tbuckley/cabot-search huggingface dataset:
The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis
Authors: A Meyer, R Buhl, H Magnussen
Journal: European Respiratory Journal (1994)

Idiopathic pulmonary fibrosis (IPF) is characterized by an increased oxidant burden and by a deficiency of glutathione, a major antioxidant, in the lung epithelial lining fluid (ELF). Therefore, a rational therapeutic approach is to reverse the imbalance between oxidants and antioxidants in the lung by enhancing the antioxidant screen. With this background, the aim of our study was to evaluate oral N-acetylcysteine (NAC) as a strategy to augment lung glutathione levels in patients with IPF. Concentrations of total glutathione in bronchoalveolar lavage fluid (BALF) were quantified spectrophotometrically, before and following oral therapy with 3 x 600 mg NAC per day for 5 days, in 17 nonsmoking patients with biopsy-proven IPF. The volume of ELF recovered by BAL was determined using the urea method. Pretherapy, total glutathione levels in ELF in IPF patients were significantly less than normal (187 +/- 36 vs 368 +/- 60 microM), in contrast to levels in BALF (0.99 +/- 0.12 vs 1.18 +/- 0.19 microM). Following therapy with oral NAC, glutathione levels in BALF were 1.54 +/- 0.24 microM (a significant increase compared to pretherapy), whereas the increase in ELF levels (319 +/- 92 microM) did not reach significance. The therapy was well-tolerated, and all routine clinical and bronchoscopic parameters remained unchanged. It is thus feasible and safe to augment deficient lung glutathione levels in patients with IPF; thereby, potentially augmenting pulmonary antioxidant protection.
Tolerance of CD8+ T cells developing in parent--&amp;gt;F1 chimeras prepared with supralethal irradiation: step-wise induction of tolerance in the intrathymic and extrathymic environments.
Authors: H Kosaka, J Sprent
Journal: The Journal of Experimental Medicine (1993)

Tolerance of CD8+ cells was examined in parent--&amp;gt;F1 bone marrow chimeras (BMC) prepared with supralethal irradiation; host class I expression in the chimeras was limited to non-BM-derived cells. In terms of helper-independent proliferative responses in vitro and induction of graft-vs.-host disease on adoptive transfer, CD8+ cells from long-term chimeras showed profound tolerance to host antigens irrespective of whether the cells were prepared from the thymus or from spleen or lymph nodes. By limiting dilution analysis, cytotoxic T lymphocyte (CTL) precursors specific for host antigens were rare in the extrathymic lymphoid tissues. In the thymus, by contrast, host-specific CTL precursors were only slightly less frequent than in normal parental strain mice. These host-specific CD8+ cells survived when BMC thymocytes were transferred intravenously to a neutral environment, i.e., to donor strain mice. When transferred to further BMC hosts, however, most of the host-reactive cells disappeared. Collectively, the data suggest that tolerance of CD8+ cells in BMC hosts occurs in both the intrathymic and extrathymic environments. In the thymus, contact with host antigens on thymic epithelial cells deletes CD8+ cells controlling helper-independent proliferative responses and in vivo effector functions but spares typical helper-dependent CTL precursors. After export from the thymus, most of the CTL precursors are eliminated after contacting host antigens on stromal cells in the extrathymic environment.
Growth of colorectal polyps: redetection and evaluation of unresected polyps for a period of three years.
Authors: B Hofstad, M H Vatn, S N Andersen, H S Huitfeldt, T Rognum, S Larsen, M Osnes
Journal: Gut (1996)

BACKGROUND, AIMS, AND PATIENTS: In a prospective follow up and intervention study of colorectal polyps, leaving all polyps less than 10 mm in situ for three years, analysis of redetection rate, growth, and new polyp formation was carried out in 116 patients undergoing annual colonoscopy. The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo. RESULTS: Redetection rate varied from 75-90% for each year, and was highest in the rectum and sigmoid colon. There was no net change in size of all polyps in the placebo group, however, polyps less than 5 mm showed a tendency to net growth, and polyps 5-9 mm a tendency to net regression in size, both for adenomas and hyperplastic polyps. This pattern was verified by computerised image analysis. Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients, and the same was true for those with multiple adenomas (four to five) compared with those with a single adenoma. The new adenomas were significantly smaller and 71% were located in the right side of the colon. Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma. One patient developed an invasive colorectal carcinoma, which may be evolved from a previously overlooked polyp. Two polyps, showing intramucosal carcinoma after follow up for three years, were completely removed, as judged by endoscopy and histological examination. CONCLUSIONS: The results show that follow up of unresected colorectal polyps up to 9 mm is safe. The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations, but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice. The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer.
78 SUB-CLASSIFICATION OF CIRRHOSIS AND PREDICTION OF LIVER-RELATED EVENTS USING FIBROSCAN IN PATIENTS WITH HBV-RELATED CIRRHOSIS
Authors: S.U. Kim, H.J. Oh, Y.N. Park, J.Y. Park, D.Y. Kim, S.H. Ahn, C.Y. Chon, K.-H. Han
Journal: Journal of Hepatology (2012)
Randomised, controlled trial of efficacy of midwife-managed care
Authors: Deborah Tumbull, Ann Holmes, Noreen Shields, Helen Cheyne, Sara Twaddle, W Harper Gilmour, Mary McGinley, Margaret Reid, Irene Johnstone, Ian Geer, Gillian Mcllwaine, C Burnett Lunan
Journal: The Lancet (1996)
Evidence for increased aortic plasma membrane calcium transport caused by experimental atherosclerosis in rabbits.
Authors: S A Strickberger, L N Russek, R D Phair
Journal: Circulation Research (1988)

Several lines of evidence, including the reported ability of calcium channel blockers to prevent atherogenesis in cholesterol-fed rabbits, suggest that calcium mediates one or more of the pathologic changes in atherosclerosis. Moreover, it has long been known that calcium accumulates in atherosclerotic blood vessels. To test the hypothesis that a substantial fraction of this accumulated calcium is intracellular and to identify possible causes of this accumulation, calcium fluxes and contents were determined in aortic segments from cholesterol-fed rabbits and age-matched controls. A new method, based on 45Ca efflux experiments and computer-assisted kinetic analysis, was used to measure intracellular and extracellular calcium contents (nmol calcium/g wet wt tissue) and fluxes. Total intracellular calcium increased from 269 +/- 11.6 to 1,300 +/- 352 nmol/g in cholesterol-fed animals compared with controls (p less than 0.01). This change was sufficient to account for the observed increase in total tissue calcium from 4,190 +/- 211 to 5,240 +/- 477 nmol/g (p less than 0.05). Thus, the fraction of tissue calcium that is intracellular increased significantly from 0.065 +/- 0.006 to 0.223 +/- 0.048 (p less than 0.01) in experimental atherosclerosis. In addition, the data were quantitatively consistent with the hypothesis that these changes are brought about by a 4.8-fold increase in the plasma membrane calcium permeability of aortic smooth muscle cells. These results provide evidence that increased intracellular calcium is a possible mediator of cholesterol-induced atherogenesis.
Guidelines for the treatment of osteoarthritis
Authors: D E Furst
Journal: Annals of the Rheumatic Diseases (2002)

Guidelines for the treatment of osteoarthritisGuidelines for the treatment of osteoarthritis (OA) have several purposes, but a major one relates to its use by regulatory or medical insurance agencies that use it to help guide their response to requests for drugs to treat patients.Data have recently been published which record the efficacy of non-steroidal antiinflammatory drugs (NSAIDs) over paracetamol (acetaminophen) and report patients' preferences for NSAIDs rather than paracetamol in the treatment of OA. [1][2][3][4][5][6][7] Furthermore, inflammation is a common accompaniment of moderate to severe OA. [8][9][10] Therefore it would seem appropriate to consider the use of NSAIDs as the primary treatment in the group of patients with OA with moderate to severe pain or inflammation as part of their disease.The EULAR Guidelines state that paracetamol is the first line of treatment for all patients with OA, 11 despite the recent evidence that NSAIDs are more efficacious than paracetamol and that paracetamol is associated with more gastrointestinal toxicity than was previously thought. 12ould it not be more appropriate to suggest that patients who have moderate to severe pain and/or OA with inflammatory components be given NSAIDs as the first line of treatment, leaving paracetamol for symptomatic use in those patients with lesser degrees of pain or lack of overt inflammation?
T Cell Costimulation Molecules CD80/86 Inhibit Osteoclast Differentiation by Inducing the IDO/Tryptophan Pathway
Authors: Aline Bozec, Mario M. Zaiss, Rosebeth Kagwiria, Reinhard Voll, Manfred Rauh, Zhu Chen, Sandra Mueller-Schmucker, Richard A. Kroczek, Lucie Heinzerling, Muriel Moser, Andrew L. Mellor, Jean-Pierre David, Georg Schett
Journal: Science Translational Medicine (2014)

Costimulatory molecules CD80/CD86 suppress osteoclast differentiation by inducing indoleamine 2,3-dioxygenase.
THE B7 FAMILY REVISITED
Authors: Rebecca J. Greenwald, Gordon J. Freeman, Arlene H. Sharpe
Journal: Annual Review of Immunology (2005)

The discovery of new functions for the original B7 family members, together with the identification of additional B7 and CD28 family members, have revealed new ways in which the B7:CD28 family regulates T cell activation and tolerance. B7-1/B7-2:CD28 interactions not only promote initial T cell activation but also regulate self-tolerance by supporting CD4+CD25+ T regulatory cell homeostasis. CTLA-4 can exert its inhibitory effects in both B7-1/B7-2 dependent and independent fashions. B7-1 and B7-2 can signal bidirectionally by engaging CD28 and CTLA-4 on T cells and by delivering signals into B7-expressing cells. The five new B7 family members, ICOS ligand, PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H3, and B7-H4 (B7x/B7-S1) are expressed on professional antigen-presenting cells as well as on cells within nonlymphoid organs, providing new means for regulating T cell activation and tolerance in peripheral tissues. The new CD28 families members, ICOS, PD-1, and BTLA, are inducibly expressed on T cells, and they have important roles in regulating previously activated T cells. PD-1 and BTLA also are expressed on B cells and may have broader immunoregulatory functions. The ICOS:ICOSL pathway appears to be particularly important for stimulating effector T cell responses and T cell-dependent B cell responses, but it also has an important role in regulating T cell tolerance. In addition, the PD-1:PD-L1/PD-L2 pathway plays a critical role in regulating T cell activation and tolerance. In this review, we revisit the roles of the B7:CD28 family members in regulating immune responses, and we discuss their therapeutic potential.
Longitudinal analyses of chest radiographs from the European Carbon Black Respiratory Morbidity Study
Authors: M.J.A. van Tongeren, K. Gardiner, C.E. Rossiter, J. Beach, P. Harber, M.J. Harrington
Journal: European Respiratory Journal (2002)

High levels of exposure to carbon black have been linked with an increased prevalence of chest radiograph abnormalities. However, it is unclear to what extent current levels of exposure in the carbon black manufacturing industry are associated with new cases of and progression in small opacities. Longitudinal analyses were carried out on data from workers in the European carbon black manufacturing industry who provided three full-size chest radiographs sequentially between 1987–1995. All chest radiographs were independently read by three experienced readers according to the International Labour Organisation (ILO) classification. After exclusion of participants with previous lung diseases or injuries, females, unreadable chest radiographs and from factories with a low participation rate, data from 675 workers were available for the longitudinal analyses. An association was observed between cumulative carbon black exposure and new cases of chest radiograph abnormalities (ILO category ≥1/0) and progression in small opacities. These associations were mainly related to changes in chest radiographs from workers at one factory. A large percentage of workers with chest radiograph abnormalities reversed to normal chest films; however, after adjusting for other factors, this was not associated with levels of exposure to carbon black dust. In conclusion, the results show that exposure to carbon black is associated with increased risk of chest radiographic abnormalities, which may be reversible after reduction or cessation of exposure.
Langerhans Cell Histiocytosis Masquerading As Aneurysmal Bone Cyst
Authors: Chandra Krishnan
Journal: Journal of Clinical Oncology (2011)

Case ReportAn 8-year-old girl presented with a several-week history of a bump on her occiput.The bump was discovered after a minor trauma to the region resulting from a low-impact fall.No loss of consciousness or other localizing acute symptoms were reported.Magnetic resonance imaging (MRI) was performed because of increased pain and the persistent nature of the bump.T1-and T2-weighted images (Figs 1A, 1B) showed an expansile, destructive, and lytic mass located in the midline of the occipital bone.The lesion was notable for the presence of multiple fluid-fluid levels and layering hemorrhage that was best observed on the T2-weighted image (Fig 1B).The lesion measured 3.75 ϫ 2.45 ϫ 4.30 cm and exerted a mass effect on the sagittal sinus.No brain involvement was noted.On the basis of the classic radiographic features, the differential diagnosis favored an aneurysmal bone cyst (ABC).Other, less likely entities considered included telangiectatic osteosarcoma and metastatic tumor.The lesion was completely excised via craniotomy.Postoperatively, the patient encountered some poor wound healing and a bacterial infection of the surgical site.Ultimately, she recovered without additional undue complications.To date (6 months after surgery), there has been no evidence of recurrent disease or other systemic lesions.
Glucose Regulated Protein 78 Diminishes α-Synuclein Neurotoxicity in a Rat Model of Parkinson Disease
Authors: Marina S Gorbatyuk, Arseniy Shabashvili, Weijun Chen, Craig Meyers, Layla F Sullivan, Max Salganik, Jonathan H Lin, Alfred S Lewin, Nicholas Muzyczka, Oleg S Gorbatyuk
Journal: Molecular Therapy (2012)

Accumulation of human wild-type (wt) α-synuclein (α-syn) induces neurodegeneration in humans and in experimental rodent models of Parkinson disease (PD). It also leads to endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). We overexpressed glucose regulated protein 78, also known as BiP (GRP78/BiP), to test the hypothesis that this ER chaperone modulates the UPR, blocks apoptosis, and promotes the survival of nigral dopamine (DA) neurons in a rat model of PD induced by elevated level of human α-syn. We determined that α-syn activates ER stress mediators associated with pancreatic ER kinase-like ER kinase (PERK) and activating transcription factor-6 (ATF6) signaling pathways as well as proaoptotic CCAAT/-enhancer-binding protein homologous protein (CHOP) in nigral DA neurons. At the same time, overexpression of GRP78/BiP diminished α-syn neurotoxicity by down regulating ER stress mediators and the level of apoptosis, promoted survival of nigral tyrosine hydroxylase (TH) positive cells and resulted in higher levels of striatal DA, while eliminating amphetamine induced behavioral asymmetry. We also detected a complex between GRP78/BiP and α-syn that may contribute to prevention of the neurotoxicity caused by α-syn. Our data suggest that the molecular chaperone GRP78/BiP plays a neuroprotective role in α-syn-induced Parkinson-like neurodegeneration.
Ketorolac versus Acetaminophen or Ibuprofen in Controlling Postoperative Pain in Patients with Strabismus
Authors: Nancy A. Morrison, Michael X. Repka
Journal: Ophthalmology (1994)

Purpose: Ketorolac is a new, parenteral, nonsteroidal, anti-inflammatory agent.The authors compare the effectiveness of a single intravenous dose of ketorolac with a single oral dose of either acetaminophen or ibuprofen in controlling postoperative pain in patients with strabismus.Methods: A prospective, randomized, double-masked study was performed on 60 patients older than 12 years of age who were undergoing strabismus surgery.The patients were randomized into one of three single-dosage treatment groups: group 1 received oral acetaminophen (650 mg); group 2 received oral ibuprofen (600 mg); and group 3 received intravenous ketorolac (60 mg) intraoperatively and placebo capsules postoperatively.Pain and sedation levels were assessed at 2 and 5 hours after surgery by having the patient mark a standard 100-mm visual analog scale.Results: The ketorolac-treated patients had significantly less pain at both the 2and 5-hour intervals after surgery compared with either the acetaminophen or ibuprofen groups (P = 0.001).There was no difference in the level of sedation among any of the three treatment groups. Conclusion:Intravenous ketorolac given at the conclusion of surgery was more effective than either oral acetaminophen or oral ibuprofen given 30 to 45 minutes after strabismus surgery in controlling postoperative pain.Pain relief was achieved earlier by intravenous delivery than by oral agents.Greater pain relief with ketorolac was sustained 5 hours after surgery.This facilitates suture adjustment and earlier discharge.Similar pain control is possible for other ophthalmologic surgery.Because the oral medications used in this study were administered in capsules, the results may have been different if clinically available preparations had been tested.
VEGF-D Is the Strongest Angiogenic and Lymphangiogenic Effector Among VEGFs Delivered Into Skeletal Muscle via Adenoviruses
Authors: Tuomas T. Rissanen, Johanna E. Markkanen, Marcin Gruchala, Tommi Heikura, Antti Puranen, Mikko I. Kettunen, Ivana Kholová, Risto A. Kauppinen, Marc G. Achen, Steven A. Stacker, Kari Alitalo, Seppo Ylä-Herttuala
Journal: Circulation Research (2003)

Optimal angiogenic and lymphangiogenic gene therapy requires knowledge of the best growth factors for each purpose. We studied the therapeutic potential of human vascular endothelial growth factor (VEGF) family members VEGF-A, VEGF-B, VEGF-C, and VEGF-D as well as a VEGFR-3–specific mutant (VEGF-C 156S ) using adenoviral gene transfer in rabbit hindlimb skeletal muscle. The significance of proteolytic processing of VEGF-D was explored using adenoviruses encoding either full-length or mature (ΔNΔC) VEGF-D. Adenoviruses expressing potent VEGFR-2 ligands, VEGF-A and VEGF-D ΔNΔC , induced the strongest angiogenesis and vascular permeability effects as assessed by capillary vessel and perfusion measurements, modified Miles assay, and MRI. The most significant feature of angiogenesis induced by both VEGF-A and VEGF-D ΔNΔC was a remarkable enlargement of microvessels with efficient recruitment of pericytes suggesting formation of arterioles or venules. VEGF-A also moderately increased capillary density and created glomeruloid bodies, clusters of tortuous vessels, whereas VEGF-D ΔNΔC –induced angiogenesis was more diffuse. Vascular smooth muscle cell proliferation occurred in regions with increased plasma protein extravasation, indicating that arteriogenesis may be promoted by VEGF-A and VEGF-D ΔNΔC . Full-length VEGF-C and VEGF-D induced predominantly and the selective VEGFR-3 ligand VEGF-C 156S exclusively lymphangiogenesis. Unlike angiogenesis, lymphangiogenesis was not dependent on nitric oxide. The VEGFR-1 ligand VEGF-B did not promote either angiogenesis or lymphangiogenesis. Finally, we found a positive correlation between capillary size and vascular permeability. This study compares, for the first time, angiogenesis and lymphangiogenesis induced by gene transfer of different human VEGFs, and shows that VEGF-D is the most potent member when delivered via an adenoviral vector into skeletal muscle.
Type III collagen aminopropeptide and laminin PI levels in serum of patients with silicosis-associated and idiopathic systemic scleroderma
Authors: K. HERRMANN, E. SCHULZE, M. HECKMANN, I. SCHUBERT, M. MEURER, V. ZIEGLER, U.F. HAUSTEIN, J. MEHLHORN, TH. KRIEG
Journal: British Journal of Dermatology (1990)

A group of 191 patients with systemic scleroderma and 12 patients with silicosis-associated scleroderma were investigated for connective tissue turnover. The serum levels of type III collagen aminopropeptide (P-III-P), the laminin P1 (Lam P1) fragment and the acid lysosomal β-galactosidase (β-Gal) were determined by specific radioimmunoassays and spectrofluorometry, respectively. Increased levels of type III collagen aminopropeptide strongly correlated with enhanced activity of β-galactosidase. Both parameters correlated with the clinical course in idiopathic systemic scleroderma and in silicosis-associated scleroderma. Serum levels of Lam P1 were also found to be elevated in both groups, although there was no correlation with the severity of the disease. Autoantibodies directed against the DNA topoisomerase Scl-70 and against centromeric proteins were found in a similar range in patients with idiopathic systemic and silicosis-associated scleroderma. These results suggest that P-III-P, Lam P1 and β-Gal are useful serological markers of fibrotic activity and demonstrate similarities between idiopathic systemic scleroderma and scleroderma associated with silica-dust exposure.