tbuckley/cabot-search huggingface dataset:
Cyp1b1 Exerts Opposing Effects on Intestinal Tumorigenesis via Exogenous and Endogenous Substrates
Authors: Richard B. Halberg, Michele Campaigne Larsen, Tammy L. Elmergreen, Alex Y. Ko, Amy A. Irving, Linda Clipson, Colin R. Jefcoate
Journal: Cancer Research (2008)

Cytochrome P450 1B1 (Cyp1b1) metabolism contributes to physiologic functions during embryogenesis but also to carcinogenic activation of polycyclic aromatic hydrocarbons (PAH). We generated Cyp1b1-deficient mice carrying the Min allele of the adenomatous polyposis coli gene. These Cyp1b1-deficient Min mice developed twice as many tumors as Min controls, which, however, remained similar in size and histology. Tumors from older (130 days) Cyp1b1-deficient Min mice selectively exhibited focal areas of nuclear atypia associated with less organized epithelia. The metabolism of endogenous substrates by Cyp1b1, therefore, suppresses tumor initiation but also affects progression. Treatment of Min mice with 7,12-dimethylbenzanthracene (DMBA) doubled both tumor multiplicity and size within 20 days but not when mice lacked Cyp1b1. This was paralleled by an abnormal staining of crypts with beta-catenin, phospho-IkappaB kinase, and RelA, which may represent an early stage of tumorigenesis similar to aberrant crypt formation. Cyp1b1 deletion did not affect circulating DMBA and metabolites. Cyp1b1 expression was higher in the tumors compared with normal small intestines. Increased tumorigenesis may, therefore, arise from generation of DMBA metabolites by Cyp1b1 in the developing tumors. Benzo(a)pyrene (BP), which is similarly activated by Cyp1b1 in vitro, did not affect tumorigenesis in Min mice. By contrast, BP and DMBA each suppressed tumor multiplicity in the absence of Cyp1b1. Cyp1b1 metabolism of DMBA and endogenous oxygenation products may each affect a tumor-promoting nuclear factor-kappaB activation, whereas Ah receptor activation by PAH affects suppression. Tumorigenesis may, therefore, depend on activation of PAH by Cyp1b1 and on offsetting suppression by Cyp1b1 of endogenous tumor-enhancing substrates.
Correlates of Saphenous Vein Graft Hyperplasia and Occlusion 1 Year After Coronary Artery Bypass Grafting
Authors: Dai Une, Alexander Kulik, Pierre Voisine, Michel Le May, Marc Ruel
Journal: Circulation (2013)

Background— Intimal hyperplasia of saphenous vein grafts (SVGs) can lead to subsequent graft atherosclerosis and occlusion after coronary artery bypass grafting (CABG). This study examined whether patient characteristics, anatomic factors, and medications are associated with SVG intimal hyperplasia and occlusion after CABG. Methods and Results— We performed a post hoc analysis of the Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) trial, where 322 grafts were assessed by angiography and 90 grafts were examined by intravascular ultrasound at 1 year after CABG. We assessed the following correlates for intimal hyperplasia and occlusion: patient characteristics, discharge medications, target vessel characteristics, and SVG diameter. At 1 year, the SVG mean intimal area was 4.3±2.1 mm 2 , and the occlusion rate was 6.2% (13/209). Independent correlates of hyperplasia were larger SVG diameter (1.9±0.2 mm 2 /mm; P &lt;0.001), hypertension (0.7±0.3 mm 2 ; P =0.03), and grafting to the right coronary territory (0.6±0.3 mm 2 ; P =0.03), whereas statin (−0.8±0.3 mm 2 ; P =0.01) and β-blocker use (−1.0±0.4 mm 2 ; P =0.03) were associated with less hyperplasia. Low target vessel quality was an independent correlate of SVG occlusion (odds ratio, 5.2±3.1; P &lt;0.01). Conclusions— Hypertension, SVG diameter, grafting to the right coronary artery, and low quality of the target vessel correlate with the development of SVG hyperplasia or occlusion by 1 year after CABG, whereas β-blockers and statins are associated with less SVG disease. These new findings further our understanding of SVG remodeling after bypass surgery and may guide future research to help prevent post-CABG SVG disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00228423
Interstitial Doppler Optical Coherence Tomography as a Local Tumor Necrosis Predictor in Photodynamic Therapy of Prostatic Carcinoma: An <i>In vivo</i> Study
Authors: Beau A. Standish, Kenneth K.C. Lee, Xiao Jin, Adrian Mariampillai, Nigel R. Munce, Michael F.G. Wood, Brian C. Wilson, I. Alex Vitkin, Victor X.D. Yang
Journal: Cancer Research (2008)

Abstract We have tested the feasibility of real-time localized blood flow measurements, obtained with interstitial (IS) Doppler optical coherence tomography (DOCT), to predict photodynamic therapy (PDT)-induced tumor necrosis deep within solid Dunning rat prostate tumors. IS-DOCT was used to quantify the PDT-induced microvascular shutdown rate in s.c. Dunning prostate tumors (n = 28). Photofrin (12.5 mg/kg) was administered 20 to 24 hours before tumor irradiation, with 635 nm surface irradiance of 8 to 133 mWcm−2 for 25 minutes. High frequency ultrasound and calipers were used to measure the thickness of the skin covering the tumor and the location of the echogenic IS probe within it. A two-layer Monte Carlo model was used to calculate subsurface fluence rates within the IS-DOCT region of interest (ROI). Treatment efficacy was estimated by percent tumor necrosis within the ROI, as quantified by H&amp;E staining, and correlated to the measured microvascular shutdown rate during PDT treatment. IS-DOCT measured significant PDT-induced vascular shutdown within the ROI in all tumors. A strong relationship (R2 = 0.723) exists between the percent tumor necrosis at 24 hours posttreatment and the vascular shutdown rate: slower shutdown corresponded to higher treatment efficacy, i.e., more necrosis. Controls (needle + light, no drug, n = 3) showed minimal microvascular changes or necrosis (4% ± 1%). This study has correlated a biological end point with a direct and localized measurement of PDT-induced microvascular changes, suggesting a potential clinical role of on-line, real-time microvascular monitoring for optimizing treatment efficacy in individual patients. [Cancer Res 2008;68(23):9987–95]
Patients should have one point of contact for complaints, MPs are told
Authors: A. O'Dowd
Journal: BMJ (2014)

Patients and their families should have a single point of contact for any type of complaint about health services to simplify the NHS’s complaints system, MPs have been told.

Regulatory bodies appearing before the parliamentary health select committee said that the current system, though improved, was still confusing and overly complicated for the public. During an evidence session on 17 June for its inquiry into complaints and raising concerns, MPs asked about the scale of complaints being made.

David Behan, chief executive of the NHS regulator the Care Quality Commission, giving evidence, said, “We know that complaints generally in the NHS are increasing, and we know that referrals to ourselves about concerns in the NHS …
Silicone in the liver: possible late effects.
Authors: J Hunt, M J Farthing, L R Baker, P R Crocker, D A Levison
Journal: Gut (1989)

We describe two renal transplant recipients who presented with clinical and biochemical abnormalities of liver function in whom liver scarring and silicone particles were identified in the liver by light microscopy. The presence of silicon in the particles was confirmed by x-ray energy dispersive spectroscopy. In one patient liver abnormalities were first noted more than two years after haemodialysis was discontinued and in a second patient abnormalities were still present more than four years after successful kidney transplantation. No other specific cause for the chronic liver abnormalities was determined and we consider that these may be related to the presence of silicone degradation products in the liver. Other patients haemodialysed using a siliconised peristaltic blood pump insert system may also be a risk of developing similar late complications.
ESCAPE OF HUMAN IMMUNODEFICIENCY VIRUS FROM IMMUNE CONTROL
Authors: Andrew J. McMichael, Rodney E. Phillips
Journal: Annual Review of Immunology (1997)

▪ Abstract Cytotoxic T lymphocytes (CTL) play a crucial role in the attempt to control infection with human immunodeficiency virus (HIV). Variation in epitopes recognized by CTL is common and frequently offers potential escape routes for mutant virus. Proof of escape, however, requires demonstration of increased frequency of virus particles or provirus that carry the escape sequence. There are now several recorded examples of virus variants that escape from CTL and are then selected. Most dramatic are those in which the CTL response has been dominated by CTL recognizing a single epitope that has suddenly changed, resulting in escape to fixation. This has been seen both early and late in the infection, leaving no doubt that escape occurs. Such escape is likely to be favored when the antiviral CTL response is oligoclonal and focused on a small number of immunodominant epitopes. The heterogeneous CTL response seen in many HIV-infected patients may result from successive waves of virus escape followed by new CTL responses specific for subdominant epitopes. Mutant virus can escape by several different routes, including failure of the mutated peptide to bind to the presenting HLA molecule and altered interactions with T cell receptors (TCR), including antagonism.
P05.04 * A COMBINED STRATEGY FOR THE DETECTION OF BRAF FUSIONS IN PILOCYTIC ASTROCYTOMA USING RT-PCR AND FISH
Authors: H. R. Haynes
Journal: Neuro-Oncology (2014)

INTRODUCTION: Pilocytic astrocytomas (WHO grade I) are the most common paediatric gliomas. The FISH test for KIAA1549-BRAF fusions is most commonly used, but this is difficult to interpret. We aimed to develop a reverse-transcriptase and real-time PCR (RT-PCR) test as a first-line screen for the three most common KIAA1549-BRAF fusion variants. METHODS: A RT-PCR method for detecting KIAA1549-BRAF fusions from formalin-fixed paraffin-embedded (FFPE) brain tumour tissues (pilocytic astrocytoma) was developed based on Tian et al 2011. The three most common fusion variants are detected using this assay: exon 16 of KIAA1549 fused to exon 9 of BRAF, exon 15 of KIAA1549 fused to exon 9 of BRAF and exon 16 of KIAA1549 fused to exon 11 of BRAF fusion. GAPDH expression was used as a control. The three KIAA1549-BRAF fusion variants account for 96% of all the reported BRAF fusions in pilocytic astrocytomas; the 16-9 variant is the most common accounting for 63%, the 15-9 fusion accounts for 23% and the 16-11 fusion accounts for 10% (Jones et al 2008, Tian et al 2011, Lawson et al 2011, Cin et al 2011). RESULTS: The RT-PCR assay was initially validated on 12 samples previously tested by FISH or RT-PCR in a different laboratory. The RT-PCR assay had a sensitivity of 89% (8/9 - one sample tested positive by FISH but negative on RT-PCR) and a specificity of 100% (2/2). The failure rate was 8.3% (1/12). Sensitivity experiments showed that the fusion can be detected when present at a least 5% of the total cDNA content. 51 Neuropathology diagnostic FFPE samples from 42 pilocytic astrocytoma patients were then tested using the BRAF fusion RT-PCR assay. The overall pick-up rate was 54% (20/37 patients) Of the positive patients (20), 55% (11/20) had the 16-9 fusion and 45% (9/20) had the 15-9 fusion. Two patients had multiple fusions (2/20 positive patients, 10%) showing the 16-9 fusion and a low-level 16-11 fusion. No patients exclusively had the 16-11 fusion. Multiple biopsy samples were available for 8 patients. In 7/8 of the patients, the results from the multiple biopsies were identical. In one patient, both biopsies sampled had the 16-9 fusion but the 16-11 fusion was detected at a very low level in only one of the biopsies. This could be due to the very low expression of the 16-11 fusion in the tumour samples. The failure rate of the assay was 12% (5/42 patients). The failed samples were very small tumour samples and so RNA extraction from these biopsies was not successful. However the assay was successful on archived material, some of which were over 20 years old. CONCLUSIONS: We propose undertaking RT-PCR for BRAF fusion as a first-line test in all pilocytic astrocytoma referrals. If the result is negative or the RT-PCR fails, then FISH can be offered as a second-line test. This strategy would more than halve the number of FISH tests, reducing the burden of interpreting difficult and ambiguous cases.
Effect of intrajejunal elemental diet perfusion on jejunal secretion of immunoglobulins, albumin, and hyaluronan in man.
Authors: J F Colombel, J P Vaerman, R Hallgren, J P Dehennin, E Wain, R Modigliani, A Cortot
Journal: Gut (1992)

The aim of this work was to study the jejunal secretion of immunoglobulins (Ig), albumin, and hyaluronan in response to jejunal perfusion of an elemental diet. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with a control electrolyte solution for 80 minutes and with an elemental diet (containing 20.5 milligrams of free amino acids and 104.2 milligrams of oligosaccharides) for 100 minutes. The jejunal fluid concentrations of albumin, IgG, monomeric IgA (m-IgA), polymeric IgA (p-IgA), IgM, secretory component, and hyaluronan were measured and their jejunal outputs calculated. Within 20 minutes of starting perfusion with the elemental diet there was a significant increase in the secretion rates of albumin (x3.3), IgG (x5), M-IgA (x3.7), p-IgA (x2), IgM (x2), and secretory component (x1.6), but the hyaluronan secretion rate was not changed. The increase in m-IgA, p-IgA, IgM, and secretory component output suggests that intestinal perfusion of an elemental diet results in stimulation of secretory immunity. The increase in albumin and IgG output probably reflects a nutrient induced leakage from the plasma compartment.
Azurocidin and a homologous serine protease from neutrophils. Differential antimicrobial and proteolytic properties.
Authors: D Campanelli, P A Detmers, C F Nathan, J E Gabay
Journal: Journal of Clinical Investigation (1990)

Two 29-kD polypeptides, azurocidin and p29b, were purified to homogeneity from human neutrophils by acid extraction of azurophil granule membrane-associated material followed by gel filtration and reverse-phase chromatography. Azurocidin and p29b share NH2-terminal sequence homology with each other as well as with elastase, cathepsin G, and other serine proteases. p29b bound [3H]diisopropyl fluorophosphate and hydrolyzed elastin, casein, and hemoglobin. A peptide substrate for p29b could not be identified. Azurocidin neither bound [3H]diisopropyl fluorophosphate nor hydrolyzed any of the proteins, peptides, or esters tested. In microbicidal assays, purified azurocidin was comparable to p29b in activity against Escherichia coli, Streptococcus faecalis, and Candida albicans. The antimicrobial activity of azurocidin was enhanced under mildly acidic conditions, but was inhibited in a dose-dependent manner by NaCl, CaCl2, or serum. Immunoblot analysis with monospecific antibodies localized greater than 90% of the azurocidin and greater than 75% of the p29b to azurophil granule-rich fractions of PMN lysates. Immunoelectron microscopy confirmed the localization of azurocidin to the azurophil granules. Azurocidin associated with the azurophil granule membrane, but did not appear to be an integral membrane protein. Thus, azurocidin and p29b are members of a family of serine protease homologs stored in azurophil granules and may play a role in inflammatory and antimicrobial processes involving PMN.
Physical examination tests of the shoulder: a systematic review with meta-analysis of individual tests
Authors: E J Hegedus, A Goode, S Campbell, A Morin, M Tamaddoni, C T Moorman, C Cook
Journal: British Journal of Sports Medicine (2007)

Objective: To compile and critique research on the diagnostic accuracy of individual orthopaedic physical examination tests in a manner that would allow clinicians to judge whether these tests are valuable to their practice. Methods: A computer-assisted literature search of MEDLINE, CINAHL, and SPORTDiscus databases (1966 to October 2006) using keywords related to diagnostic accuracy of physical examination tests of the shoulder. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to critique the quality of each paper. Meta-analysis through meta-regression of the diagnostic odds ratio (DOR) was performed on the Neer test for impingement, the Hawkins−Kennedy test for impingement, and the Speed test for superior labral pathology. Results: Forty-five studies were critiqued with only half demonstrating acceptable high quality and only two having adequate sample size. For impingement, the meta-analysis revealed that the pooled sensitivity and specificity for the Neer test was 79% and 53%, respectively, and for the Hawkins−Kennedy test was 79% and 59%, respectively. For superior labral (SLAP) tears, the summary sensitivity and specificity of the Speed test was 32% and 61%, respectively. Regarding orthopaedic special tests (OSTs) where meta-analysis was not possible either due to lack of sufficient studies or heterogeneity between studies, the list that demonstrates both high sensitivity and high specificity is short: hornblowers’s sign and the external rotation lag sign for tears of the rotator cuff, biceps load II for superior labral anterior to posterior (SLAP) lesions, and apprehension, relocation and anterior release for anterior instability. Even these tests have been under-studied or are from lower quality studies or both. No tests for impingement or acromioclavicular (AC) joint pathology demonstrated significant diagnostic accuracy. Conclusion: Based on pooled data, the diagnostic accuracy of the Neer test for impingement, the Hawkins−Kennedy test for impingement and the Speed test for labral pathology is limited. There is a great need for large, prospective, well-designed studies that examine the diagnostic accuracy of the numerous physical examination tests of the shoulder. Currently, almost without exception, there is a lack of clarity with regard to whether common OSTs used in clinical examination are useful in differentially diagnosing pathologies of the shoulder.
Dietary Fatty Acids and Pancreatic Cancer in the NIH-AARP Diet and Health Study
Authors: Anne C. M. Thiébaut, Li Jiao, Debra T. Silverman, Amanda J. Cross, Frances E. Thompson, Amy F. Subar, Albert R. Hollenbeck, Arthur Schatzkin, Rachael Z. Stolzenberg-Solomon
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundPrevious research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive.
Registration of Left Ventricular Volume Curves in the Dog with the Systemic Circulation Intact
Authors: ARNOLD M. KATZ, LOUIS N. KATZ, FRANCIS L. WILLIAMS, Boyd Eugene
Journal: Circulation Research (1955)

A method is described whereby it is possible to obtain volume curves from the left ventricle of an open-chested dog with an essentially intact systemic circulation. Several applications of such univentricular records to the study of the heart's performance are suggested and examples of analyses from recorded curves are presented. Changes in the physicochemical properties of the myocardium are seen to accompany alterations in the chemical environment of the heart.
Radiotherapy for localized rectal cancer
Authors: E Deutsch, P Ezra, M Mangoni, M Ducreux
Journal: Annals of Oncology (2007)

Surgical resection alone was the standard treatment modality for localized rectal cancer until the early 1990s. Total mesorectal excision (TME) has become the actual standard of care for patients with rectal cancer which greatly reduces local recurrences. Despite the introduction of TME, radiotherapy and chemotherapy have prevailed as integral components of modern treatment concepts. The management of localized rectal cancer requires a multi-disciplinary approach with specialist surgeons, gastro-enterologists, and medical and radiation oncologists. The sequence of treatments is more important than ever. Recent studies have highlighted the central role of radiation therapy associated with surgery to optimize local control, especially in stages II and III rectal cancer, and neo-adjuvant radiochemotherapy (RCT) is now considered to be the standard. However, important questions about preoperative diagnosis, fractionation and dosing of shortand long-term radiation therapy, whether shortand long-term radiotherapy are comparable, and which chemotherapeutic drugs should be used in which combination and sequence remain to be answered. This article focuses on the indications of radiotherapy in the setting of rectal cancer, the benefits of concurrent chemoradiation and the integration of novel drugs into the strategy.
Rheumatoid Arthritis with Lung Lesions
Authors: T. M. L. Price, M. O. Skelton
Journal: Thorax (1956)

Eliman and Ball (1948) first adequately des- cribed lung lesions in rheumatoid arthritis, regarding them as part of the disease process and as affording further evidence of the tendency of this malady to produce lesions elsewhere than in the joints.Of their three cases, which clinically presented typical rheumatoid arthritis associated with signs of pulmonary disease, two came to post-mortem examination.Histologically the lungs showed patchy fibrosing pneumonitis and alveolar fibrosis which were believed by these authors to indicate rheumatoid damage to the lung parenchyma.Since then other cases have been described, most of them, however, without necropsy confirmation, although Christie (1954) described three cases with careful necropsy studies but without any full description of the radiological changes.More recently, Rubin (1955) described four similar cases, in three of which lung biopsy showed an appearance of fibrosing pneumonitis.We record here a further case of rheumatoid arthritis with severe lung disease and striking radiological changes in a patient in whom the diagnosis of "rheumatoid lung" was made during life and in whose case necropsy was performed.
Bacterial L-forms in the blood and joint fluids of arthritic subjects.
Authors: P Pease
Journal: Annals of the Rheumatic Diseases (1969)

The possibility that bacteria in a sub-cellular phase (including L-forms, mycoplasmata, and Bed- sonia) may be associated with arthritic disease has been much discussed, and it has been suggested (Pease, 1965, 1967a, 1968) that arthritis and other diseases with an autoimmune element could be initiated by a breakdown of immunological tolerance in respect of a widespread and normally tolerated parasite.The Gram-positive bacteria, often classi- fied as Listeria, that are frequent blood-parasites of man and other vertebrates, could fill this role, as they are found to occur in much greater numbers in arthritic subjects than in healthy persons (Alex- ander-Jackson, 1954; Fleisher, 1952; Pease, 1967a).Although the classification and identification of micro-organisms of this type are not easy, it is my opinion that the "diphtheroid" bacilli, isolated by Duthie, Stewart, Alexander, and Dayhoff (1967) from arthritic joints, are one of the phases of these bacteria, and that this is probably true of various other isolates.Bacterial L-forms and spheroplasts are not easy to detect by classical bacteriological methods, and may be missed completely (indeed it is apparent that they frequently have been missed by investi- gators who have found arthritic blood and joint fluids to be sterile).At the same time, since they may take a very long time to revert to the bacillary phase, on isolation, and may never do so, they are liable to be confused with mycoplasmata, which they closely resemble.Detection of Listeria L-forms, either directly in the blood and joint fluids, or in primary cultures, can best be achieved by electron or phase-contrast microscopy, and one of the objects of this paper is