tbuckley/cabot-search huggingface dataset:
Statistical tests for detecting gene conversion.
Authors: S Sawyer
Journal: Molecular Biology and Evolution (1989)

Statistical tests for detecting gene conversion are described for a sample of homologous DNA sequences. The tests are based on imbalances in the distribution of segments on which some pair of sequences agrees. The methods automatically control for variable mutation rates along the genome and do not depend on a priori choices of potentially monophyletic subsets of the sample. The tests show strong evidence for multiple intragenic conversion events at two loci in Escherichia coli. The gnd locus in E. coli shows a highly significant excess of maximal segments of length 70-200 bp, which suggests conversion events of that size. The data also indicate that the rate of these short conversion events might be of the order of neutral mutation rate. There is also evidence for correlated mutation in adjacent codon positions. The same tests applied to a locus in an RNA virus were negative.
Fate of the C3H Mammary Tumor Agent in Mice of Strains C57BL, I, and BALB/c
Authors: Howard B. Andervont
Journal: JNCI Journal of the National Cancer Institute (1964)

Mice of low-mammary-tumor inbred strains C57BL, I, and BALB/c obtained the mammary tumor agent by foster-nursing on high-mammary-tumor strain C3H. These were the only mice that ingested C3H milk. They and their descendants were bred brother × sister and observed for the occurrence of mammary tumors. The agent disappeared from, or became inactive in, strains C57BL and I within a few generations. This confirmed earlier findings with C57BL mice and established a line whose ancestors carried the agent. Thirty-five generations of this line included 300 breeding females; none developed a mammary tumor. A BALB/c female obtained the C3H agent in 1940. Her descendants for 59 generations have shown a high incidence of mammary tumors. The last 37 completed generations are recorded herein. According to the tumor incidence and the average age at which tumors appeared in successive generations, the C3H agent has not increased or decreased in activity during passage through 59 generations of BALB/c mice.
Increased nitric oxide—dependent vasorelaxation in aortic rings of cirrhotic rats with ascites
Authors: Joan Clària, Wladimiro Jiménez, Josefa Ros, Montserrat Rigol, Paolo Angeli, Vicente Arroyo, Francisca Rivera, Joan Rodés
Journal: Hepatology (1994)

To assess whether aortic vessels of rats with cirrhosis and ascites possess an enhanced vascular response to endothelium-derived, nitric oxide-dependent vasodilators, we performed relaxation studies in isolated aortic rings of 21 control rats and 24 rats with carbon tetrachloride-induced cirrhosis and ascites. We carried out studies after contracting the vessels with norepinephrine. We measured endothelium-dependent vasodilator response by administering increasing concentrations of acetylcholine (10(-6) to 10(-2) mol/L) and ADP (10(-7) to 10(-4) mol/L). We evaluated endothelium-independent response by giving increased concentration of sodium nitrite (10(-5) to 10(-2) mol/L). The maximal absolute tension developed in response to norepinephrine was significantly decreased in cirrhotic rings (816 +/- 72 mg, p < 0.025) compared with control (1,425 +/- 75 mg) rings. Dose-response curves for endothelium-dependent vasodilators were shifted to the left in aortic rings of cirrhotic rats, and EC50 for acetylcholine and ADP were significantly decreased in cirrhotic (0.8 +/- 0.15 mmol/L and 0.42 +/- 0.16 mumol/L, p < 0.025 and p < 0.01, respectively) than in control rings (1.91 +/- 0.33 mmol/L and 3.09 +/- 0.82 mumol/L). In both acetylcholine- and ADP-stimulated vessels, differences between cirrhotic and control rings disappeared after nitric oxide synthesis inhibition with N omega-nitro-L-arginine (10(-4) mol/L). No difference in the relaxing effect of sodium nitrite was observed between cirrhotic and control rings. These results therefore demonstrate for the first time enhanced in vitro vascular responsiveness to nitric oxide-dependent vasodilators in rats with cirrhosis and ascites, giving further support to the concept that nitric oxide activity is increased in cirrhosis.
Prevention of hepatitis C virus infection and spread in human liver chimeric mice by an anti‐CD81 monoclonal antibody
Authors: Changhua Ji, Yang Liu, Chandra Pamulapati, Sandhya Bohini, Georg Fertig, Michael Schraeml, Werner Rubas, Michael Brandt, Stefan Ries, Han Ma, Klaus Klumpp
Journal: Hepatology (2014)

CD81 is a required receptor for hepatitis C virus (HCV) infection of human hepatocytes in vitro . We generated several high‐affinity anti‐human CD81 monoclonal antibodies (mAbs) that demonstrated potent, specific, and cross‐genotype inhibition of HCV entry. One of these mAbs, K04, was administered to human liver chimeric mice before or after HCV infection to determine its ability to prevent HCV infection or spread of HCV infection, respectively. All vehicle control mice established HCV infection, reaching steady‐state levels of serum HCV RNA by day 21. Pretreatment of mice with K04 prevented HCV infection in all mice (n = 5). Treatment of mice with mAb K04 every 3 days for 21 days, starting at 6 hours postinfection, resulted in effective inhibition of virus spread. In 3 mice that were sacrificed on day 24, serum HCV levels remained detectable, below the limit of quantification (LOQ), indicating that infection was established, but virus spread was blocked, by the anti‐CD81 mAb. In 5 additional mice that were followed for a longer time, virus remained detectable, below LOQ, until days 24 and 30 in 4 of 5 mice. In the fifth mouse, viral load was quantifiable, but reduced to 64‐fold below the mean viral load in vehicle control at day 24. In addition, 2 of 5 mice cleared the infection by day 30 and 1 mouse had undetectable virus load from day 6 onward. Conclusion : These results demonstrate that CD81 is required for HCV infection and virus spread in vivo , and that anti‐CD81 antibodies such as K04 may have potential as broad‐spectrum antiviral agents for prevention and treatment of HCV infection. (H epatology 2015;61:1136–1144)
In vivo function of surfactants containing phosphatidylcholine analogs.
Authors: L Dizon-Co, M Ikegami, T Ueda, A H Jobe, W H Lin, J G Turcotte, R H Notter, E D Rider
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Increased phospholipase A2 activity demonstrated in some forms of lung injury may contribute to surfactant dysfunction. Phospholipase A2-resistant analogs of dipalmitoylphosphatidylcholine (DPPC) with surfactant properties might therefore be useful lipid components of treatment surfactants for certain lung injuries. The in vivo function of surfactants containing DPPC or the phospholipase-resistant analogs dihexadecylphosphatidylcholine (DEPC) or dihexadecylphosphonotidylcholine (DEPnC), with or without surfactant proteins B and C (SP-B+C), was thus evaluated in preterm rabbits (27 days' gestation). Rabbits randomly received one of seven surfactants (DPPC, DEPC, DEPnC, DPPC+SP-B+C, DEPC+SP-B+C, DEPnC+SP-B+C, or lipid extract surfactant [LES]) or 0.45% NaCl (control) and were ventilated for 30 min. Lipid-only surfactants decreased ventilatory pressures (peak inspiratory pressures minus positive end-expiratory pressure) relative to control (p < 0.05). Addition of SP-B+C further decreased ventilatory pressures to levels similar to LES (p < 0.01 versus control, lipid-only surfactants). Lung dynamic compliances and postventilation pressure-volume curves improved in the following order: LES, SP-B+C lipid surfactants > lipid-only surfactants > control (p < 0.05). All surfactant preparations decreased intravascular 125I-albumin recoveries in the lungs relative to control (p < 0.01 for all surfactants versus control). These results indicate that DEPC and DEPnC were as effective as DPPC as lipid components of synthetic surfactants. And like DPPC, the analogs interacted with isolated SP-B+C and improved in vivo function to levels comparable to LES.
Clinical and genetic characteristics of hereditary pancreatitis in Europe
Authors: Nathan Howes, Markus M. Lerch, William Greenhalf, Deborah D. Stocken, Ian Ellis, Peter Simon, Kaspar Truninger, Rudi Ammann, Giorgio Cavallini, Richard M. Charnley, Generoso Uomo, Miriam Delhaye, Julius Spicak, Brendan Drumm, Jan Jansen, Roger Mountford, David C. Whitcomb, John P. Neoptolemos
Journal: Clinical Gastroenterology and Hepatology (2004)
Response to Letters Regarding Article, “Unexpected Effect of Proton Pump Inhibitors: Elevation of the Cardiovascular Risk Factor Asymmetric Dimethylarginine”
Authors: Yohannes T. Ghebremariam, Paea LePendu, Jerry C. Lee, Daniel A. Erlanson, Anna Slaviero, Nigam H. Shah, James M. Leiper, John P. Cooke
Journal: Circulation (2014)

We agree with the authors that the proton pump inhibitors (PPIs) may adversely influence cardiovascular physiology in multiple ways.We found that PPIs reduce the enzymatic activity of dimethylarginine dimethylaminohydrolase.In this way, PPIs increase plasma levels of asymmetrical dimethylarginine (ADMA). 1 Because it inhibits the generation of vascular nitric oxide (NO), ADMA would be expected to increase platelet interaction with the vessel wall.Chyrchel and colleagues correctly point out that our findings may explain why PPIs attenuate the benefit of clopidogrel, as well as other P2Y 12 antiplatelet agents not dependent on CYP2C19 for their activity.We thank Montenegro and Lundberg for pointing out that NO may be generated in the stomach by the reduction of ingested nitrite, an effect that depends on low gastric pH.Dietary nitrate and nitrite are absorbed in the gastrointestinal tract, concentrated in the saliva as nitrite by the action of oral bacteria, and then converted to nitrous acid in the stomach.The spontaneous decomposition of nitrous acid generates NO.Gastric NO is known to increase blood flow, protect the gastric mucosa, and provide defense against pathogenic microorganisms.Accordingly, Montenegro and Lundberg raise the concern that PPIs could impair this exogenous nitrate/nitrite/NO cycle.Pinheiro and coworkers echo this concern and point out that the PPI esomeprazole has been observed to reduce the antihypertensive benefit of oral nitrates.The adverse effect of PPIs on this pathway may be of equal or greater importance to what we described.The ingestion of nitrate and nitrite may be critical to the cardiovascular benefits of diets rich in leafy greens and root vegetables as in the Dietary Approaches to Stop Hypertension study. 2 In addition, PPIs could influence circulating ADMA through their interference with the absorption of vitamin B 12 . 3This vitamin is required for the conversion of homocysteine to cysteine.Elevated plasma homocysteine levels increase plasma levels of ADMA and may increase the susceptibility to coronary artery disease. 4We have observed previously that an acute increase in homocysteine level acutely increases plasma ADMA and impairs endothelium-dependent vasodilation. 4o conclude, we and the other respondents agree that the PPIs may dysregulate interdependent pathways that regulate vascular NO generation.As a result, chronic exposure to PPIs might be expected to impair vascular homeostasis and potentially expose consumers to an increased risk of major adverse cardiovascular events.We plan to publish pharmacovigilance data regarding this question.The accumulating data raise a concern for the medical community and regulatory bodies regarding the cardiovascular safety of these agents.
Scavenger Receptor B1 is a Potential Biomarker of Human Nasopharyngeal Carcinoma and Its Growth is Inhibited by HDL-mimetic Nanoparticles
Authors: Ying Zheng, Yanyan Liu, Honglin Jin, Shaotao Pan, Yuan Qian, Chuan Huang, Yixin Zeng, Qingming Luo, Musheng Zeng, Zhihong Zhang
Journal: Theranostics (2013)

Nasopharyngeal carcinoma (NPC) is a very regional malignant head and neck cancer that has attracted widespread attention for its unique etiology, epidemiology and therapeutic options.To achieve high cure rates in NPC patients, theranostic approaches are actively being pursued and improved efforts remain desirable in identifying novel biomarkers and establishing effective therapeutic approaches with low long-term toxicities.Here, we discovered that the scavenger receptor class B type I (SR-B1) was overexpressed in all investigated NPC cell lines and 75% of NPC biopsies, demonstrating that SR-B1 is a potential biomarker of NPC.Additional functional analysis showed that SR-B1 has great effect on cell motility while showing no significant impact on cell proliferation.As high-density lipoproteins (HDL) exhibit strong binding affinities to SR-B1 and HDL mimetic peptides are reportedly capable of inhibiting tumor growth, we further examined the SR-B1 targeting ability of a highly biocompatible HDL-mimicking peptide-phospholipid scaffold (HPPS) nanocarrier and investigated its therapeutic effect on NPC.Results show that NPC cells with higher SR-B1 expression have superior ability in taking up the core constituents of HPPS.Moreover, HPPS inhibited the motility and colony formation of 5-8F cells, and significantly suppressed the NPC cell growth in nude mice without inducing tumor cell necrosis or apoptosis.These results indicate that HPPS is not only a NPC-targeting nanocarrier but also an effective anti-NPC drug.Together, the identification of SR-B1 as a potential biomarker and the use of HPPS as an effective anti-NPC agent may shed new light on the diagnosis and therapeutics of NPC.
IgE-binding epitopes of enolases, a class of highly conserved fungal allergens
Authors: Birgit Simon-Nobbe, Gerald Probst, Andrey V. Kajava, Hannes Oberkofler, Markus Susani, Reto Crameri, Fátima Ferreira, Christof Ebner, Michael Breitenbach
Journal: Journal of Allergy and Clinical Immunology (2000)
Densitometric diagnosis of osteoporosis in patients with chronic obstructive pulmonary disease
Authors: Ekaterina Kochetova
Journal: European Respiratory Journal (2012)

The aim of the Study : to study the state of bone mineral density (BMD) in patients with chronic obstructive pulmonary disease (COPD).  Materials and methods:  studied 104 patients with COPD. The study group comprised men with long smoking history. Mean age 61,2 ± 5,7 years. The study of respiratory function was performed on a multi-type installation «Master-Lab/Jaeger». The study of bone mineral density (BMD) of lumbar spine and proximal femur was performed by X-ray absorptiometry at the densitometer «Lunar DPX-NT». The frequency of osteoporosis was assessed in the whole group and separately for each stage of COPD.  Results:  In the whole group was most impressed by osteoporosis, lumbar spine - in 37,2% of cases, osteoporosis of the femoral neck - in 19,77% of cases. The lowest BMD were observed in patients with stage 4 COPD (p  Conclusion:  densitometry is an important method of diagnostics of osteoporosis and should be applied in full in COPD patients.
Airspace size in lungs of lifelong non-smokers: effect of age and sex.
Authors: M Gillooly, D Lamb
Journal: Thorax (1993)

BACKGROUND: Emphysema is defined as the abnormal enlargement of airspaces distal to the terminal bronchiole, but the limits of normality of airspace size have never been defined. The aims of the study were to examine the effects of age and sex on airspace size in non-smokers and to define the limits of normal airspace size. METHODS: Airspace size was measured in terms of airspace wall surface area per unit volume of lung tissue (AWUV). AWUV was measured on histological sections of lung tissue with an automated scanning system, the fast interval processor. Thirty eight lifelong non-smokers were studied, 15 male and 23 female, with an age range of 21-93 years. Macroscopic emphysema was assessed semi-quantitatively on the midsagittal slice of each lung specimen. RESULTS: The relation between mean AWUV and age was negative (r = -0.78). This relation was linear, and the 95% prediction limits of its regression line were used as the limits of normality of AWUV in this sample. The AWUV-age relationship was similar in the men and women studied. Localised areas of macroscopic emphysema were found in three specimens whose mean AWUV measurements were within the normal range. CONCLUSIONS: There is a normal increase in airspace size associated with advancing age in adult lungs. The limits of normal AWUV between ages 21 and 93 years have been defined, and it is proposed that lungs with a mean AWUV below the 95% prediction limit should be considered as having emphysema.
Impact of Diabetes and Hepatitis after Kidney Transplantation on Patients Who Are Affected by Hepatitis C Virus
Authors: Kevin C. Abbott, Krista L. Lentine, Jay R. Bucci, Lawrence Y. Agodoa, Jonathan M. Koff, Kent C. Holtzmuller, Mark A. Schnitzler
Journal: Journal of the American Society of Nephrology (2004)

Complications associated with use of donor hepatitis C–positive kidneys (DHCV+) have been attributed primarily to posttransplantation liver disease (as a result of hepatitis C disease). The role of posttransplantation diabetes has not been explored in this setting. With the use of the United States Renal Data System database, 28,942 Medicare KT recipients were studied from January 1, 1996, through July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHR) for the association of sero-pairs for HCV (D+/R−, D+/R+, D−/R+ and D−/R−) with Medicare claims for de novo posttransplantation HCV and posttransplantation diabetes. The peak risk for posttransplantation HCV was in the first 6 mo after transplantation. The incidence of posttransplantation HCV after transplantation was 9.1% in D+/R−, 6.3% in D+/R+, 2.4% in D−/R+, and 0.2% in D−/R−. The incidence of posttransplantation diabetes after transplantation also peaked early and was 43.8% in D+/R−, 46.6% in D+/R+, 32.3% in D−/R+, and 25.4% in D−/R−. Associations for both complications were significant in adjusted analysis (Cox regression). Both posttransplantation HCV (AHR, 3.36; 95% confidence interval, 2.44 to 4.61) and posttransplantation diabetes (AHR, 1.81; 95% confidence interval, 1.54 to 2.11) were independently associated with an increased risk of death, but posttransplantation diabetes accounted for more years of life lost, particularly among recipients of DHCV+ kidneys. Posttransplantation diabetes may contribute substantially to the increased risk of death associated with use of DHCV+ kidneys and accounts for more years of life lost than posttransplantation HCV. Because HCV infection acquired after transplantation is so difficult to treat, methods that have been shown to reduce viral transmission warrant renewed attention.
Secondary prevention in coronary heart disease
Authors: J. Morrell, R E Ferner
Journal: BMJ (1999)

Proportions of cases (babies with neonatal encephalopathy) and controls having complicated* and uncomplicated † deliveries in Badawi et al's study No (%) of cases (n=164) No (%) of controls (n=400) Unadjusted odds ratio (95% CI) Complicated delivery 79 (48) 101 (25) 2.75 (1.88 to 4.02) Uncomplicated delivery 85 (52) 299 (75) 0.36 (0.25 to 0.53) *Complicated deliveries: instrumental deliveries
Prognostic factors in patients with endocrine tumours of the duodenopancreatic area
Authors: I Madeira, B Terris, M Voss, A Denys, A Sauvanet, J-F Flejou, V Vilgrain, J Belghiti, P Bernades, P Ruszniewski
Journal: Gut (1998)

Background —The development of endocrine tumours of the duodenopancreatic area (ETDP) is thought to be slow, but their natural history is not well known. The aim of this study was to determine the factors that influence survival of patients with ETDP. Patients/Methods —Eighty two patients with ETDP (44 non-functioning tumours, 23 gastrinomas, seven calcitonin-secreting tumours, four glucagonomas, three insulinomas, one somatostatinoma) followed from October 1991 to June 1997 were included in the study. The following factors were investigated: primary tumour size, hormonal clinical syndrome, liver metastases, lymph node metastases, extranodular/extrahepatic metastases, progression of liver metastases, local invasion, complete resection of the primary tumour, and degree of tumoral differentiation. The prognostic significance of these factors was investigated by uni- and multi-variate analysis. Results —Twenty eight patients (34%) died within a median of 17 months (range 1–110) from diagnosis. Liver metastases (p = 0.001), lymph node metastases (p = 0.001), progression of liver metastases (p&lt;0.00001), lack of complete resection of the primary tumour (p = 0.001), extranodular/extrahepatic metastases (p = 0.001), local invasion (p = 0.001), primary tumour size ⩾3 cm (p = 0.001), non-functioning tumours (p = 0.02), and poor tumoral differentiation (p = 0.006) were associated with an unfavourable outcome by univariate analysis. Multivariate analysis identified only liver metastases (risk ratio (RR) = 8.3; p&lt;0.0001), poor tumoral cell differentiation (RR = 8.1; p = 0.0001), and lack of complete resection of the primary tumour (RR = 4.8; p = 0.0007) as independent risk factors. Five year survival rates were 40 and 100% in patients with and without liver metastases, 85 and 42% in patients with and without complete resection of primary tumour, and 17 and 71% in patients with poor and good tumour cell differentiation respectively. Conclusion —Liver metastases are a major prognostic factor in patients with ETDP. Progression of liver metastases is also an important factor which must be taken into account when deciding on the therapeutic approach. The only other independent prognostic factors are tumoral cell differentiation and complete resection of the primary tumour.
Melanocytic naevi with globular and reticular dermoscopic patterns display distinct<scp>BRAF</scp>V600E expression profiles and histopathological patterns
Authors: M.A. Marchetti, M.H. Kiuru, K.J. Busam, A.A. Marghoob, A. Scope, S.W. Dusza, M.A. Cordova, M. Fonseca, X. Wu, A.C. Halpern
Journal: British Journal of Dermatology (2014)

BRAF (v-raf murine sarcoma viral oncogene homologue B) V600E mutations have been detected with high frequency in melanocytic naevi. Few studies have stratified analyses by naevus dermoscopic pattern.To determine the frequency of BRAF V600E expression and histopathological pattern in acquired melanocytic naevi distinguished by a globular vs. reticular dermoscopic pattern.We retrospectively identified histologically proven melanocytic naevi with banal reticular or globular dermoscopic patterns and evaluated BRAF V600E expression using immunohistochemistry.BRAF V600E expression was detected in 11 of 12 globular naevi vs. four of 13 reticular naevi (91·7% vs. 30·1%, P = 0·004). A predominantly dermal growth pattern (P < 0·001) and the presence of large junctional nests (P = 0·017) were each associated with a globular dermoscopic pattern. The presence of either a predominantly dermal growth pattern or large junctional nests was found in 13 of 15 naevi positive for BRAF V600E and in two of 10 naevi negative for BRAF V600E (86·7% vs. 20%, P = 0·002).The frequency of BRAF V600E mutations differs in naevi distinguished by unique dermoscopic structures and microanatomical growth patterns. Globular naevi, which most often histologically correspond to a predominantly dermal growth pattern and/or the presence of large junctional nests, are significantly more likely to express BRAF V600E than reticular naevi. These preliminary results require validation, but may directly inform future studies of naevogenesis and melanoma genesis.