tbuckley/cabot-search huggingface dataset:
Perioperative Mortality and Long-term Survival Following Live Kidney Donation
Authors: Dorry L. Segev
Journal: JAMA (2010)

More than 6000 healthy US individuals every year undergo nephrectomy for the purposes of live donation; however, safety remains in question because longitudinal outcome studies have occurred at single centers with limited generalizability.To study national trends in live kidney donor selection and outcome, to estimate short-term operative risk in various strata of live donors, and to compare long-term death rates with a matched cohort of nondonors who are as similar to the donor cohort as possible and as free as possible from contraindications to live donation.Live donors were drawn from a mandated national registry of 80 347 live kidney donors in the United States between April 1, 1994, and March 31, 2009. Median (interquartile range) follow-up was 6.3 (3.2-9.8) years. A matched cohort was drawn from 9364 participants of the third National Health and Nutrition Examination Survey (NHANES III) after excluding those with contraindications to kidney donation.Surgical mortality and long-term survival.There were 25 deaths within 90 days of live kidney donation during the study period. Surgical mortality from live kidney donation was 3.1 per 10,000 donors (95% confidence interval [CI], 2.0-4.6) and did not change during the last 15 years despite differences in practice and selection. Surgical mortality was higher in men than in women (5.1 vs 1.7 per 10,000 donors; risk ratio [RR], 3.0; 95% CI, 1.3-6.9; P = .007), in black vs white and Hispanic individuals (7.6 vs 2.6 and 2.0 per 10,000 donors; RR, 3.1; 95% CI, 1.3-7.1; P = .01), and in donors with hypertension vs without hypertension (36.7 vs 1.3 per 10,000 donors; RR, 27.4; 95% CI, 5.0-149.5; P < .001). However, long-term risk of death was no higher for live donors than for age- and comorbidity-matched NHANES III participants for all patients and also stratified by age, sex, and race.Among a cohort of live kidney donors compared with a healthy matched cohort, the mortality rate was not significantly increased after a median of 6.3 years.
α-Tocopherol Supplementation Decreases Plasminogen Activator Inhibitor-1 and P-Selectin Levels in Type 2 Diabetic Patients
Authors: Sridevi Devaraj, Alberto V. Cabo Chan, Ishwarlal Jialal
Journal: Diabetes Care (2002)

OBJECTIVE—Type 2 diabetic subjects have an increased propensity to premature atherothrombosis. α-Tocopherol (AT), a potent antioxidant, has anti-inflammatory properties at high doses. The aim of the study was to test the effect of natural (RRR)-AT supplementation (1,200 IU/day) on markers of thrombosis, plasminogen activator inhibitor-1 (PAI-1), and soluble P-selectin (sP-selectin) in type 2 diabetic patients with and without macrovascular complications (MVCs) compared with matched control subjects. RESEARCH DESIGN AND METHODS—The volunteers comprised type 2 diabetic patients with (n=23) and without (n=24) MVCs and matched control subjects (n=25). Plasma levels of PAI-1 and P-selectin were assayed at baseline, after 3 months of supplementation, and after a 2-month washout phase. RESULTS—Both diabetic groups had significantly increased levels of PAI-1 compared with control subjects (P &amp;lt; 0.025), whereas only type 2 diabetic patients with MVCs had significantly elevated levels of sP-selectin compared with control subjects. AT supplementation significantly lowered levels of PAI-1 and sP-selectin in all three groups. The reduction in PAI-1 levels with AT supplementation was significantly greater in type 2 diabetic patients with MVCs than in those without MVCs (P=0.005). CONCLUSIONS—Thus, AT therapy decreases markers of thrombosis in diabetic patients and control subjects and could be an adjunctive therapy in the prevention of atherosclerosis.
Molecular Classification and Survival Prediction in Human Gliomas Based on Proteome Analysis
Authors: Yasuo Iwadate, Tsukasa Sakaida, Takaki Hiwasa, Yuichiro Nagai, Hiroshi Ishikura, Masaki Takiguchi, Akira Yamaura
Journal: Cancer Research (2004)

Abstract The biological features of gliomas, which are characterized by highly heterogeneous biological aggressiveness even in the same histological category, would be precisely described by global gene expression data at the protein level. We investigated whether proteome analysis based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry can identify differences in protein expression between high- and low-grade glioma tissues. Proteome profiling patterns were compared in 85 tissue samples: 52 glioblastoma multiforme, 13 anaplastic astrocytomas, 10 atrocytomas, and 10 normal brain tissues. We could completely distinguish the normal brain tissues from glioma tissues by cluster analysis based on the proteome profiling patterns. Proteome-based clustering significantly correlated with the patient survival, and we could identify a biologically distinct subset of astrocytomas with aggressive nature. Discriminant analysis extracted a set of 37 proteins differentially expressed based on histological grading. Among them, many of the proteins that were increased in high-grade gliomas were categorized as signal transduction proteins, including small G-proteins. Immunohistochemical analysis confirmed the expression of identified proteins in glioma tissues. The present study shows that proteome analysis is useful to develop a novel system for the prediction of biological aggressiveness of gliomas. The proteins identified here could be novel biomarkers for survival prediction and rational targets for antiglioma therapy.
T-bet–dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow
Authors: Craig N. Jenne, Anselm Enders, Richard Rivera, Susan R. Watson, Alexander J. Bankovich, Joao P. Pereira, Ying Xu, Carla M. Roots, Joshua N. Beilke, Arnob Banerjee, Steven L. Reiner, Sara A. Miller, Amy S. Weinmann, Chris C. Goodnow, Lewis L. Lanier, Jason G. Cyster, Jerold Chun
Journal: The Journal of Experimental Medicine (2009)

During a screen for ethylnitrosourea-induced mutations in mice affecting blood natural killer (NK) cells, we identified a strain, designated Duane, in which NK cells were reduced in blood and spleen but increased in lymph nodes (LNs) and bone marrow (BM). The accumulation of NK cells in LNs reflected a decreased ability to exit into lymph. This strain carries a point mutation within Tbx21 (T-bet), which generates a defective protein. Duane NK cells have a 30-fold deficiency in sphingosine-1-phosphate receptor 5 (S1P5) transcript levels, and S1P5-deficient mice exhibit an egress defect similar to Duane. Chromatin immunoprecipitation confirms binding of T-bet to the S1pr5 locus. S1P-deficient mice exhibit a more severe NK cell egress block, and the FTY720-sensitive S1P1 also plays a role in NK cell egress from LNs. S1P5 is not inhibited by CD69, a property that may facilitate trafficking of activated NK cells to effector sites. Finally, the accumulation of NK cells within BM of S1P-deficient mice was associated with reduced numbers in BM sinusoids, suggesting a role for S1P in BM egress. In summary, these findings identify S1P5 as a T-bet-induced gene that is required for NK cell egress from LNs and BM.
For Debate: Public health 2020
Authors: S J Watkins
Journal: BMJ (1994)

The aim of public health is to improve the health of people in communities and in populations (protection from environmental hazards and provision for health needs). The challenge for public health doctors is to re-establish public health leadership of communities, address social and environmental causes of ill health, and link with primary care (a) to improve the health of neighbourhoods and (b) to combine perspectives in commissioning services. Current threats derive from organisational philosophies. For example, focusing on market development does not allow for population based functions and so neglects the main influences on health. The way forward is a network model of organisation in which small teams collaborate with each other to the common good. For example, successful commissioning authorities would have the public health leadership of the director of public health and the support of the chief executive, treasurer, and representatives of primary care, including a medical adviser from the family health services authority.
Histone Deacetylase Inhibitor Sodium Butyrate Enhances the Cell Killing Effect of Psoralen plus UVA by Attenuating Nucleotide Excision Repair
Authors: Tatsushi Toyooka, Yuko Ibuki
Journal: Cancer Research (2009)

The use of histone deacetylase inhibitors (HDACI), a promising new class of antineoplastic agents, in combination with cytotoxic agents, such as ionizing radiation and anticancer drugs, has been attracting attention. In this study, we found that sodium butyrate (SB), a widely studied HDACI, remarkably enhanced the cell killing effect of psoralen plus UVA (PUVA) in several cancer cell lines, including skin melanoma. Although a single treatment with PUVA or SB did not greatly affect cell survival, combined treatment with SB and PUVA induced marked apoptosis within 24 hours. The SB-induced augmentation of the cell killing effect was more dramatic in combination with PUVA than with anticancer drugs. The number of double-strand breaks that formed during the repair of PUVA-induced interstrand cross-links (ICL) in chromosomal DNA was significantly reduced in SB-pretreated cells, suggesting that the ability to repair ICL was attenuated by SB. In addition, the incorporation of bromodeoxyuridine and the formation of repair foci of proliferating cell nuclear antigen after PUVA treatment, associated with nucleotide excision repair (NER) in the removal of ICL, were not observed in SB-pretreated cells. Furthermore, the repair kinetics of UV-induced cyclobutane pyrimidine dimers (well-known photolesions repaired by NER) were much slower in SB-pretreated cells than in untreated cells. These results indicated that the enhanced cell killing effect of PUVA by SB was attributable to an attenuated ability to repair DNA and, especially, dysfunctional NER.
Active and Passive Smoking and the Incidence of Asthma in the Black Women’s Health Study
Authors: Patricia F. Coogan, Nelsy Castro-Webb, Jeffrey Yu, George T. O’Connor, Julie R. Palmer, Lynn Rosenberg
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Evidence linking active or passive smoking to the incidence of adult-onset asthma is inconsistent with both positive and inverse associations being reported. Most previous studies of active smoking have not accounted for passive smoke exposure, which may have introduced bias.Objectives: To assess the separate associations of active and passive smoking to the incidence of adult-onset asthma in the U.S. Black Women’s Health Study, a prospective cohort of African American women followed since 1995 with mailed biennial questionnaires.Methods: Active smoking status was reported at baseline and updated on all follow-up questionnaires. Passive smoke exposure during childhood, adolescence, and adulthood was ascertained in 1997. Asthma cases comprised women who reported doctor-diagnosed asthma with concurrent asthma medication use. Cox regression models were used to derive multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for former and current smoking and for passive smoking among nonsmokers compared with a reference category of never active or passive smokers.Measurements and Main Results: Among 46,182 participants followed from 1995 to 2011, 1,523 reported incident asthma. The multivariable HRs for former active smoking, current active smoking, and passive smoking only were, respectively, 1.36 (95% CI, 1.11–1.67), 1.43 (95% CI, 1.15–1.77), and 1.21 (95% CI, 1.00–1.45), compared with never active/passive smoking.Conclusions: In this large population with 16 years of follow-up, active smoking increased the incidence of adult-onset asthma, and passive smoke exposure increased the risk among nonsmokers. Continued efforts to reduce exposure to tobacco smoke may have a beneficial effect on the incidence of adult-onset asthma.
Is sleep disordered breathing associated with increased mortality?
Authors: J. A FLEETHAM
Journal: Thorax (1998)

There is a continuum in sleep disordered breathing (SDB) from chronic snoring to upper airway resistance syndrome to obstructive sleep apnoea (OSA) that is associated with progressively increasing consequences. The reported prevalence of SDB depends on the recognition threshold. In a landmark community based study, Young and coworkers1 found that 2% of women and 4% of men had both daytime sleepiness and an apnoea-hypopnoea index (AHI) of >5/hour. In this month’s Thorax Knuistingh Neven and colleagues2 present data from a small Dutch town which suggest that the prevalence of OSA with associated daytime sleepiness is at least 0.9% in men of 35 years or older. Thus, SDB is common, but how clinically significant is it? In their provocative systematic review Wright et al 3 concluded that there is limited evidence of increased mortality or morbidity in patients with OSA. To put these conclusions in context, it needs to be recognised that our understanding of SDB has only recently moved from its infancy to its adolescence. We are only at a similar stage in our knowledge of the natural …
Short RNA half-lives in the slow-growing marine cyanobacterium Prochlorococcus
Authors: Claudia Steglich, Debbie Lindell, Matthias Futschik, Trent Rector, Robert Steen, Sallie W Chisholm
Journal: Genome biology (2010)

RNA turnover plays an important role in the gene regulation of microorganisms and influences their speed of acclimation to environmental changes. We investigated whole-genome RNA stability of Prochlorococcus, a relatively slow-growing marine cyanobacterium doubling approximately once a day, which is extremely abundant in the oceans. Using a combination of microarrays, quantitative RT-PCR and a new fitting method for determining RNA decay rates, we found a median half-life of 2.4 minutes and a median decay rate of 2.6 minutes for expressed genes - twofold faster than that reported for any organism. The shortest transcript half-life (33 seconds) was for a gene of unknown function, while some of the longest (approximately 18 minutes) were for genes with high transcript levels. Genes organized in operons displayed intriguing mRNA decay patterns, such as increased stability, and delayed onset of decay with greater distance from the transcriptional start site. The same phenomenon was observed on a single probe resolution for genes greater than 2 kb. We hypothesize that the fast turnover relative to the slow generation time in Prochlorococcus may enable a swift response to environmental changes through rapid recycling of nucleotides, which could be advantageous in nutrient poor oceans. Our growing understanding of RNA half-lives will help us interpret the growing bank of metatranscriptomic studies of wild populations of Prochlorococcus. The surprisingly complex decay patterns of large transcripts reported here, and the method developed to describe them, will open new avenues for the investigation and understanding of RNA decay for all organisms.
Neutrophil function in pregnancy and rheumatoid arthritis
Authors: I P Crocker
Journal: Annals of the Rheumatic Diseases (2000)

Pregnancy exerts suppressive effects on rheumatoid arthritis (RA). An attenuation in neutrophil function in late pregnancy which may explain this amelioration has previously been reported.A longitudinal investigation of neutrophil activity in healthy pregnant women (n=9) and pregnant patients with RA (n=9), compared with age matched non-pregnant patients with RA (n=12) and healthy controls (n=22).Neutrophil activation was measured in response to the physiological receptor agonists, n-formyl-methionyl-leucyl-phenylalanine (fMLP) and zymosan activated serum (ZAS). Superoxide anion production (respiratory burst) was determined by lucigenin enhanced chemiluminescence (LUCL); secondary granule lactoferrin release by enzyme linked immunosorbent assay (ELISA); and CD11b, CD18, and CD62L expression by flow cytometric analysis.Stimulated neutrophil LUCL was significantly reduced in both pregnant women with RA and healthy pregnant women in the second (fMLP 43% and 69%, ZAS 43% and 59%, respectively) and third trimesters (fMLP 24% and 44%, ZAS 32% and 38%, respectively). Responses returned to normal within eight weeks of delivery and unstimulated levels remained unchanged throughout pregnancy. Basal and stimulated CD11b, CD18, and CD62L expression showed no variations throughout gestation for both pregnancy groups. Likewise, stimulated lactoferrin release and plasma lactoferrin remained unchanged. Certain morphological differences in RA neutrophils were highlighted by the flow cytometric analysis. Moreover, resting neutrophils and stimulated cells from patients with RA, including pregnant subjects, showed a marked increase in LUCL, but a reduction in CD11b, CD18, and CD62L. Low dose prednisolone and methylprednisolone had no effect on neutrophil parameters over the period of treatment with non-steroidal anti-inflammatory drugs.The attenuation to neutrophil respiratory burst in both healthy and RA pregnancies may offer an explanation for the pregnancy induced remission of this inflammatory disorder.
Adjuvant Chemotherapy With Fluorouracil Plus Folinic Acid vs Gemcitabine Following Pancreatic Cancer Resection
Authors: John P. Neoptolemos, Deborah D. Stocken, Claudio Bassi, Paula Ghaneh, David Cunningham, David Goldstein, Robert Padbury, Malcolm J. Moore, Steven Gallinger, Christophe Mariette, Moritz N. Wente, Jakob R. Izbicki, Helmut Friess, Markus M. Lerch, Christos Dervenis, Attila Oláh, Giovanni Butturini, Ryuichiro Doi, Pehr A. Lind, David Smith, Juan W. Valle, Daniel H. Palmer, John A. Buckels, Joyce Thompson, Colin J. McKay, Charlotte L. Rawcliffe, Markus W. Büchler, for the European Study Group for Pancreatic Cancer
Journal: JAMA (2010)

Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer.To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer.The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up.Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m(2), intravenous bolus injection, followed by fluorouracil, 425 mg/m(2) intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m(2) intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months.Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life.Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (chi(1)(2) = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups.Compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer.clinicaltrials.gov Identifier: NCT00058201.
Abstract 20520: A New Lysosome-Mediated Degradation Mechanism for Hepatic Lipid Droplets Turnover
Authors: Mohsen Amir Alipour, Meenakshi Sundaram, Zemin Yao
Journal: Circulation (2014)

Dietary supplementation with fish oil, rich in n-3 fatty acids such as EPA (20:5n-3), has been shown in many studies to exert a hypotriglyceridemic effect by reducing both plasma triglycerides (in the form of VLDL) and intrahepatic triglycerides (presented in cytoplasm as lipid droplets). To date, no cellular or molecular mechanisms have been defined to explain the hypotriglyceridemic action of n-3 fatty acids. Intrahepatocellular triglycerides are an important contributor to plasma fatty acids and lipoproteins level. We have discovered a direct interaction between lysosome and lipid droplets, in a Kiss-and-run fashion, as the principal mechanism for the lipid droplets turnover upon EPA treatment. Inactivating lysosome function or disrupting lysosome movement resulted in accumulation of lipid droplets under EPA treatment conditions, whereas inactivating the known lipolysis enzymes ATGL or HSL was unable to attenuate droplets turnover. Lipophagy has been reported as a selective autophagic mechanism for degradation of lipid droplets under starvation conditions. However, knockdown of autophagy proteins did not prevent droplets turnover induced by EPA. On the other hand, silencing lysosome-associated GTPase Rab7 or the Rab7 effectors, such as FYCO1 and RILP, entirely blocked EPA-induced droplets turnover. Overexpression of the lysosome-associated Arf-like GTPase Arl8b markedly accelerated the EPA-induced droplets turnover. The current study thus unveiled a new lysosome-mediated lipid degradation mechanism that is responsible for the hypotriglyceridemia action of n-3 fatty acids. The therapeutic potential for the treatment of non-alcoholic hepatosteatosis will be discussed.
Calicoblastic Neoplasms in <italic>Acropora palmata</italic>, With a Review of Reports on Anomalies of Growth and Form in Corals<xref ref-type="fn" rid="FN1">2</xref>
Authors: E C Peters, J C Halas, H B McCarty
Journal: JNCI Journal of the National Cancer Institute (1986)

Colonies of the elkhorn coral (Acropora palmata), possessing raised, whitened, irregularly shaped skeletal protuberances, were discovered at Carysfort Reef and Grecian Rocks, Key Largo National Marine Sanctuary, Key Largo, FL. These lesions exhibited relatively rapid growth and spread along the branches, as polyps were overlaid by coenosteal skeletal material. Histopathological examinations of the soft tissues surrounding and extending into the skeletal masses revealed proliferation of gastrovascular canals and associated calicoblastic epidermis, with loss of normal polyp structures and zooxanthellae. The slightly atypical tumor calicoblasts were cuboidal to columnar, resembling those found in the rapidly growing apical tips. Stable carbon isotope ratios of skeletal samples revealed that the tumor skeleton was isotopically lighter than the skeleton in the normal or apical track regions, indicative of higher tissue metabolic rates and lack of carbon isotope fractionation by zooxanthellae. This condition appears to be a neoplasm of the coral, and it is proposed that it be classified “calicoblastic epithelioma.” Several different types of abnormal skeletal deposition, possibly the result of neoplastic processes, have been reported to occur in stony corals and are here reviewed.