tbuckley/cabot-search huggingface dataset:
Inhibition of hepatitis C virus infection by anti‐claudin‐1 antibodies is mediated by neutralization of E2–CD81–Claudin‐1 associations†
Authors: Sophie E. Krieger, Mirjam B. Zeisel, Christopher Davis, Christine Thumann, Helen J. Harris, Eva K. Schnober, Christopher Mee, Eric Soulier, Cathy Royer, Mélanie Lambotin, Fritz Grunert, Viet Loan Dao Thi, Marlène Dreux, François‐Loïc Cosset, Jane A. McKeating, Catherine Schuster, Thomas F. Baumert
Journal: Hepatology (2009)

The tight junction protein claudin-1 (CLDN1) has been shown to be essential for hepatitis C virus (HCV) entry—the first step of viral infection. Due to the lack of neutralizing anti-CLDN1 antibodies, the role of CLDN1 in the viral entry process is poorly understood. In this study, we produced antibodies directed against the human CLDN1 extracellular loops by genetic immunization and used these antibodies to investigate the mechanistic role of CLDN1 for HCV entry in an infectious HCV cell culture system and human hepatocytes. Antibodies specific for cell surface–expressed CLDN1 specifically inhibit HCV infection in a dose-dependent manner. Antibodies specific for CLDN1, scavenger receptor B1, and CD81 show an additive neutralizing capacity compared with either agent used alone. Kinetic studies with anti-CLDN1 and anti-CD81 antibodies demonstrate that HCV interactions with both entry factors occur at a similar time in the internalization process. Anti-CLDN1 antibodies inhibit the binding of envelope glycoprotein E2 to HCV permissive cell lines in the absence of detectable CLDN1-E2 interaction. Using fluorescent-labeled entry factors and fluorescence resonance energy transfer methodology, we demonstrate that anti-CLDN1 antibodies inhibit CD81-CLDN1 association. In contrast, CLDN1-CLDN1 and CD81-CD81 associations were not modulated. Taken together, our results demonstrate that antibodies targeting CLDN1 neutralize HCV infectivity by reducing E2 association with the cell surface and disrupting CD81-CLDN1 interactions. Conclusion: These results further define the function of CLDN1 in the HCV entry process and highlight new antiviral strategies targeting E2-CD81-CLDN1 interactions. (HEPATOLOGY 2010.)
Changes in incidence, survival and mortality of prostate cancer in Europe and the United States in the PSA era: additional diagnoses and avoided deaths
Authors: C. Neppl-Huber, M. Zappa, J.W. Coebergh, E. Rapiti, J. Rachtan, B. Holleczek, S. Rosso, T. Aareleid, H. Brenner, A. Gondos
Journal: Annals of Oncology (2011)
Defining the Relationship Between Plasma Glucose and HbA1c
Authors: Curt L. Rohlfing, Hsiao-Mei Wiedmeyer, Randie R. Little, Jack D. England, Alethea Tennill, David E. Goldstein
Journal: Diabetes Care (2002)

OBJECTIVE— To define the relationship between HbA1c and plasma glucose (PG) levels in patients with type 1 diabetes using data from the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS— The DCCT was a multicenter, randomized clinical trial designed to compare intensive and conventional therapies and their relative effects on the development and progression of diabetic complications in patients with type 1 diabetes. Quarterly HbA1c and corresponding seven-point capillary blood glucose profiles (premeal, postmeal, and bedtime) obtained in the DCCT were analyzed to define the relationship between HbA1c and PG. Only data from complete profiles with corresponding HbA1c were used (n = 26,056). Of the 1,441 subjects who participated in the study, 2 were excluded due to missing data. Mean plasma glucose (MPG) was estimated by multiplying capillary blood glucose by 1.11. Linear regression analysis weighted by the number of observations per subject was used to correlate MPG and HbA1c. RESULTS— Linear regression analysis, using MPG and HbA1c summarized by patient (n = 1,439), produced a relationship of MPG (mmol/l) = (1.98 ○1 HbA1c) - 4.29 or MPG (mg/dl) = (35.6 ○1 HbA1c) - 77.3, r = 0.82). Among individual time points, afternoon and evening PG (postlunch, predinner, postdinner, and bedtime) showed higher correlations with HbA1c than the morning time points (prebreakfast, postbreakfast, and prelunch). CONCLUSIONS— We have defined the relationship between HbA1c and PG as assessed in the DCCT. Knowing this relationship can help patients with diabetes and their healthcare providers set day-to-day targets for PG to achieve specific HbA1c goals.
Visceral Adipose Tissue Cutoffs Associated With Metabolic Risk Factors for Coronary Heart Disease in Women
Authors: Barbara J. Nicklas, Brenda W.J.H. Penninx, Alice S. Ryan, Dora M. Berman, Nicole A. Lynch, Karen E. Dennis
Journal: Diabetes Care (2003)

OBJECTIVE—This study determined whether there is a critical level of visceral adipose tissue (VAT) associated with elevated coronary heart disease (CHD) risk factors in a cohort of women &amp;gt;45 years of age. RESEARCH DESIGN AND METHODS—Measurements of body composition (dual-energy X-ray absorptiometry), body fat distribution (computed tomography), fasting and 2-h postprandial (75-g) glucose concentrations, and fasting lipoprotein lipid and insulin concentrations were performed in 233 perimenopausal (9%) and postmenopausal women (age 59 ± 6 years, 79% Caucasian, 16% on hormone replacement therapy). RESULTS—Women in the lowest VAT quintile (≤105 cm2) had higher concentrations of HDL and HDL2 cholesterol, lower LDL/HDL cholesterol ratios and triglyceride concentrations, and lower fasting glucose and insulin concentrations than women in the remaining four quintiles (P values &amp;lt;0.05–0.001). Women in the second lowest VAT quintile (106–139 cm2) had higher HDL and HDL2 cholesterol and lower LDL/HDL ratios than women with a VAT ≥163 cm2 (P &amp;lt; 0.05). Logistic regression analyses showed that women with a VAT of 106–162 cm2 are 2.5 times more likely to have a low HDL cholesterol (P &amp;lt; 0.05), while women with a VAT ≥163 cm2 are 5.5 times more likely to have a low HDL cholesterol (P &amp;lt; 0.01) and ∼4.0 times more likely to have a high LDL/HDL ratio (P &amp;lt; 0.05) compared with women with a VAT ≤105 cm2. Women with a VAT ≥163 cm2 are at a higher risk of having impaired glucose tolerance (P &amp;lt; 0.01). CONCLUSIONS—A VAT ≥106 cm2 is associated with an elevated risk, and a VAT ≥163 cm2 with an even greater risk, for these metabolic CHD risk factors compared with women with a VAT ≤105 cm2. These values may prove useful for defining “visceral obesity” and for identifying women most likely to benefit from preventative interventions.
The Complete Mitochondrial DNA Sequence of the Horseshoe Crab Limulus polyphemus
Authors: Dennis V. Lavrov, Jeffrey L. Boore, Wesley M. Brown
Journal: Molecular Biology and Evolution (2000)

We determined the complete 14,985-nt sequence of the mitochondrial DNA of the horseshoe crab Limulus polyphemus (Arthropoda: Xiphosura). This mtDNA encodes the 13 protein, 2 rRNA, and 22 tRNA genes typical for metazoans. The arrangement of these genes and about half of the sequence was reported previously; however, the sequence contained a large number of errors, which are corrected here. The two strands of Limulus mtDNA have significantly different nucleotide compositions. The strand encoding most mitochondrial proteins has 1.25 times as many A's as T's and 2.33 times as many C's as G's. This nucleotide bias correlates with the biases in amino acid content and synonymous codon usage in proteins encoded by different strands and with the number of non–Watson-Crick base pairs in the stem regions of encoded tRNAs. The sizes of most mitochondrial protein genes in Limulus are either identical to or slightly smaller than those of their Drosophila counterparts. The usage of the initiation and termination codons in these genes seems to follow patterns that are conserved among most arthropod and some other metazoan mitochondrial genomes. The noncoding region of Limulus mtDNA contains a potential stem-loop structure, and we found a similar structure in the noncoding region of the published mtDNA of the prostriate tick Ixodes hexagonus. A simulation study was designed to evaluate the significance of these secondary structures; it revealed that they are statistically significant. No significant, comparable structure can be identified for the metastriate ticks Rhipicephalus sanguineus and Boophilus microplus. The latter two animals also share a mitochondrial gene rearrangement and an unusual structure of mt-tRNA(C) that is exactly the same association of changes as previously reported for a group of lizards. This suggests that the changes observed are not independent and that the stem-loop structure found in the noncoding regions of Limulus and Ixodes mtDNA may play the same role as that between trnN and trnC in vertebrates, i.e., the role of lagging strand origin of replication.
AN OPERATION FOR INGUINAL HERNIA
Authors: G. L. Cheatle
Journal: BMJ (1921)

I025'o:~~~~~~~~~~~~~~~~~~~~' P0114tf O-' 54.1 (Case i), and in a third of 24 (Case IIi) failed to destroy the bacillus..2.The gastric secretion may possibly have destroyed the tubercle bacilli in a very weak emulsion to which it was exposed under similar conditions, but the number of bacilli used (100) was so small that it cannot be considered a fair test, and even tlle control test with this weak emulsion proved negative in a guinea-pig.3. Thle protectioni against the tubercle bacillus afforded by the gastric secretion is apparently by no means perfect.But it muust be remembered tllat tlle dilution of contents and the motor activity of the stomach probably play a large part in this mechanism of protection, and these latter factors cannot be satisfactorily experimented upon in vitro.Thiese results are in general agreement witlh tlle con- clusions arrived at by Allan Maefadyen 6 under different conditions and with bacteria other than B. tuberculosi8 as long ago as 1887.4. In the four cases examilned the untreated gastric juice contained no tuberele bacilli as judged by the inoculation test.We linow of no records which slhow wlhetlher or no tubercle bacilli have been found in gastric juice in persons not suffering from clinical tuberculosis.Tllis point mnay have important bearing on the portals of entry of the bacillus.
Acute lymphoblastic leukemia in idiopathic refractory sideroblastic anemia: Evidence for a common lymphoid and myeloid progenitor cell
Authors: James C. Barton, Marcel E. Conrad, Richard T. Parmley
Journal: American Journal of Hematology (1980)

Abstract Acute leukemia of myeloblastic or erythroblastic morphology occasionally occurs as a complication of idiopathic refractory sideroblastic anemia, but the development of acute lymphoblastic leukemia has not been previously reported in these cases. A patient with idiopathic refractory sideroblastic anemia is described in whom acute lymphoblastic leukemia occurred. The leukemic cells were characterized by typical lymphoblastic morphology on Wright's stain, periodic acid‐Schiff‐positive cytoplasmic clumps, elevated levels of deoxynucleotidyl transferase (143 units/10 8 cells), high numbers of specific glucocorticoid binding sites (16,845 sites/cell, Kd = 5.40 × 10 −9 M), non‐B, non‐T cell immunologic characteristics and clinical responsiveness to therapy with vincristine, prednisone, and methotrexate. Ultrastructural studies of the lymphoblasts identified ferruginous material in lysosomes and occasional mitochondria similar to but less abundant than that seen in abnormal sideroblasts. The concurrence of these two disorders supports the theory that in humans both lymphoid and myeloid cell lines arise from a common pluripotent stem cell.
The accuracy of guestimates
Authors: I. McLean, C M. Anderson, C. White
Journal: Journal of the Royal Society of Medicine (2003)

At times a clinician must describe the size of a lesion when measurement presents difficulties. A ‘guestimate’ may then be recorded. We tested the accuracy of forensic clinicians (10 physicians and 1 nurse) in guestimating the sizes of ten test objects, comparing their performance with 13 individuals from other professions. The participants were permitted to handle the objects but not to use a measuring device. For three of the objects (a balloon, a scratch and a coin) the entire sample of participants significantly overestimated size, by 13-22%. Both participant groups overestimated the size of a scratch, the clinicians being more accurate but not significantly so. Guestimates should be avoided unless the use of a ruler or tape measure will be against the interests of the client.
PWE-035 Centralisation of upper GI cancer services—is the hub really better than the spoke?
Authors: S Monkhouse, J Torres-Grau, D Bawden, C Ross, R Krysztopik
Journal: Gut (2012)

<h3>Introduction</h3> The aim of this study was to assess whether patients diagnosed with oesophageal or gastric cancer at a local district general hospital (the “spoke”) have a similar temporal pathway through the decision making and treatment process compared to those patients presenting at the centralised, tertiary hospital (the “hub”). <h3>Methods</h3> Between April 2010 and April 2011, patients with a new diagnosis of oesophago-gastric cancer from both the hub and spoke hospitals were analysed. Data regarding diagnosis, time from diagnosis to multidisciplinary meeting (MDM) discussion and time from MDM decision to first treatment were all recorded. Statistical analysis was performed using parametric two-tailed t-test to assess significance. <h3>Results</h3> There was a statistically significant increase in the time from diagnosis to MDM discussion at the spoke hospital compared to the hub (13.3 days vs +25.67 days; p=0.001). However, time to first treatment (surgery, palliative therapy, neo-adjuvant therapy or best supportive care) was significantly increased in the hub hospital compared to the spoke (43.4 days vs 25.5 days; p=0.023). <h3>Conclusion</h3> This study is the first of its kind to show that there is a disparity in the management pathways of patients who first present to a regional hospital rather than the tertiary centre. Patients at the spoke hospital have a longer lead time into the MDM but non-operative treatment appears to be delivered more quickly locally. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Polednak AP</b>. “Trends in survival for both histologic types of esophageal cancer in US surveillance, epidemiology and end results areas”. <i>Int J Cancer</i> 2003;<b>105</b>:98–100. 2. <b>Birkmeyer JD</b>, Stukel TA, Siewers AE, <i>et al.</i> Surgeon volume and operative mortality in the United States. <i>N Engl J Med</i> 2003;<b>349</b>:2117–27. 3. <b>Gill AJ</b>, Martin IG. Survival from upper gastrointestinal cancer in New Zealand: the effect of distance from a major hospital, socio-economic status, ethnicity, age and gender. <i>ANZ J Surg</i> 2002;<b>72</b>:643–6. 4. <b>Department of Health</b>. <i>Improving Outcomes in Upper Gastrointestinal Cancers</i>. London: Department of Health, 2001. 5. <b>Siriwardena AK</b>. Centralisation of upper gastrointestinal cancer surgery. <i>Ann R Coll Surg Engl</i> 2007;<b>89</b>:335–6. 6. <b>Siewert JR</b>, Stein HJ. Carcinoma of the gastroesophageal junction: classification, pathology and extent of resection. <i>Dis Esophagus</i> 1986;<b>9</b>:173–82. 7. <b>Mcleod U</b>, Mitchell ED, Burgess C, <i>et al.</i> Risk factors for delayed presentation and referral of symptomatic cancer: evidence for common cancers. <i>Br J Cancer</i> 2009;<b>101</b>(Suppl 2):S92–101. 8. <b>Forshaw MJ</b>, Gossage JA, Stephens J, <i>et al.</i> Centralisation of oesophagogastric cancer services—can specialist units deliver? <i>Ann R Coll Surg Engl</i> 2006;<b>88</b>:566–70.
Fibrinogen chapel hill: Hypodysfibrinogenemia with a tertiary polymerization defect
Authors: R. P. McDonagh, N. A. Carrell, H. R. Roberts, P. M. Blatt, Jan McDonagh
Journal: American Journal of Hematology (1980)

Abstract A patient with a functionally defective fibrinogen (fibrinogen Chapel Hill) has been investigated. Fibrinogen Chapel Hill is characterized by hypofibrinogenemia, with a plasma concentration about one third of normal, as measured both functionally and immunochemically. Fibronogen survival is normal; so also is fibrinopeptide release. A polymerization defect in this fibrinogen results in the delay of fibrin fibrils in solution to form a normal three‐dimensional gel. This defect is not associated with end‐to‐end aggregation or with lateral associations in solution. Delayed gelation results from an abnormality in a tertiary contact site involved in network branching, which is associated with the hydrophilic, carboxy‐terminal segment of the α chain. Fibrinogen Chapel Hill exhibits two additional abnormal responses, which are also associated with the same region. The early plasmin cleavages of fibrinogen and fragment X are delayed, and there is a concomitant delay in the appearance of fragments Y, D, and E. This fibrinogen also has an unusual sensitivity to Ancrod proteolysis, whereby Ancrod cleaves a large carboxy‐terminal segment of the α chain more rapidly than in normal fibrinogen. The abnormalities in fibrinogen Chapel Hill can be explained by a structural abnormality which is functionally related to an α chain associated polymerization domain.
Multislice CT scans and D-dimer assays may be the most practical strategy for diagnosing PE
Authors: Z Ahmed
Journal: Thorax (2005)

▴ Perrier A, Roy P-M, Sanchez O, et al . Multidector-row computed tomography in suspected pulmonary embolism. N Engl J Med2005;352:1760–8

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



This prospective management trial with a 3 month follow up examined whether the use of multidetector row computed tomographic (CT) scanning combined with d-dimer ruled out pulmonary embolism (PE) safely without the use of lower limb ultrasonography, which has previously been shown to be needed along with single detector row CT scanning.

756 patients (of the 1014 screened: exclusion criteria included contraindications to contrast CT and other reasons for not participating in the study) …

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Recurrence of Diffuse Panbronchiolitis after Lung Transplantation
Authors: M. A. Baz, P. S. Kussin, P. van Trigt, R. D. Davis, V. L. Roggli, V. F. Tapson
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Diffuse panbronchiolitis (DBP) is characterized by chronic inflammation of the upper and lower respiratory tract. DPB has been found almost exclusively in oriental populations. We describe the occurrence of a case of DPB in an African American patient who underwent bilateral sequential lung transplantation. Ten weeks after transplantation, DPB recurred in the lung allograft, with rapid and significant deterioration in graft function. Allograft function improved within a few weeks after beginning treatment with erythromycin. This early recurrence is suggestive of a systemic etiology of DPB. Although recurrence of other systemic diseases has been reported after lung transplantation, no previous patients have been reported with early functional deterioration based solely on disease recurrence.
Altered cAMP-mediated signalling and its role in the pathogenesis of dilated cardiomyopathy
Authors: M MOVSESIAN
Journal: Cardiovascular Research (2004)

Alterations in the level and function of proteins involved in cAMP-mediated signalling are important in the pathophysiology and treatment of dilated cardiomyopathy. What is unclear is the extent to which these alterations, which attenuate receptor-stimulated cAMP generation, contribute to the pathogenesis of dilated cardiomyopathy and the extent to which they constitute a beneficial compensatory response. Studies in animals involving overexpression and ablation of proteins or peptides involved in cAMP-mediated signalling have yielded disparate results that are difficult to reconcile with a simple hypothesis. Our ability to understand these differences is limited by the lack of information on how these different genetic manipulations affect the phosphorylation of individual substrates of protein kinase A (PK-A) through which cAMP signals are transduced. This is important in view of evidence that the phosphorylation of individual PK-A substrates can be regulated selectively in different intracellular compartments, and that the phosphorylation of some PK-A substrates is increased in dilated cardiomyopathy while the phosphorylation of others is reduced. Approaches that quantify changes in the phosphorylation of individual PK-A substrates in models of dilated cardiomyopathy will provide information that may allow a better understanding of the pathogenesis of the syndrome and a more rational approach to its treatment.
Role of endothelial-leukocyte adhesion molecule 1 (ELAM-1) in neutrophil-mediated lung injury in rats.
Authors: M S Mulligan, J Varani, M K Dame, C L Lane, C W Smith, D C Anderson, P A Ward
Journal: Journal of Clinical Investigation (1991)

Two murine monoclonal antibodies (CL-3 and CL-37, both F(ab')2) to human endothelial-leukocyte adhesion molecule-1 (ELAM-1) were found to react immunohistochemically with rat pulmonary artery endothelial cells that had been pretreated with tumor necrosis factor (TNF alpha). CL-3, but not CL-37, blocked in vitro adherence of neutrophils to TNF alpha-treated endothelial cells and the killing of TNF alpha-treated rat endothelial cells by phorbol ester activated neutrophils. In rats treated systemically with CL-3, there was a 70% reduction in accumulation of neutrophils in glycogen-induced peritoneal exudates. Treatment of animals with CL-37 anti-ELAM-1 did not reduce neutrophil accumulation under the same conditions. When IgG immune complex deposition was induced in dermis and in lungs of rats, treatment with CL-3 anti-ELAM-1 markedly reduced vascular injury as measured by changes in vascular permeability (leakage of 125I-albumin) and hemorrhage (extravasation of 51Cr-red blood cells). The protective effects of CL-3 anti-ELAM-1 were related to greatly diminished recruitment of neutrophils (as assessed morphologically, by tissue extraction of myeloperoxidase, and by retrieval, via bronchoalveolar lavage, of neutrophils from lung). CL-37 had no protective effects in vivo after deposition of immune complexes in lung. Using either CL-3 or CL-37 anti-ELAM-1, immunohistochemical analysis of lungs undergoing IgG immune complex-induced injury revealed a striking upregulation of ELAM-1 in the lung vasculature (venules and interstitial capillaries), with a peak intensity developing between 3 and 4 h after deposition of immune complexes in lung. Vascular beds of spleen, liver, and kidney failed to show upregulation of ELAM-1 under these same conditions. The immunohistochemical reactivity of rat lung was abolished if the anti-ELAM-1 preparation was first absorbed with monolayers of human umbilical vein endothelial cells that had been pretreated with TNF alpha. Untreated human endothelial cells failed to cause loss of lung reactivity of the anti-ELAM-1 preparation. These data indicate that ELAM-1 is upregulated in the pulmonary vasculature of rats during deposition of immune complexes and that ELAM-1 appears to play an obligate role in the recruitment of neutrophils.