tbuckley/cabot-search huggingface dataset:
Reversible Cysteine-Targeted Oxidation of Proteins during Renal Oxidative Stress
Authors: Philip Eaton, Miriam E. Jones, Emma McGregor, Michael J. Dunn, Nicola Leeds, Helen L. Byers, Kit-Yi Leung, Malcolm A. Ward, Julian R. Pratt, Michael J. Shattock
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Biotin-cysteine was used to study protein S-thiolation in isolated rat kidneys subjected to ischemia and reperfusion. After 40 min of ischemia, total protein S-thiolation increased significantly (P < 0.05), by 311%, and remained significantly elevated (P < 0.05), 221% above control, after 5 min of postischemic reperfusion. Treatment of protein samples with 2-mercaptoethanol abolished the S-thiolation signals detected, consistent with the dependence of the signal on the presence of a disulfide bond. With the use of gel filtration chromatography followed by affinity purification with streptavidin-agarose, S-thiolated proteins were purified from CHAPS-soluble kidney homogenate. The proteins were then separated by SDS-PAGE and stained with Coomassie blue. With a combination of matrix-assisted laser desorption ionization time of flight mass spectrometry and LC/MS/MS analysis of protein bands digested with trypsin, a number of S-thiolation substrates were identified. These included the LDL receptor–related protein 2, ATP synthase α chain, heat shock protein 90 β, hydroxyacid oxidase 3, serum albumin precursor, triose phosphate isomerase, and lamin. These represent proteins that may be functionally regulated by S-thiolation and thus could undergo a change in activity or function after renal ischemia and reperfusion. E-mail: [email protected]
Comparing GFR Estimating Equations Using Cystatin C and Creatinine in Elderly Individuals
Authors: Li Fan, Andrew S. Levey, Vilmundur Gudnason, Gudny Eiriksdottir, Margret B. Andresdottir, Hrefna Gudmundsdottir, Olafur S. Indridason, Runolfur Palsson, Gary Mitchell, Lesley A. Inker
Journal: Journal of the American Society of Nephrology (2014)

Current guidelines recommend reporting eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations unless other equations are more accurate, and recommend the combination of creatinine and cystatin C (eGFRcr-cys) as more accurate than either eGFRcr or eGFRcys alone. However, preferred equations and filtration markers in elderly individuals are debated. In 805 adults enrolled in the community-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we measured GFR (mGFR) using plasma clearance of iohexol, standardized creatinine and cystatin C, and eGFR using the CKD-EPI, Japanese, Berlin Initiative Study (BIS), and Caucasian and Asian pediatric and adult subjects (CAPA) equations. We evaluated equation performance using bias, precision, and two measures of accuracy. We first compared the Japanese, BIS, and CAPA equations with the CKD-EPI equations to determine the preferred equations, and then compared eGFRcr and eGFRcys with eGFRcr-cys using the preferred equations. Mean (SD) age was 80.3 (4.0) years. Median (25th, 75th) mGFR was 64 (52, 73) ml/min per 1.73 m 2 , and the prevalence of decreased GFR was 39% (95% confidence interval, 35.8 to 42.5). Among 24 comparisons with the other equations, CKD-EPI equations performed better in 9, similar in 13, and worse in 2. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr in four metrics, better than eGFRcys in two metrics, and similar to eGFRcys in two metrics. In conclusion, neither the Japanese, BIS, nor CAPA equations were superior to the CKD-EPI equations in this cohort of community-dwelling elderly individuals. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr or eGFRcys.
Peripheral tolerance to alloantigen results from altered regulation of the interleukin 2 pathway.
Authors: M J Dallman, O Shiho, T H Page, K J Wood, P J Morris
Journal: The Journal of Experimental Medicine (1991)

Tolerance to alloantigen may be induced in rats by administration of blood followed by transplantation of a renal allograft. The mechanism of this tolerance was investigated by directly analyzing the functional activity of graft-infiltrating cells. We have previously shown cytotoxic T lymphocyte infiltration of, and major histocompatibility complex induction on, grafts of tolerant animals. We now report that cells isolated from the grafts of tolerant rats show a reduced expression of the p55 interleukin 2 receptor (IL-2R) chain on the cell surface compared with that seen on the cells of untreated animals. Scatchard analysis further reveals low expression of high affinity IL-2R. This is due to reduced transcription of both IL-2R alpha and beta chain mRNAs and results in a reduced ability of cells to proliferate in response to IL-2. Cells isolated from tolerant animals are unable to make biologically active IL-2 in culture, whereas cells from untreated animals make high levels. This is not reflected at the mRNA level as the IL-2 gene is induced in both tolerant and untreated animals to similar levels. The induction of tolerance is abrogated by administration of recombinant IL-2 to animals at the time of transplantation. Thus, we conclude that an altered regulation of the IL-2 pathway results in tolerance in these alloantigen-treated and transplanted animals.
Prescribing and guidelines: both must improve to combat antimicrobial resistance
Authors: M. Thomas, D.B. Price, A. Chisholm
Journal: European Respiratory Journal (2012)

To the Editors:

In a recent European Respiratory Journal editorial, Woodhead [1] provided an interesting examination of the contribution of inappropriate antibiotic prescribing for lower respiratory tract infections (LRTIs) in the community to the development and spread of antimicrobial resistance in common bacterial pathogens.

The discussion reports that the heterogeneous antibiotic prescribing across Europe seen in the GRACE (Genomics to Combat Resistance against Antibiotics in Community-acquired LRTI in Europe) network data was associated with no clinically important outcome differences. Yet Woodhead [1] goes on to note that other research, …
Influence of the Menstrual Cycle on Sympathetic Activity, Baroreflex Sensitivity, and Vascular Transduction in Young Women
Authors: Christopher T. Minson, John R. Halliwill, Tamica M. Young, Michael J. Joyner
Journal: Circulation (2000)

Background —Our goal was to test sympathetic and cardiovagal baroreflex sensitivity and the transduction of sympathetic traffic into vascular resistance during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle. Methods and Results —Sympathetic baroreflex sensitivity was assessed by lowering and raising blood pressure with intravenous bolus doses of sodium nitroprusside and phenylephrine. It was defined as the slope relating muscle sympathetic nerve activity (MSNA; determined by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. Vascular transduction was evaluated during ischemic handgrip exercise and postexercise ischemia, and it was defined as the slope relating MSNA and calf vascular resistance (determined by plethysmography). Resting MSNA (EF, 1170±151 U/min; ML, 2252±251 U/min; P &lt;0.001) and plasma norepinephrine levels (EF, 240±21 pg/mL; ML, 294±25 pg/mL; P =0.025) were significantly higher in the ML than in the EF phase. Furthermore, sympathetic baroreflex sensitivity was greater during the ML than the EF phase in every subject (MSNA/diastolic blood pressure slopes: EF, −4.15; FL, −5.42; P =0.005). No significant differences in cardiovagal baroreflex sensitivity or vascular transduction were observed. Conclusions —The present study suggests that the hormonal fluctuations that occur during the normal menstrual cycle may alter sympathetic outflow but not the transduction of sympathetic activity into vascular resistance.
Probucol in the treatment of non-alcoholic steatohepatitis: a double-blind randomized controlled study
Authors: Shahin Merat, Reza Malekzadeh, Masoud Reza Sohrabi, Masoud Sotoudeh, Nasser Rakhshani, Amir Ali Sohrabpour, Siavosh Naserimoghadam
Journal: Journal of Hepatology (2003)
Letter by Safar and Jankowski Regarding Article, “Arterial Stiffness and Cardiovascular Events: The Framingham Heart Study”
Authors: Michel E. Safar, Piotr Jankowski
Journal: Circulation (2010)

We read the article by Mitchell et al 1 with great interest.The authors found that pulse-wave velocity but not central pulse pressure (PP) is independently related to the risk of cardiovascular events in community-based sample.Unexpectedly, PP was not related to the risk of cardiovascular events at all.It is well known that the height of PP is a better predictor of atherosclerosis-related events compared with heart failure-related complications.Indeed, some studies showed even an inverse relationship between PP and mortality in heart failure patients.About 38% of all analyzed events in the study of Mitchell et al were episodes of heart failure.3][4][5] Mitchell et al provided the hazard ratio for pulse-wave velocity after the exclusion of heart failure events.Is it possible to do the same with central PP and PP amplification?The presentation of hazard ratios of peripheral blood pressure would be of special value.This information would allow better assessment of the predictive value of central blood pressure compared with peripheral pressure in the group studied by Mitchell et al.
Expanded Newborn Screening: Implications for Genomic Medicine
Authors: Linda L. McCabe, Edward R.B. McCabe
Journal: Annual Review of Medicine (2008)

Newborn screening (NBS) represents the largest volume of genetic testing. The 45-year history of NBS has demonstrated its benefits, as well as the importance of an evidence base. The recent addition of tandem mass spectrometry (MS/MS) resulted in a fivefold increase in the number of tests. Experience with MS/MS also showed that laboratory tests are just one part of the NBS system. The lessons learned from NBS will provide important insights as we move into the predictive, preventive, and personalized era of genomic medicine.
Inhalation of a prostacyclin analog (iloprost) does not improve exercise capacity in COPD with disproportional pulmonary hypertension
Authors: Lucas Boeck, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2011)

Background:  Pulmonary hypertension (PH) is a common complication of COPD. Although it is likely that cardiovascular factors limit exercise capacity in patients with disproportional PH, most systemic pulmonary vasodilators failed to show any benefit in COPD. The objective of this trial was to investigate whether inhaled iloprost improves exercise capacity in COPD patients with disproportional PH.   Methods:  We performed a randomized, controlled, double-blind, cross-over trial including 19 COPD patients with disproportional PH. Each patient was randomly allocated to nebulized placebo, iloprost 10ug and iloprost 20ug (Multisonic® Infracontrol) before performing a 6MWT at three different time-points. The primary endpoint was the change in walking distance, secondary end-points included exercise test variables. Data were analyzed using mixed-effect models.   Results:  Patients had a mean age of 73.2 years±6.7 and FEV1% pred of 51.6%±30.0. The mPAP was 49.2 mmHg±9.3 during exercise. Three patients had severe side-effects, precluding study continuation. The walking distance was not significantly affected by treatment (mean Δ [95% CI] -12.4m [-32.7 to -7.9],p=0.22). Neither the lowest SaO2 (-0.94% [-2.69 to - 0.82], p=0.28) nor the perceived exertion on BORG scale (0.12 [-0.58 to 0.82], p=0.73) differed among the groups. However, VO2 max (-76.9 mL/min [-122,1 to -31.6], p=0.002) and the maximal minute ventilation (-2.99 L/min [-4.5 to -1.5], p   Conclusions:  Iloprost inhalation does not improve exercise capacity in patients with COPD and disproportional pulmonary hypertension.
Computed tomography and monitoring of emphysema
Authors: H. O. Coxson
Journal: European Respiratory Journal (2007)

It is well known that there have been no successful therapeutic interventions for subjects with emphysema. In the 1990s, investigators became very interested in lung volume reduction surgery (LVRS), first described by Brantigan and Mueller 1 in 1957, as a treatment for severe emphysema. While many sites promoted the use of LVRS for severe emphysema the criteria for the selection of patients, the effects on mortality and the magnitude and durability of benefits were not well established 2. It was for these reasons that the National Emphysema Treatment Trial (NETT) was formed in the USA. While the first report from this study was bleak and warned that subjects who have a low forced expiratory volume in one second and either homogeneous emphysema or a very low diffusing capacity of the lung for carbon monoxide ( D L,CO) had a high risk of dying after this procedure 3, the end results of the study did show that in a select population (upper-lobe patients with low exercise capacity) there was a benefit 2, which persisted for several years 4. The investigators concluded that the effects of LVRS are durable, that it can be recommended for upper-lobe-predominant emphysema patients with low exercise capacity and that it should be considered for palliation in patients with upper-lobe emphysema and high exercise capacity 4. One of the key factors in the outcome of these studies was the location of the emphysema, as described using computed tomography (CT).

CT has become the imaging device of choice for organs such as the lung as it provides physicians with an image of the lung which is very similar to that seen using gross pathology. The removal of overlapping structures commonly seen in standard chest radiography and the relatively good spatial resolution, particularly using the modern …
Chemokine Markers Predict Biochemical Recurrence of Prostate Cancer following Prostatectomy
Authors: David L. Blum, Tatsuki Koyama, Amosy E. M'Koma, Juan M. Iturregui, Magaly Martinez-Ferrer, Consolate Uwamariya, Joseph A. Smith, Peter E. Clark, Neil A. Bhowmick
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Stratifying patients who have a high risk of prostate cancer recurrence following prostatectomy can potentiate the use of adjuvant therapy at an early stage. Inflammation has emerged as a mediator of prostate cancer metastatic progression. We hypothesized that chemokines can be biomarkers for distinguishing patients with high risk for biochemical recurrence of prostate cancer. Experimental Design: In a nested case-control study, 82 subjects developed biochemical recurrence within 5 years of prostatectomy. Prostate tissues from 98 age-matched subjects who were recurrence-free following prostatectomy in the same period were the controls. A high-throughput lectin-based enrichment of prostate tissue enabled multiplex ELISA to identify the expression of three chemokines to discriminate the two patient populations. Results: The expression of CX3CL1 and IL-15 in prostate tissue was associated with 5-year biochemical recurrence-free survival following prostatectomy. However, the expression of chemokine ligand 4 (CCL4) was associated with biochemical recurrence. Multivariable logistic regression model combining preoperative prostate-specific antigen, Gleason score, surgical margin, and seminal vesicle status with the three chemokines doubled the specificity of prediction at 90% sensitivity compared with use of the clinicopathologic variables alone (P &amp;lt; 0.0001). Survival analysis yielded a nomogram that supported the use of CX3CL1, IL-15, and CCL4 in predicting 1-, 3-, and 5-year recurrence-free survival after prostatectomy. Conclusions: Each of the three chemokines can serve as independent predictors of biochemical recurrence. However, the combination of chemokine biomarkers plus clinicopathologic variables discriminated prostatectomy subjects for the probability of biochemical recurrence significantly better than clinicopathologic variables alone.
Cancer Patients'Willingness to Use It for Their Health
Authors: A. Girault, M. Ferrua, A. Fourcade, G. Hébert, C. Sicotte, M. Mons, S. Beaupère, N. Mezaour, F. Lemare, A. Montaron, M.P. Ducreux, C. Guepratte, M. Di Palma, E. Minvielle
Journal: Annals of Oncology (2014)
A Single Treatment of Yttrium-90-labeled CHX-A″–C6.5 Diabody Inhibits the Growth of Established Human Tumor Xenografts in Immunodeficient Mice
Authors: Gregory P. Adams, Calvin C. Shaller, Ekaterina Dadachova, Heidi H. Simmons, Eva M. Horak, Abohawariat Tesfaye, Andres J. P. Klein-Szanto, James D. Marks, Martin W. Brechbiel, Louis M. Weiner
Journal: Cancer Research (2004)

Antitumor diabody molecules are noncovalent single-chain Fv dimers that recapitulate the divalent binding properties of native IgG antibodies. Diabodies are capable of substantial accumulation in tumor xenografts expressing relevant antigens in immunodeficient mouse models. With a Mr of approximately 55,000, diabodies are rapidly cleared from the circulation, resulting in tumor-to-blood ratios that significantly exceed those achieved early after the administration of monoclonal antibodies. We have evaluated the therapeutic potential of the beta-emitting isotope yttrium-90 (t1/2, 64 hours) conjugated to the C6.5K-A diabody that specifically targets the HER2/neu human tumor-associated antigen. We have found that a single intravenous dose of 150 microCi (200 microg) 90Y-CHX-A"-C6.5K-A diabody substantially inhibits the growth rates of established MDA-361/DYT2 human breast tumor xenografts in athymic nude mice. In contrast, 300 microCi (300 microg) 90Y-CHX-A"-C6.5K-A diabody resulted in only a minor delay in the growth of SK-OV-3 human ovarian cancer xenografts. The maximum tolerated dose was also dependent on the tumor xenograft model used. These studies indicate that genetically engineered antitumor diabody molecules can be used as effective vehicles for radioimmunotherapy.
Dissolution of calcium pyrophosphate crystals by polyphosphates: an in vitro and ex vivo study
Authors: R Cini, D Chindamo, M Catenaccio, S Lorenzini, E Selvi, F Nerucci, M P Picchi, G Berti, R Marcolongo
Journal: Annals of the Rheumatic Diseases (2001)

To determine the dissolving ability (DA) of linear pentasodium tripolyphosphate (PSTP), cyclic trisodium metaphosphate (TSMP), polymeric sodium metaphosphate (SMP) on synthetic crystals of calcium pyrophosphate dihydrate (CPPD) and on crystalline aggregates of menisci from patients with chondrocalcinosis (CC).Synthetic CPPD crystals were mixed with phosphate buffered saline (PBS), which contained the different polyphosphates, for one hour at 37 degrees C. The calcified menisci were obtained from the knees of four female patients with CPPD disease who underwent total arthroscopic meniscectomy for degenerative meniscal lesions. Meniscal cryosections and fragments were incubated in SMP (15 mg/ml PBS) at 37 degrees C for one hour and 24 hours, respectively. Histological evaluation on meniscal samples after polyphosphate incubation was carried out by ordinary transmitted light microscopy and polarised light microscopy. The dissolution of CPPD crystals by polyphosphates was assessed by atomic absorption spectroscopy, which determined the amount of calcium liberated from synthetic crystals and meniscal fragments. Cytotoxicity of SMP was evaluated by tetrazolium salt assay and by an ultrastructural study on cultured chondrocytes.SMP and PSTP showed higher DA on CPPD crystals than TSMP. Analysis of the DA values at increasing concentrations of SMP showed that a concentration of 15 mg/ml completely dissolved 2.0 mg CPPD crystals. The solution of meniscal CPPD crystals showed a significant increase of calcium concentration after three hours and 24 hours of SMP incubation (p=0.0001; Kruskal-Wallis analysis of variance) compared with fragments incubated in PBS control solution. Macroscopic and microscopic evaluation of meniscal specimens showed a notable reduction of CPPD deposits. A 50% inhibitory dose on cultured chondrocytes was reached at the maximum concentration of SMP used in this work (15 mg/ml); ultrastructural analysis did not show morphological alterations in the treated cells.The results of this study indicate that linear polyphosphates are effective in dissolving both synthetic and ex vivo CPPD crystal aggregates. This suggests a potential therapeutic use for these molecules in the treatment of symptomatic CC.
International group reiterates stance against human organ trafficking
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

The buying and selling of organs, especially kidneys, from living donors who are not related to the recipient is increasing, but the Transplantation Society, the only international organisation concerned with transplantation, last week reiterated its opposition to the practice.

About 65 000 transplant operations are done each year worldwide, of which about 45 000 are kidney transplantations. Many, if not most, transplants are from living donors, says the society, which has 3000 members from about 70 countries.

To …
Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention
Authors: Goran Bjelakovic, Dimitrinka Nikolova, Lise Lotte Gluud, Rosa G. Simonetti, Christian Gluud
Journal: JAMA (2007)

<h3>Context</h3> Antioxidant supplements are used for prevention of several diseases. <h3>Objective</h3> To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials. <h3>Data Sources and Trial Selection</h3> We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials. <h3>Data Extraction</h3> We included 68 randomized trials with 232 606 participants (385 publications). <h3>Data Synthesis</h3> When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality. <h3>Conclusions</h3> Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.