tbuckley/cabot-search huggingface dataset:
Expression of genetically determined diabetes and insulitis in the nonobese diabetic (NOD) mouse at the level of bone marrow-derived cells. Transfer of diabetes and insulitis to nondiabetic (NOD X B10) F1 mice with bone marrow cells from NOD mice.
Authors: L S Wicker, B J Miller, A Chai, M Terada, Y Mullen
Journal: The Journal of Experimental Medicine (1988)

The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is controlled by at least three recessive loci, including one linked to the MHC. To determine whether any of these genetic loci exert their effects via the immune system, radiation bone marrow chimeras were constructed in which (NOD X B10)F1-irradiated recipients were reconstituted with NOD bone marrow cells. Unmanipulated (NOD X B10)F1 mice, or irradiated F1 mice reconstituted with F1 or B10 bone marrow, did not display insulitis or diabetes. In contrast, insulitis was observed in a majority of the NOD----F1 chimeras and diabetes developed in 21% of the mice. These data demonstrate that expression of the diabetic phenotype in the NOD mouse is dependent on NOD-derived hematopoietic stem cells. Diabetogenic genes in the NOD mouse do not appear to function at the level of the insulin-producing beta cells since NOD----F1 chimeras not only developed insulitis and diabetes but also rejected beta cells within pancreas transplants from newborn B10 mice. These data suggest that the beta cells of the NOD mouse do not express a unique antigenic determinant that is the target of the autoimmune response.
Comparison of real-time PCR and nested PCR for the detection of Y chromosome sequences in the peripheral blood mononuclear cells of patients with systemic sclerosis
Authors: M Mosca, T Giuliano, M Curcio, M Doveri, F De Feo, C Tani, L Bazzichi, S Bombardieri
Journal: Annals of the Rheumatic Diseases (2008)

Real-time PCR (RT-PCR) is a sensitive technique that has been recently applied to the determination and quantification of fetomaternal microchimerism.1–3 In a previous manuscript, we detected the presence of Y chromosome sequences in female patients with systemic lupus erythaematosus (SLE) using nested PCR.4 In the present study we evaluated the presence of Y chromosome sequences in the peripheral blood mononuclear cells (PBMCs) of female patients with systemic sclerosis (SSc) using nested and RT-PCR, correlating the results with the clinical and serological manifestations of the patients.

Genomic DNA was isolated from …
Prostate-Specific Antigen Nadir and Cancer-Specific Mortality Following Hormonal Therapy for Prostate-Specific Antigen Failure
Authors: Alexandra J. Stewart, Howard I. Scher, Ming-Hui Chen, David G. McLeod, Peter R. Carroll, Judd W. Moul, Anthony V. D'Amico
Journal: Journal of Clinical Oncology (2005)

For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA), we evaluated whether a PSA nadir of more than 0.2 ng/mL was significantly associated with prostate cancer-specific mortality (PCSM).The study cohort comprised 747 men with rising PSA and negative bone scan after surgery (n = 486) or radiation therapy (n = 261) who were treated with AST. Cox regression was used to evaluate whether a significant association existed between the PSA nadir level after 8 months of AST and the time to PCSM, controlling for treatment and known prognostic factors.The post-AST PSA nadir (pCox < .0001), the pre-AST PSA doubling time (DT) (pCox = .002), PSA level (P = .0001), and Gleason eight to 10 cancers (pCox = .01) were significantly associated with time to PCSM. The adjusted hazard ratio for PCSM was 20 (95% CI, 7 to 61; pCox < .0001), for men with a PSA nadir of more than 0.2 ng/mL as compared with all others. A PSA DT of less than 3 months was observed in 30% (224 of 747) of the study cohort. Of the 28 observed prostate cancer deaths, 21 (75%) occurred in men whose PSA nadir was more than 0.2 ng/mL and who had a PSA DT of less than 3 months.A PSA nadir of more than 0.2 ng/mL after 8 months of AST given for postoperative or postradiation PSA failure is significantly associated with PCSM and is clinically significant because it accounted for 75% of the cancer deaths observed in this study.
Functional Gene Losses Occur with Minimal Size Reduction in the Plastid Genome of the Parasitic Liverwort Aneura mirabilis
Authors: N. J. Wickett, Y. Zhang, S. K. Hansen, J. M. Roper, J. V. Kuehl, S. A. Plock, P. G. Wolf, C. W. dePamphilis, J. L. Boore, B. Goffinet
Journal: Molecular Biology and Evolution (2007)

Aneura mirabilis is a parasitic liverwort that exploits an existing mycorrhizal association between a basidiomycete and a host tree. This unusual liverwort is the only known parasitic seedless land plant with a completely nonphotosynthetic life history. The complete plastid genome of A. mirabilis was sequenced to examine the effect of its nonphotosynthetic life history on plastid genome content. Using a partial genomic fosmid library approach, the genome was sequenced and shown to be 108,007 bp with a structure typical of green plant plastids. Comparisons were made with the plastid genome of Marchantia polymorpha, the only other liverwort plastid sequence available. All ndh genes are either absent or pseudogenes. Five of 15 psb genes are pseudogenes, as are 2 of 6 psa genes and 2 of 6 pet genes. Pseudogenes of cysA, cysT, ccsA, and ycf3 were also detected. The remaining complement of genes present in M. polymorpha is present in the plastid of A. mirabilis with intact open reading frames. All pseudogenes and gene losses co-occur with losses detected in the plastid of the parasitic angiosperm Epifagus virginiana, though the latter has functional gene losses not found in A. mirabilis. The plastid genome sequence of A. mirabilis represents only the second liverwort, and first mycoheterotroph, to have its plastid genome sequenced. We observed a pattern of genome evolution congruent with functional gene losses in parasitic angiosperms but suggest that its plastid genome represents a genome in the early stages of decay following the relaxation of selection pressures.
Effect of Blood and Saline Infusion on Ventricular End Diastolic Pressure, Stroke Work, Stroke Volume and Cardiac Output in the Open and Closed Chest Dog
Authors: THOMAS B. FERGUSON, OSCAR W. SHADLE, DONALD E. GREGG
Journal: Circulation Research (1953)

Left and right ventricular end diastolic pressure, stroke work, stroke volume, and cardiac output were measured in open and closed chest dogs infused with blood and/or saline. The methods employed permitted repeated determinations of these factors during short time intervals. For nonfatigued hearts in the open chest preparation point to point correlation of end diastolic pressure with the other three variables was very good, but in closed chest animals a number of non-correlations occurred. Sufficient variation was seen to indicate that factors other than those measured in this study will have to be known before cardiac performance in the intact animal can be fully assessed.
Viral targeting of hematopoietic progenitors and inhibition of DC maturation as a dual strategy for immune subversion
Authors: Noemí Sevilla, Dorian B McGavern, Chao Teng, Stefan Kunz, Michael B A Oldstone
Journal: Journal of Clinical Investigation (2004)

DCs play a pivotal role in bringing forth innate and adaptive immune responses. Viruses can specifically target DCs, rendering them ineffective in stimulating T cells, which can ultimately lead to immunosuppression. In the present study we have identified several potential mechanisms by which lymphocytic choriomeningitis virus (LCMV) induces immunosuppression in its natural murine host. The immunosuppressive LCMV variant clone 13 (Cl 13) infects DCs and interferes with their maturation and antigen-presenting capacity as evidenced by a significant reduction in the surface expression of MHC class I, MHC class II, CD40, CD80, and CD86 molecules. Additionally, Cl 13 infects hematopoietic progenitor cells both in vivo and in vitro, impairing their development. One mechanism by which hematopoietic progenitors are developmentally impaired is through the Cl 13–induced production of IFN-α and IFN-β (IFN-α/β). Mice deficient in the receptor for IFN-α/β show a normal differentiation of progenitors into DCs despite viral infection. Thus, a virus can evolve a strategy to boost its survival by preventing the maturation of DCs from infected progenitor cells and by reducing the expression of antigen-presenting and costimulatory molecules on developed DCs.
Injury and Repair of Ligaments and Tendons
Authors: Savio L.-Y. Woo, Richard E. Debski, Jennifer Zeminski, Steven D. Abramowitch, Serena S. Chan Saw, MS, James A. Fenwick
Journal: Annual Review of Biomedical Engineering (2000)

In this chapter, biomechanical methods used to analyze healing and repair of ligaments and tendons are initially described such that the tensile properties of these soft tissues as well as their contribution to joint motion can be determined. The focus then turns to the important mechanical and biological factors that improve the healing process of ligaments. The biomechanics of surgical reconstruction of the anterior cruciate ligament and the key surgical parameters that affect the performance of the replacement grafts are subsequently reviewed. Finally, injury mechanisms and the biomechanical analysis of various treatment techniques for various types of tendon injuries are described.
Does the type of vasodilator stress influence defect extent with Tc-99m tetrofosmin SPECT imaging?
Authors: M.R. Mansoor, A.W. Ahlberg, M.G. Levine, C.C. McGrill, G.M. Cyr, A. Russell, D.M. Cross, D. Waters, G.V. Helter
Journal: Journal of the American College of Cardiology (1998)
Guidelines for screening and surveillance of asymptomatic colorectal cancer in patients with inflammatory bowel disease
Authors: J A Eaden, J F Mayberry
Journal: Gut (2002)

Patients with ulcerative colitis (UC) are at increased risk of colorectal carcinoma.1,2 Many clinicians practice colonoscopic surveillance in these patients in the hope of detecting dysplasia or an early cancer at a surgically curable stage. However, a recent audit of gastroenterologists showed such surveillance to be disorganised and inconsistent.3 Much debate surrounds the efficacy and cost effectiveness of surveillance programmes in UC4–6 because they were introduced without benefit of randomised controlled trials.

The following guidelines should bring uniformity to the process and be of help to both surgeons and physicians. The colorectal cancer risk in patients with colonic Crohn’s disease is similar to that in UC7,8 and thus the guidelines for UC should be equally applicable to such patients with Crohn’s disease.



1.  Surveillance colonoscopies should be performed when the disease is in remission. (Recommendation Grade: C). 

2.  All patients should have a screening colonoscopy after 8–10 years that will also clarify disease extent. (Recommendation Grade: C). 

3.  Regular surveillance should begin after 8–10 years (from onset of symptoms) for pancolitis and after 15–20 years for left sided disease. (Recommendation Grade: C).

4.  As the risk of cancer increases exponentially with time, there should be a decrease in the screening interval with increasing disease duration. For patients with pancolitis, in the second decade of disease a colonoscopy should be conducted every three years, every two years in the third decade, and yearly by the fourth decade of disease. (Recommendation Grade: C). 

5.  Two to four random biopsy specimens every 10 cm from the entire colon should be taken with additional samples of suspicious areas. (Recommendation Grade: C).         Patients with primary sclerosing cholangitis (including those with an orthotopic liver transplant) represent a subgroup at higher risk of cancer and they should have annual colonoscopy. (Recommendation Grade: C). 



Although it …
Early mobilisation versus plaster immobilisation of simple elbow dislocations: results of the FuncSiE multicentre randomised clinical trial
Authors: Gijs I T Iordens, Esther M M Van Lieshout, Niels W L Schep, Jeroen De Haan, Wim E Tuinebreijer, Denise Eygendaal, Ed Van Beeck, Peter Patka, Michael H J Verhofstad, Dennis Den Hartog
Journal: British Journal of Sports Medicine (2015)

Background/aim To compare outcome of early mobilisation and plaster immobilisation in patients with a simple elbow dislocation. We hypothesised that early mobilisation would result in earlier functional recovery. Methods From August 2009 to September 2012, 100 adult patients with a simple elbow dislocation were enrolled in this multicentre randomised controlled trial. Patients were randomised to early mobilisation (n=48) or 3 weeks plaster immobilisation (n=52). Primary outcome measure was the Quick Disabilities of the Arm, Shoulder, and Hand ( Quick -DASH) score. Secondary outcomes were the Oxford Elbow Score, Mayo Elbow Performance Index, pain, range of motion, complications and activity resumption. Patients were followed for 1 year. Results Quick -DASH scores at 1 year were 4.0 (95% CI 0.9 to 7.1) points in the early mobilisation group versus 4.2 (95% CI 1.2 to 7.2) in the plaster immobilisation group. At 6 weeks, early mobilised patients reported less disability ( Quick -DASH 12 (95% CI 9 to 15) points vs 19 (95% CI 16 to 22); p&lt;0.05) and had a larger arc of flexion and extension (121° (95% CI 115° to 127°) vs 102° (95% CI 96° to 108°); p&lt;0.05). Patients returned to work sooner after early mobilisation (10 vs 18 days; p=0.020). Complications occurred in 12 patients; this was unrelated to treatment. No recurrent dislocations occurred. Conclusions Early active mobilisation is a safe and effective treatment for simple elbow dislocations. Patients recovered faster and returned to work earlier without increasing the complication rate. No evidence was found supporting treatment benefit at 1 year. Trial registration number NTR 2025.
Treatment with the novel anti-angiogenic agent PI-88 is associated with immune-mediated thrombocytopenia
Authors: M.A. Rosenthal, D. Rischin, G. McArthur, K. Ribbons, B. Chong, J. Fareed, G. Toner, M.D. Green, R.L. Basser
Journal: Annals of Oncology (2002)
Chronic Atrial Fibrillation in Patients With Rheumatic Heart Disease
Authors: Mohan Nair, Prasad Shah, Ravinder Batra, Manoj Kumar, Jagdish Mohan, Upkar Kaul, Ramesh Arora
Journal: Circulation (2001)

Background There is little information concerning mapping and radiofrequency ablation (RFA) of arrhythmias seen during reinduction of atrial fibrillation (AF) after pharmacological and/or electrical cardioversion in patients with chronic AF and rheumatic heart disease. Methods and Results Seventeen patients with rheumatic heart disease and symptomatic chronic AF underwent multisite atrial mapping during reinduction of AF after cardioversion. An organized atrial arrhythmia of varying duration was seen to precede the AF in all patients. The earliest atrial activity during this organized rhythm was near the coronary sinus ostium (CS OS) in 14 patients and along the left side of the interatrial septum (IAS) in 3 patients. RFA was performed in 16 patients (14 near the CS OS and 2 along the IAS). Postablation AF was inducible in 1 patient in whom RFA was preformed near the CS OS and in both patients when it was performed along the IAS. At a follow-up of 6 to 56 weeks (mean, 32 weeks), 10 of the 13 patients who had successful ablation were in sinus rhythm. All patients in whom AF was reinducible immediately after RFA continue to be in AF. Conclusions Induced AF in patients with rheumatic heart disease begins as a rapid organized arrhythmia with earliest atrial activity near the CS OS in most patients. RFA targeting the region of the CS OS is successful in suppressing the arrhythmia immediately in most of the patients and in most on follow-up.
Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial
Authors: Anthony H Barnett, Ambrish Mithal, Jenny Manassie, Russell Jones, Henning Rattunde, Hans J Woerle, Uli C Broedl
Journal: The Lancet Diabetes & Endocrinology (2014)
Two novel mutations and evidence for haploinsufficiency of the <i>ADAR</i> gene in dyschromatosis symmetrica hereditaria
Authors: Q. Liu, L. Jiang, W-L. Liu, X-J. Kang, Y. Ao, M. Sun, Y. Luo, Y. Song, W.H.Y. Lo, X. Zhang
Journal: British Journal of Dermatology (2006)

Background Dyschromatosis symmetrica hereditaria (DSH, MIM 127400) is a dominantly inherited skin disease associated with mutations in ADAR, the gene that encodes a double‐stranded RNA‐specific adenosine deaminase. We previously reported two novel ADAR mutations (p.Q513X and p.R916W) and confirmed the role of ADAR in Chinese patients with DSH. Both haploinsufficiency and a dominant‐negative effect have been suggested as the potential mechanism by which ADAR mutations cause DSH. Objectives To identify ADAR mutations in two additional Chinese DSH families and to obtain insight into the pathogenic mechanism of heterozygous ADAR mutations. Methods For mutation detection, all ADAR exons and their flanking intronic sequences were amplified and sequenced. Mutations were further confirmed by restriction analysis. Direct sequencing of cDNA fragments produced by reverse transcription–polymerase chain reaction (RT–PCR) and real‐time quantitative RT–PCR were used to examine the expression of ADAR in peripheral lymphocytes isolated from affected individuals. Results A small deletion, c.1555delT (p.C519fs), and a missense mutation, c.3116A>G (p.K1039R), were found in families A and B, respectively. In individuals carrying p.Q513X or p.C519fs, sequencing of cDNA fragments indicated almost total loss of mRNA expression from the mutant alleles, and real‐time quantitative RT–PCR showed an approximately 50% reduction of ADAR expression. However, equal abundance of the wild‐type and mutant cDNA sequences without reduction of ADAR expression was found in a patient with the missense p.R916W mutation. These results suggest that both the nonsense p.Q513X and frameshift p.C519fs mutations have generated null alleles probably by nonsense‐mediated mRNA decay. Conclusions Two novel ADAR mutations were found in Chinese patients with DSH. Evidence for ADAR haploinsufficiency as a mechanism underlying the molecular pathogenesis of DSH was obtained.
Self-reported dermatological problems and use of prescribed topical drugs correlate with decreased quality of life: an epidemiological survey
Authors: K. Bingefors, M. Lindberg, D. Isacson
Journal: British Journal of Dermatology (2002)

Skin problems are common in the population. Although a substantial fraction of the population suffers from skin conditions, we still have little information on how this affects the everyday life of the individuals concerned.To evaluate the impact of skin disease on health-related quality of life (HRQOL) measured with the Short Form-36 (SF-36), a multidimensional generic HRQOL instrument, from an epidemiological perspective. A further aim was to study differences in HRQOL by use of non-prescription and prescription dermatological drugs.The survey was carried out in the county of Uppland, Sweden in a random sample of 8000 individuals aged 20-84 years, of whom 5404 (68%) answered the questionnaire.A large part of the population (20.5%) reported dermatological problems and/or use of topical dermatological drugs, with a higher frequency among women (23.3%) than men (17.3%). Persons reporting dermatological problems scored lower on all eight dimensions of the SF-36. This pattern, although weaker, persisted after adjusting for comorbid somatic as well as psychiatric diseases and complaints. Those using topical dermatological drugs on prescription generally scored lower than the other groups with skin problems: in particular, they evaluated personal health as poorer (general health perceptions), perceived more limitations in daily activities (role limitation because of emotional health problems) and felt more tired and worn out (vitality).The study shows that skin disorders constitute a substantial problem in the population and cause a significant decrease in HRQOL. Furthermore, the results of this population survey point out the need for further population-based studies more specifically aimed at dermatological problems and HRQOL.
Questions regarding the optimal use of bevacizumab in glioblastoma: a moving target
Authors: R. Stupp, M. Weller
Journal: Neuro-Oncology (2014)

The saga of bevacizumab in brain tumors has been ongoing for many years. Despite encouraging initial reports targeting the vascular endothelial growth factor (VEGF) pathway by a neutralizing monoclonal antibody (bevacizumab) or a receptor tyrosine kinase inhibitor (cediranib), the few subsequent controlled studies were largely disappointing. Opportunities for adequate clinical investigation with bevacizumab were missed or delayed for many years. Nevertheless, these agents undoubtedly have a clinically meaningful benefit in selected patients. However, we lackclinical or biomarkers allowing identification of specific patients that benefit from these therapies. The highly variable clinical practice reflects the contradictory reports and the paucity of prospective and controlled trials. The absence of adequate data also prevented regulatory approval in many countries, especially in the European Union, thus preventing access to bevacizumab for patients. Numerous basic questions remain unresolved years after the drug has entered routine clinical use. 1 Two reports analyzing retrospectively large institutional databases on management of recurrent glioblastoma appear in this issue of Neuro-Oncology, 2,3 and two pivotal prospective randomized trials on the use of bevacizumab in newly diagnosed patients were recently reported. 4,5 Thus, it is timely to briefly review some of the available data and discuss their limitations.