tbuckley/cabot-search huggingface dataset:
Minimizing hemorrhagic complications in dialysis patients.
Authors: J W Lohr, S J Schwab
Journal: Journal of the American Society of Nephrology (1991)

Renal failure is associated with an increased incidence of hemorrhage from a variety of sites, particularly in patients undergoing surgical procedures. The primary factors in the pathogenesis of bleeding in renal failure are platelet biochemical abnormalities and alterations in platelet vessel wall interactions. Hemodialysis improves hemostatic abnormalities in uremia, but the need for heparinization during the procedure may increase the bleeding risk. The risk of bleeding may be minimized by using peritoneal dialysis or alternative means to routine heparinization to prevent clotting in the extracorporeal circulation during hemodialysis. These include use of minimal heparin, prostacyclin, regional citrate anticoagulation, and no anticoagulation. Continuous arteriovenous hemodialysis may also be performed with regional citrate anticoagulation. There are several nondialytic therapies that may be used to prevent or treat hemorrhage in renal failure patients. These include administration of cryoprecipitate, 1-deamino-8-arginine vasopressin, estrogens, red blood cells, and erythropoietin. A clinical strategy to minimize bleeding complications in dialysis patients is presented.
Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure
Authors: Eiji Ishimura, Yoshiki Nishizawa, Masaaki Inaba, Naoki Matsumoto, Masanori Emoto, Takahiko Kawagishi, Shigeichi Shoji, Senji Okuno, Masao Kim, Takami Miki, Hirotoshi Morii
Journal: Kidney International (1999)
Earlier Onset and Greater Severity of Disordered Mineral Metabolism in Diabetic Patients With Chronic Kidney Disease
Authors: Patricia Wahl, Huiliang Xie, Julia Scialla, Cheryl A.M. Anderson, Keith Bellovich, Carolyn Brecklin, Jing Chen, Harold Feldman, Orlando M. Gutierrez, Jim Lash, Mary B. Leonard, Lavinia Negrea, Sylvia E. Rosas, Amanda Hyre Anderson, Raymond R. Townsend, Myles Wolf, Tamara Isakova
Journal: Diabetes Care (2012)

OBJECTIVE Disordered mineral metabolism is a common complication of chronic kidney disease (CKD) and a novel risk factor for CKD progression, cardiovascular disease, and mortality. Although diabetes is the leading cause of CKD and is associated with worse clinical outcomes than other etiologies, few studies have evaluated mineral metabolism in CKD according to diabetes status. RESEARCH DESIGN AND METHODS Using the Chronic Renal Insufficiency Cohort Study, we tested the hypothesis that diabetes is independently associated with lower serum calcium and higher serum phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23). RESULTS Compared with participants without diabetes (n = 1,936), those with diabetes (n = 1,820) were more likely to have lower estimated glomerular filtration rate (eGFR), lower serum albumin, and higher urinary protein excretion (all P &amp;lt; 0.001). Unadjusted serum phosphate, PTH, and FGF23 levels were higher and calcium was lower among those with compared with those without diabetes (all P &amp;lt; 0.001). After multivariate adjustment, diabetes remained a significant predictor of serum phosphate, PTH, and FGF23 but not calcium. The eGFR cut point at which 50% of participants met criteria for secondary hyperparathyroidism or elevated FGF23 was higher in participants with diabetes compared with those without (PTH: eGFR 30–39 vs. 20–29, P &amp;lt; 0.001; FGF23: eGFR 50–59 vs. 40–49, P &amp;lt; 0.001). CONCLUSIONS Disordered mineral metabolism begins earlier in the course of CKD and is more severe among CKD patients with compared with those without diabetes. Future studies should explore mechanisms for these differences and whether they contribute to excess risks of adverse clinical outcomes among diabetic patients with CKD.
Lung cancer care in UK is still unacceptably variable, says report
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

Despite the fact that fewer people are developing lung cancer, and more are surviving it, access to treatment still varies with age and location in the United Kingdom, a report says.1

The UK Lung Cancer Coalition is a multi-interest group that was set up in 2005 to improve lung cancer outcomes. Its review of the past 10 years says that GP contracts should prioritise early diagnosis of lung cancer and that the Be Clear on Cancer lung cancer awareness campaign needs to …
Identification of Protein-Coding Regions in DNA Sequences Using A Time-Frequency Filtering Approach
Authors: Sitanshu Sekhar Sahu, Ganapati Panda
Journal: Genomics Proteomics & Bioinformatics (2011)

Abstract Accurate identification of protein-coding regions (exons) in DNA sequences has been a challenging task in bioinformatics. Particularly the coding regions have a 3-base periodicity, which forms the basis of all exon identification methods. Many signal processing tools and techniques have been applied successfully for the identification task but still improvement in this direction is needed. In this paper, we have introduced a new promising model-independent time-frequency filtering technique based on S-transform for accurate identification of the coding regions. The S-transform is a powerful linear time-frequency representation useful for filtering in time-frequency domain. The potential of the proposed technique has been assessed through simulation study and the results obtained have been compared with the existing methods using standard datasets. The comparative study demonstrates that the proposed method outperforms its counterparts in identifying the coding regions.
Early evidence of ethnic differences in cardiovascular risk: cross sectional comparison of British South Asian and white children
Authors: P. H Whincup
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To examine whether British South Asian children differ in insulin resistance, adiposity, and cardiovascular risk profile from white children. <b>Design:</b> Cross sectional study. <b>Setting:</b> Primary schools in 10 British towns. <b>Participants:</b> British children aged 8 to 11 years (227 South Asian and 3415 white); 73 South Asian and 1287 white children aged 10 and 11 years provided blood samples (half fasting, half after glucose load). <b>Main outcome measures:</b> Insulin concentrations, anthropometric measures, established cardiovascular risk factors. <b>Results:</b> Mean ponderal index was lower in South Asian children than in white children (mean difference −0.43 kg/m<sup>3</sup>, 95% confidence interval −0.13 kg/m<sup>3</sup> to −0.73 kg/m<sup>3</sup>). Mean waist circumferences and waist:hip ratios were similar. Mean insulin concentrations were higher in South Asian children (percentage difference was 53%, 14% to 106%, after fasting and 54%, 19% to 99%, after glucose load), though glucose concentrations were similar. Mean heart rate and triglyceride and fibrinogen concentrations were higher among South Asian children; serum total, low density lipoprotein, and high density lipoprotein cholesterol concentrations were similar in the two groups. Differences in insulin concentrations remained after adjustment for adiposity and other potential confounders. However, the relations between adiposity and insulin concentrations (particularly fasting insulin) were much stronger among South Asian children than among white children. <b>Conclusions:</b> The tendency to insulin resistance observed in British South Asian adults is apparent in children, in whom it may reflect an increased sensitivity to adiposity. Action to prevent non-insulin dependent diabetes in South Asian adults may need to begin during childhood. <h3>What is already known on this topic</h3> Compared with white people British South Asians are at increased risk of coronary heart disease, stroke, and non-insulin dependent diabetes There is evidence that these conditions originate in early life <h3>What this study adds</h3> British South Asian children show higher average levels of insulin and insulin resistance than white children These ethnic differences in insulin resistance in childhood are not associated with corresponding differences in adiposity, particularly central adiposity Insulin metabolism seems to be more sensitive to a given degree of adiposity among the South Asian children compared with white children The prevention of insulin resistance and its consequences may need to begin during childhood, particularly in South Asians
Gynaecological Abnormalities Found at a Cytology Clinic
Authors: D. Edwards
Journal: BMJ (1974)

A survey was made of abnormalities found on pelvic examination of 2,656 women who attended for cervical smears in the three years 1967-9. Eight women had malignant cells in their smears, and 68 women pelvic tumours, four of them malignant. Severe vulvitis was common in women over 46. Many of the women who had non-malignant conditions were treated though they had no complaints. They were among the most appreciative and subsequently sought out the clinic staff to thank them. It is important that a full examination should be made by an experienced gynaecologist.
Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme.
Authors: D Salvatore, S C Low, M Berry, A L Maia, J W Harney, W Croteau, D L St Germain, P R Larsen
Journal: Journal of Clinical Investigation (1995)

Type 3 iodothyronine deiodinase (D3) catalyzes the conversion of T4 and T3 to inactive metabolites. It is highly expressed in placenta and thus can regulate circulating fetal thyroid hormone concentrations throughout gestation. We have cloned and expressed a 2.1-kb human placental D3 cDNA which encodes a 32-kD protein with a Km of 1.2 nM for 5 deiodination of T3 and 340 nM for 5' deiodination of reverse T3. The reaction requires DTT and is not inhibited by 6n-propylthiouracil. We quantitated transiently expressed D3 by specifically labeling the protein with bromoacetyl [125I]T3. The Kcat/Km ratio for 5 deiodination of T3 was over 1,000-fold that for 5' deiodination of reverse T3. Human D3 is a selenoenzyme as evidenced by (a) the presence of an in frame UGA codon at position 144, (b) the synthesis of a 32-kD 75Se-labeled protein in D3 cDNA transfected cells, and (c) the presence of a selenocysteine insertion sequence element in the 3' untranslated region of the mRNA which is required for its expression. The D3 selenocysteine insertion sequence element is more potent than that in the type 1 deiodinase or glutathione peroxidase gene, suggesting a high priority for selenocysteine incorporation into this enzyme. The conservation of this enzyme from Xenopus laevis tadpoles to humans implies an essential role for regulation of thyroid hormone inactivation during embryological development.
Cutaneous leucocytoclastic vasculitis caused by cyclosporin A (Sandimmun)
Authors: M N GUPTA
Journal: Annals of the Rheumatic Diseases (2000)

Cutaneous leucocytoclastic vasculitis caused by cyclosporin A (Sandimmun)Cutaneous leucocytoclastic vasculitis to cyclosporin A (Sandimmun) has not been previously described.We report the case of a 37 year old man who presented with a 10 day history of a purpuric eruption aVecting both legs.He had been diagnosed as having psoriasis and psoriatic arthropathy 12 years previously, on the basis of joint symptoms, sacroileitis, erosive arthropathy, increased acute phase reactants and positive HLA B27 status.His initial treatments had included oral gold (Auranofin) 3 mg three times per day and salazopyrine 3 g/day.Both were discontinued because of poor control of his joint disease.In July 1997 he was given oral cyclosporin A (Neoral) 50 mg/day, which was increased to 100 mg/day.This was discontinued in January 1998 because of symptoms of fatigue.In April 1998, after further flares of his arthropathy, he was given Sandimmun 50 mg/day by his general practitioner.Within one month of this he developed an acute skin eruption.He was otherwise well and receiving no other medication except indomethacin 150 mg/day, which he had been taking since 1986.On examination, there was a palpable, non-tender, purpuric eruption with necrotising ulceration localised to both lower legs.Routine haematology, biochemistry and urine analysis were normal.Skin biopsy showed a leucocytoclastic vasculitis with heavy dermal neutrophilic infiltrate and few eosinophils (fig 1).Gram stain for organisms was negative.The Sandimmun was discontinued and over a two month period, the purpuric eruption and ulcers healed with residual scarring.
Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation
Authors: Samira Fafi-Kremer, Isabel Fofana, Eric Soulier, Patric Carolla, Philip Meuleman, Geert Leroux-Roels, Arvind H. Patel, François-Loïc Cosset, Patrick Pessaux, Michel Doffoël, Philippe Wolf, Françoise Stoll-Keller, Thomas F. Baumert
Journal: The Journal of Experimental Medicine (2010)

End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive antiviral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to reinfect the liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants reinfecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pretransplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft.
Cigarette smoke extract induces activity of the transposable element LINE1 in primary human lung fibroblasts
Authors: Nicola Miglino, Michael Tamm, Michael Roth, Pieter Borger
Journal: European Respiratory Journal (2013)

Introduction: Cigarette smoke causes cell proliferation disorders, including lung cancer and emphysema. Although approximately 40% of lung cancers are associated with p53 mutations, the major part (60%) is of unknown etiology. Integration of transposable elements (TE) in or nearby cell cycle control genes may disrupt the cell cycle and lead to uncontrolled proliferation. This may lead to loss of lung tissue (emphysema), to hyperplasia or the development of tumors.  Objective: To assess the effect of cigarette smoke extract (CSE) on the expression and transposition of LINE1 (L1), a human TE present in primary human lung fibroblasts. The L1 open reading frame (ORF)-2 protein was detected using immunoblot-analysis (Western). CSE was used as a 1:10 dilution from a solution containing the smoke equivalent of 1 cigarette/25 ml.  Results: Primary fibroblast lines (n=8) were grown in RMPI without and with CSE for 10, 30, 60, 90 and 120 minutes. Resting cells did not express detectable levels of L1-ORF2. CSE induced a biphasic L1-ORF2 expression pattern: an immediate early maximum at 10-30 minutes and a second maximum after 120 minutes. This coincided with a complete inhibition of fibro-proliferation.  Conclusions: CSE induces the expression of L1-ORF2, a marker for TE activity.  Implications: The increased expression of L1-ORF2 implies an overall increased activity of TE, since the L1-transposition machinery is also used by other mobile elements. Uncontrolled transposition of TE may cause gene damage or alteration. The involvement of TE in smoking-induced proliferation-disorders should be envisaged to understand the heterogeneity observed in lung cancers and emphysema.
The Sea and Poison
Authors: R. Basu Roy
Journal: BMJ (2009)

“Doctors aren’t saints.” So says Toda, one of the doctors in Shusaku Endo’s novel that was based on actual human vivisections carried out in Japan during the second world war. “They want to be successful. They want to become full professors. And when they want to try out new techniques, they don’t limit their experiments to monkeys and dogs. Suguro, this is the world, and you ought to take a closer look at it.”

The Sea and Poison is a tale of the subjugation of patients’ care to doctors’ ambitions. It tells of medical error and its concealment and of war crimes carried out by medical staff. A power vacuum …
Phylogenomic Analysis Identifies Red Algal Genes of Endosymbiotic Origin in the Chromalveolates
Authors: Shenglan Li, Tetyana Nosenko, Jeremiah D. Hackett, Debashish Bhattacharya
Journal: Molecular Biology and Evolution (2005)

Endosymbiosis has spread photosynthesis to many branches of the eukaryotic tree; however, the history of photosynthetic organelle (plastid) gain and loss remains controversial. Fortuitously, endosymbiosis may leave a genomic footprint through the transfer of endosymbiont genes to the "host" nucleus (endosymbiotic gene transfer, EGT). EGT can be detected through comparison of host genomes to uncover the history of past plastid acquisitions. Here we focus on a lineage of chlorophyll c-containing algae and protists ("chromalveolates") that are postulated to share a common red algal secondary endosymbiont. This plastid is originally of cyanobacterial origin through primary endosymbiosis and is closely related among the Plantae (i.e., red, green, and glaucophyte algae). To test these ideas, an automated phylogenomics pipeline was used with a novel unigene data set of 5,081 expressed sequence tags (ESTs) from the haptophyte alga Emiliania huxleyi and genome or EST data from other chromalveolates, red algae, plants, animals, fungi, and bacteria. We focused on nuclear-encoded proteins that are targeted to the plastid to express their function because this group of genes is expected to have phylogenies that are relatively easy to interpret. A total of 708 genes were identified in E. huxleyi that had a significant Blast hit to at least one other taxon in our data set. Forty-six of the alignments that were derived from the 708 genes contained at least one other chromalveolate (i.e., besides E. huxleyi), red and/or green algae (or land plants), and one or more cyanobacteria, whereas 15 alignments contained E. huxleyi, one or more other chromalveolates, and only cyanobacteria. Detailed phylogenetic analyses of these data sets turned up 19 cases of EGT that did not contain significant paralogy and had strong bootstrap support at the internal nodes, allowing us to confidently identify the source of the plastid-targeted gene in E. huxleyi. A total of 17 genes originated from the red algal lineage, whereas 2 genes were of green algal origin. Our data demonstrate the existence of multiple red algal genes that are shared among different chromalveolates, suggesting that at least a subset of this group may share a common origin.
Discrimination Between Benign and Malignant Adnexal Masses by Specialist Ultrasound Examination Versus Serum CA-125
Authors: B. Van Calster, D. Timmerman, T. Bourne, A. C. Testa, C. Van Holsbeke, E. Domali, D. Jurkovic, P. Neven, S. Van Huffel, L. Valentin
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundSubjective evaluation of gray-scale and Doppler ultrasound findings (i.e., pattern recognition) by an experienced examiner and preoperative serum levels of CA-125 can both discriminate benign from malignant adnexal (i.e., ovarian, paraovarian, or tubal) masses. We compared the diagnostic performance of these methods in a large multicenter study.
Expression of Transcription Factor E2F1 and Telomerase in Glioblastomas: Mechanistic Linkage and Prognostic Significance
Authors: Marta M. Alonso, Juan Fueyo, Jerry W. Shay, Kenneth D. Aldape, Hong Jiang, Ok-Hee Lee, David G. Johnson, Jing Xu, Yasuko Kondo, Takao Kanzawa, Satoru Kyo, B. Nebiyou Bekele, Xian Zhou, Janice Nigro, J. Matthew McDonald, W. K. Alfred Yung, Candelaria Gomez-Manzano
Journal: JNCI Journal of the National Cancer Institute (2005)

Several tumor suppressor pathways have been identified as modulators of telomerase function. We examined the functional role of the retinoblastoma-E2F1 pathway in regulating telomerase activity in malignant gliomas.Adenovirus vectors were used to transfer cDNAs into human glioblastoma and sarcoma cells. Telomerase activity was assessed with a telomere repeat amplification protocol. Promoter activity in cancer cells was assessed with promoter-luciferase reporter constructs. Promoter binding was assessed with the chromatin immunoprecipitation (ChIP) assay. We isolated astrocytes from E2F1 transgenic mice and normal mice for in vivo studies. We evaluated the expression of E2F1 and hTERT (the catalytic subunit of human telomerase) mRNAs by reverse transcriptase-polymerase chain reaction and proteins in human glioblastoma samples by immunoblot analysis. Associations between survival among 61 glioblastoma multiforme patients and expression of E2F1 and hTERT mRNA and protein were examined with Kaplan-Meier analysis, the log-rank test, and Cox proportional hazards regression models. All statistical tests were two-sided.Ectopic E2F1 expression increased hTERT promoter activity in cancer cells. We detected an interaction between E2F1 protein and the hTERT promoter. Transgenic E2F1 astrocytes contained functional telomerase protein. E2F1 mRNA expression and hTERT mRNA expression were statistically significantly correlated in human glioblastoma specimens (R = .8; P < .001). Longer median survival was statistically significantly associated with lower E2F1 mRNA expression in tumors (103.6 weeks) rather than with higher expression (46.1 weeks) (difference = 57.5 weeks; 95% confidence interval [CI] = 14.7 to 159.7; log-rank P = .002). E2F1 mRNA was the only factor that was statistically significantly associated with overall survival in a multivariable model (P = .04). Among 27 patients with glioblastoma multiforme samples, the expression of E2F1 protein was statistically significantly associated with survival (log-rank P < .001).E2F1 may participate in telomerase activity regulation in malignant glioma cells. Its expression appears to be strongly associated with the survival of patients with malignant brain tumors.