, Arati Kamath, Hiranmoy Das, Lin Li, Jack F. Bukowski
Journal: Journal of Clinical Investigation (2001)

Vγ2Vδ2 cells, a class of T cells found only in primates, are reactive to nonpeptide organophosphate and alkylamine antigens secreted by bacteria and parasites. These cells make up 2-5% percent of human peripheral blood T cells but expand to make up 8–60% of peripheral blood T cells during bacterial and parasitic infections. We show here, using a chimeric severe combined immunodeficiency (SCID) mouse (hu-SCID) model, that human Vγ2Vδ2 T cells mediate resistance to extracellular gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli and Morganella morganii) bacteria, as assessed by survival, body weight, bacterial loads, and histopathology. Surprisingly, this bacterial resistance was evident 1 day after infection, and bacteria were cleared well before γδ T cell expansion was detected 6 days after infection. Decreased resistance in Vδ2 T cell–depleted hu-SCID mice correlated with decreased serum IFN-γ titers. Intravenous treatment of infected, reconstituted hu-SCID mice with pamidronate, a human Vγ2Vδ2 T cell–specific aminobisphosphonate antigen, markedly increased the in vivo antibacterial effect of Vγ2Vδ2 T cells. Therefore, this large pool of antigen-specific, yet immediately reactive memory human Vγ2Vδ2 T cells is likely to be an important mediator of resistance against extracellular bacterial infection and may bridge the gap between innate and acquired immunity.
Inhibition of Growth of Human Lung Adenocarcinoma Cell Lines by Anti-Transforming Growth Factor- Monoclonal Antibody
Authors: K.-i. Imanishi, K. Yamaguchi, M. Kuranami, E. Kyo, T. Hozumi, K. Abe
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Inhibition of Growth of Human Lung Adenocarcinoma Cell Lines by Anti-Transforming Growth Factor-α Monoclonal Antibody Get access Koh-ichi Imanishi, Koh-ichi Imanishi Growth Factor Division, National Cancer Center Research InstituteTsukiji 5–1–1, Chuo-ku, Tokyo 104, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Ken Yamaguchi, Ken Yamaguchi Growth Factor Division, National Cancer Center Research InstituteTsukiji 5–1–1, Chuo-ku, Tokyo 104, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Masaru Kuranami, Masaru Kuranami Growth Factor Division, National Cancer Center Research InstituteTsukiji 5–1–1, Chuo-ku, Tokyo 104, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Eikai Kyo, Eikai Kyo Institute for Biotechnology Research of Wakunaga Pharmaceutical Co., LtdHiroshima, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Toyoharu Hozumi, Toyoharu Hozumi Institute for Biotechnology Research of Wakunaga Pharmaceutical Co., LtdHiroshima, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Kaoru Abe Kaoru Abe Department of Medicine, National Cancer Center HospitalTokyo Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 3, 1 February 1989, Pages 220–223, https://doi.org/10.1093/jnci/81.3.220 Published: 01 February 1989 Article history Received: 31 October 1988 Accepted: 09 November 1988 Published: 01 February 1989
“Inside-Out” Signaling of Sphingosine-1-Phosphate: Therapeutic Targets
Authors: Kazuaki Takabe, Steven W. Paugh, Sheldon Milstien, Sarah Spiegel
Journal: Pharmacological Reviews (2008)

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cellular processes including proliferation, survival, and migration, as well as angiogenesis and allergic responses. S1P levels inside cells are tightly regulated by the balance between its synthesis by sphingosine kinases and degradation. S1P is interconvertible with ceramide, which is a critical mediator of apoptosis. It has been postulated that the ratio between S1P and ceramide determines cell fate. Activation of sphingosine kinase by a variety of agonists increases intracellular S1P, which in turn can function intracellularly as a second messenger or be secreted out of the cell and act extracellularly by binding to and signaling through S1P receptors in autocrine and/or paracrine manners. Recent studies suggest that this "inside-out" signaling by S1P may play a role in many human diseases, including cancer, atherosclerosis, inflammation, and autoimmune disorders such as multiple sclerosis. In this review we summarize metabolism of S1P, mechanisms of sphingosine kinase activation, and S1P receptors and their downstream signaling pathways and examine relationships to multiple disease processes. In particular, we describe recent preclinical and clinical trials of therapies targeting S1P signaling, including 2-amino-2-propane-1,3-diol hydrochloride (FTY720, fingolimod), S1P receptor agonists, sphingosine kinase inhibitors, and anti-S1P monoclonal antibody.
Potassium Channel Subunit Remodeling in Rabbits Exposed to Long-Term Bradycardia or Tachycardia
Authors: Yukiomi Tsuji, Stephen Zicha, Xiao-Yan Qi, Itsuo Kodama, Stanley Nattel
Journal: Circulation (2006)

Sustained heart rate abnormalities produce electrical remodeling and susceptibility to arrhythmia. Uncontrolled tachycardia produces heart failure and ventricular tachyarrhythmia susceptibility, whereas bradycardia promotes spontaneous torsade de pointes (TdP). This study compared arrhythmic phenotypes and molecular electrophysiological remodeling produced by tachycardia versus bradycardia in rabbits.We evaluated mRNA and protein expression of subunits underlying rapid (IKr) and slow (IKs) delayed-rectifier and transient-outward K+ currents in ventricular tissues from sinus rhythm control rabbits and rabbits with AV block submitted to 3-week ventricular pacing either at 60 to 90 bpm (bradypaced) or at 350 to 370 bpm (tachypaced). QT intervals at matched ventricular pacing rates were longer in bradypaced than tachypaced rabbits (eg, by approximately 50% at 60 bpm; P<0.01). KvLQT1 and minK mRNA and protein levels were downregulated in both bradypaced and tachypaced rabbits, whereas ERG was significantly downregulated in bradypaced rabbits only. Kv4.3 and Kv1.4 were downregulated by tachypacing only. Patch-clamp experiments showed that IKs was reduced in both but IKr was decreased in bradypaced rabbits only. Continuous monitoring revealed spontaneous TdP in 75% of bradypaced but only isolated ventricular ectopy in tachypaced rabbits. Administration of dofetilide (0.02 mg/kg) to mimic IKr downregulation produced ultimately lethal TdP in all tachypaced rabbits.Sustained tachycardia and bradycardia downregulate IKs subunits, but bradycardia also suppresses ERG/IKr, causing prominent repolarization delays and spontaneous TdP. Susceptibility of tachycardia/heart failure rabbits to malignant tachyarrhythmias is induced by exposure to IKr blockers. These results point to a crucial role for delayed-rectifier subunit remodeling in TdP susceptibility associated with rate-related cardiac remodeling.
Remitting distal lower extremity swelling with pitting oedema in acute sarcoidosis
Authors: F. CANTINI, L. NICCOLI, I. OLIVIERI, L. BAROZZI, P. PAVLICA, A. BOZZA, P. L. MACCHIONI, A. PADULA, C. SALVARANI
Journal: Annals of the Rheumatic Diseases (1997)

Remitting distal extremity swelling with pitting oedema is a clinical manifestation that may be observed in different rheumatic conditions such as RS3PE syndrome,1 polymyalgia rheumatica,2 late onset undifferentiated spondyloarthropathy,3 ankylosing spondylitis,4 psoriatic arthritis,5 and more rarely in other rheumatic disease.5 In RS3PE the swelling with pitting oedema predominantly involves the upper extremities symmetrically.1 This clinical finding may occur unilaterally in polymyalgia rheumatica and upper and lower limbs may be equally affected,2 whereas in seronegative spondyloarthropathies it has been described more frequently in lower extremities with asymmetric involvement.3 4 

The oedema is characterised by a rapid response to small doses of corticosteroids.

The pathogenesis of swelling with pitting oedema has not been completely defined, but the distribution along the tenosynovial membranes suggests that it probably results from tenosynovitis.5 

Sarcoidosis is a …