tbuckley/cabot-search huggingface dataset:
Risk for Colon Adenomas in Patients with Rectosigmoid Hyperplastic Polyps
Authors: Dawn Provenzale
Journal: Annals of Internal Medicine (1990)

Objective: To determine whether hyperplastic polyps found in the rectosigmoid area of the colon are associated with proximal adenomas, and to judge whether patients with distal hyperplastic polyps found during sigmoidoscopy might benefit from full colonoscopy. Design: Data on patients having colonoscopy collected prospectively according to a set protocol. The size and location of all polyps were noted, and all polyps were biopsied. Setting: Two university hospitals. Patients: One thousand eight hundred and thirty-six consecutive patients referred for colonoscopy between 31 December 1987 and 31 August 1989. Results: Of the 970 patients who met eligibility requirements, 274 (28.3%) had adenomas and 108 (11.1%) had hyperplastic polyps. The proportion of patients with distal hyperplastic polyps and proximal adenomas (31.9%) was similar to the proportion of those without distal hyperplastic polyps (23.0%) (crude odds ratio, 1.57; 95% CI, 0.77 to 3.06). After adjusting for age and sex, the results were unchanged (adjusted odds ratio, 1.53; CI, 0.82 to 2.88). Patients with distal adenomas, on the other hand, were three times more likely to have proximal adenomas than those without distal adenomas (adjusted odds ratio, 3.42; CI, 1.99 to 5.88). Conclusions: Distal hyperplastic polyps are not strong predictors of risk for proximal adenomas. Based on the magnitude of the risk difference, we do not believe that finding a hyperplastic polyp during sigmoidoscopy justifies doing a full colonoscopy to search for proximal adenomas. Because rectosigmoid adenomas are associated with proximal adenomas, however, small polyps seen during sigmoidoscopy should be biopsied to determine their type. Colonoscopy should be reserved for patients who are proved to have adenomas.
The hepatitis C virus and immune evasion: non-structural 3/4A transgenic mice are resistant to lethal tumour necrosis factor mediated liver disease
Authors: L Frelin
Journal: Gut (2006)

The hepatitis C virus (HCV) establishes chronic infection by incompletely understood mechanisms. The non-structural (NS) 3/4A protease/helicase has been proposed as a key complex in modulating the infected hepatocyte, although nothing is known about the effects this complex exerts in vivo.To generate mice with stable and transient hepatocyte expression of the HCV NS3/4A proteins to study its effects in vivo.NS3/4A expression was determined by western blot and immunohistochemistry. Two independent pathologists determined the liver histology. Hepatic immunity was characterised by quantifying intrahepatic immune cell subsets. Liver damage was induced using carbon tetrachloride (CCl(4)), lipopolysaccaride (LPS), tumour necrosis factor alpha (TNFalpha), and anti-Fas antibody.Expression of NS3/4A was restricted to the cytoplasm of hepatocytes, and did not cause liver cancer or any spontaneous liver pathology. However, the presence of NS3/4A modulated the intrahepatic immunity, as follows: first, the CD4+ T cell and type I/II dendritic cell subsets were reduced in transgenic livers; second, NS3/4A protected hepatocytes from liver damage mediated in vivo by CCl(4), LPS, TNFalpha, but not FAS; and third, both stable and transiently NS3/4A transgenic mice were resistant to lethal doses of liver targeted TNFalpha, and the resistance could be reverted by treatment with a p38 mitogen activated protein kinase inhibitor (MAPK).Hepatic expression of NS3/4A does not induce spontaneous liver disease. NS3/4A does, however, alter the intrahepatic immune cell subsets and protects hepatocytes against TNFalpha induced liver damage in vivo. The TNFalpha resistance can be reverted by treatment with a p38 MAPK inhibitor. This represents a new immune evasion strategy conferred by NS3/4A.
Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production
Authors: Gregory C. Ippolito, Robert L. Schelonka, Michael Zemlin, Ivaylo I. Ivanov, Ryoki Kobayashi, Cosima Zemlin, G. Larry Gartland, Lars Nitschke, Jukka Pelkonen, Kohtaro Fujihashi, Klaus Rajewsky, Harry W. Schroeder
Journal: The Journal of Experimental Medicine (2006)

Tyrosine and glycine constitute 40% of complementarity determining region 3 of the immunoglobulin heavy chain (CDR-H3), the center of the classic antigen-binding site. To assess the role of DH RF1-encoded tyrosine and glycine in regulating CDR-H3 content and potentially influencing B cell function, we created mice limited to a single DH encoding asparagine, histidine, and arginines in RF1. Tyrosine and glycine content in CDR-H3 was halved. Bone marrow and spleen mature B cell and peritoneal cavity B-1 cell numbers were also halved, whereas marginal zone B cell numbers increased. Serum immunoglobulin G subclass levels and antibody titers to T-dependent and T-independent antigens all declined. Thus, violation of the conserved preference for tyrosine and glycine in DH RF1 alters CDR-H3 content and impairs B cell development and antibody production.
Molecular Characteristics of Bronchioloalveolar Carcinoma and Adenocarcinoma, Bronchioloalveolar Carcinoma Subtype, Predict Response to Erlotinib
Authors: Vincent A. Miller, Gregory J. Riely, Maureen F. Zakowski, Allan R. Li, Jyoti D. Patel, Robert T. Heelan, Mark G. Kris, Alan B. Sandler, David P. Carbone, Anne Tsao, Roy S. Herbst, Glenn Heller, Marc Ladanyi, William Pao, David H. Johnson
Journal: Journal of Clinical Oncology (2008)

Purpose We conducted this phase II trial to determine the efficacy of erlotinib in patients with bronchioloalveolar carcinoma (BAC) and adenocarcinoma, BAC subtype, and to determine molecular characteristics associated with response. Patients and Methods Patients (n = 101) with BAC (n = 12) or adenocarcinoma, BAC subtype (n = 89), were enrolled. All patients received erlotinib 150 mg daily. Epidermal growth factor receptor (EGFR) mutation, EGFR copy number, EGFR immunohistochemistry (IHC), and KRAS mutation status were analyzed in available tumors. The primary end point was response rate (RR). Results Overall RR was 22% (95% CI, 14% to 31%). In patients with pure BAC, the RR and median survival were 20% and 4 months, as compared with 23% and 19 months in those with adenocarcinoma, BAC subtype. No patient (zero of 18; 95% CI, 0% to 19%) whose tumor harbored a KRAS mutation responded to erlotinib. Patients with EGFR mutations had an 83% RR (15 of 18; 95% CI, 65% to 94%) and 23-month median OS. On univariate analysis, EGFR mutation and copy number were associated with RR and PFS. EGFR IHC was not associated with RR or progression-free survival (PFS). After multivariate analysis, only EGFR mutation was associated with RR and PFS. No molecular factors were associated with overall survival. Conclusion Erlotinib is active in BAC and adenocarcinoma, mixed subtype, BAC. Testing for EGFR and KRAS mutations can predict RR and PFS after treatment with erlotinib in this histologically enriched subset of patients with non–small-cell lung cancer (NSCLC). These data suggest that histologic subtype and molecular characteristics should be reported in clinical trials in NSCLC using EGFR-directed therapy.
Possible Detection of Pancreatic Cancer by Plasma Protein Profiling
Authors: Kazufumi Honda, Yasuharu Hayashida, Tomoko Umaki, Takuji Okusaka, Tomoo Kosuge, Satoru Kikuchi, Mitsufumi Endo, Akihiko Tsuchida, Tatsuya Aoki, Takao Itoi, Fuminori Moriyasu, Setsuo Hirohashi, Tesshi Yamada
Journal: Cancer Research (2005)

Abstract The survival rate of pancreatic cancer patients is the lowest among those with common solid tumors, and early detection is one of the most feasible means of improving outcomes. We compared plasma proteomes between pancreatic cancer patients and sex- and age-matched healthy controls using surface-enhanced laser desorption/ionization coupled with hybrid quadrupole time-of-flight mass spectrometry. Proteomic spectra were generated from a total of 245 plasma samples obtained from two institutes. A discriminating proteomic pattern was extracted from a training cohort (71 pancreatic cancer patients and 71 healthy controls) using a support vector machine learning algorithm and was applied to two validation cohorts. We recognized a set of four mass peaks at 8,766, 17,272, 28,080, and 14,779 m/z, whose mean intensities differed significantly (Mann-Whitney U test, P &amp;lt; 0.01), as most accurately discriminating cancer patients from healthy controls in the training cohort [sensitivity of 97.2% (69 of 71), specificity of 94.4% (67 of 71), and area under the curve value of 0.978]. This set discriminated cancer patients in the first validation cohort with a sensitivity of 90.9% (30 of 33) and a specificity of 91.1% (41 of 45), and its discriminating capacity was further validated in an independent cohort at a second institution. When combined with CA19-9, 100% (29 of 29 patients) of pancreatic cancers, including early-stage (stages I and II) tumors, were detected. Although a multi-institutional large-scale study will be necessary to confirm clinical significance, the biomarker set identified in this study may be applicable to using plasma samples to diagnose pancreatic cancer.
GM-CSF therapy in pulmonary alveolar proteinosis
Authors: M G de Vega
Journal: Thorax (2002)

GM-CSF therapy in pulmonary alveolar proteinosisTreatment with granulocyte-macrophage colony stimulating factor (GM-CSF) has been shown to benefit a subset of patients with adult pulmonary alveolar proteinosis (PAP).A 47 year old woman with PAP, confirmed by lung biopsy, and severe physiological and symptomatic disturbances was not improved by repeated unilateral whole lung lavages.Six months after the last lavage we started treatment with daily subcutaneous GM-CSF in increasing doses beginning at 3 µg/kg.When a daily dose of 6 µg/kg was reached a haematological response was detected and dose escalation ceased.After 4 weeks at this dose the patient began to improve.By week 11 at a dose of 6 µg/kg/day the treatment was stopped and after a further 3 weeks without treatment she attained maximal clinical, radiological, and physiological improvement (from arterial oxygen tension (PaO 2 ) 6.1 kPa, alveolar-arterial oxygen gradient ((A-a)O 2 ) 8.2 kPa, total lung capacity (TLC) 63.3%, and carbon monoxide transfer factor (TLCO) 58.7% at diagnosis to 10.9 kPa, 2.6 kPa, 99%, and 101.1%, respectively).At that point, as the haematological parameters were normal, we decided empirically to restart treatment at a maintenance dose of 3 µg/kg/day twice a week to avoid relapse.Five months later, with no evidence of clinical deterioration or haematological response, treatment was stopped and after a further 18 months the patient remains symptom free.The successful remission of our patient, the seven published cases of GM-CSF in the treatment of PAP, 1-3 and the low incidence of side effects compared with the whole lung lavage technique prompt us to recommend GM-CSF as a first line treatment option in these patients.
Characteristics of tracheostomy phonation valves
Authors: H. Prigent, D. Orlikowski, M. B. Blumen, K. Leroux, L. Legrand, M. Lejaille, L. Falaize, M. Ruquet, J-C. Raphael, F. Lofaso
Journal: European Respiratory Journal (2006)

Phonation valves are commonly used devices that allow the restoration of speech in tracheostomised patients. However, their use should not compromise the physiological benefit of tracheostomy. Six commercialised phonation valves were studied in a dynamic set-up simulating a respiratory frequency of 20 breaths·min −1 , a tidal volume of 0.5 L and a peak flow rate of 0.5 L·s −1 . Resistance and additional work of breathing (WOB) were calculated. In 10 tracheostomised patients, evaluations using no phonation valve (baseline), and the most and one of the least resistive valves were carried out. Respiratory patterns and gas exchanges were recorded. Inspiratory difficulty was evaluated using the modified Borg scale. Valves displayed a wide array of resistance ranging 1.3–5.9 cmH 2 O·L −1 ·s −1 . Additional WOB varied with a ratio of 4.4 between the best and the worst valve. While the different clinical conditions did not modify respiratory patterns and gas exchanges, a significant effect on the Borg scale rating was observed using ANOVA and post hoc analysis of baseline versus worst valve and one of the best valves versus worst valve. In conclusion, the variety of aerodynamic characteristics of phonation valves should be considered when choosing the device, according to the underlying condition of the patients benefiting from their use.
Randomised controlled trial of an interactive multimedia decision aid on benign prostatic hypertrophy in primary
Authors: E. Murray, H. Davis, S. S. Tai, A. Coulter, A. Gray, A. Haines
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To determine whether a decision aid on benign prostatic hypertrophy influences decision making, health outcomes, and resource use. <b>Design:</b> Randomised controlled trial. <b>Setting:</b> 33 general practices in the United Kingdom. <b>Participants:</b> 112 men with benign prostatic hypertrophy. <b>Intervention:</b> Patients9 decision aid consisting of an interactive multimedia programme with booklet and printed summary. <b>Outcome measures:</b> Patients9 and general practitioners9 perceptions of who made the decision, decisional conflict scores, treatment choice and prostatectomy rate, American Urological Association symptom scale, costs, anxiety, utility, and general health status. <b>Results:</b> Both patients and general practitioners found the decision aid acceptable. A higher proportion of patients (32% <i>v</i> 4%; mean difference 28%, 95% confidence interval 14% to 41%) and their general practitioners (46% <i>v</i> 25%; 21%, 3% to 40%) perceived that treatment decisions had been made mainly or only by patients in the intervention group compared with the control group. Patients in the intervention group had significantly lower decisional conflict scores than those in the control group at three months (2.3 <i>v</i> 2.6; −0.3, −0.5 to −0.1, P&lt;0.01) and this was maintained at nine months. No differences were found between the groups for anxiety, general health status, prostatic symptoms, utility, or costs (excluding costs associated with the video disc equipment). <b>Conclusions:</b> The decision aid reduced decisional conflict in men with benign prostatic hypertrophy, and the patients played a more active part in decision making. Such programmes could be delivered cheaply by the internet, and there are good arguments for coordinated investment in them, particularly for conditions in which patient utilities are important. <h3>What is already known on this topic</h3> Patients want more information about their condition and treatment options, and many want to play an active part in decision making Decision aids improve patients9 knowledge of their conditions and treatment options <h3>What this study adds</h3> The decision aid was highly acceptable to both the patients and their general practitioners Decisional conflict was reduced in the intervention group Patients who viewed the programme played a more active part in the decision making process and were less anxious than control patients Such aids could be introduced throughout the NHS at relatively low cost by using the internet
The Treatment of Acetaminophen Poisoning
Authors: L F Prescott, J A J H Critchley
Journal: The Annual Review of Pharmacology and Toxicology (1983)

Acetaminophen has become a very popular over-the-counter analgesic in some countries and as a result it is used increasingly as an agent for self-poisoning. Without treatment only a minority of patients develop severe liver damage and 1 to 2% die in hepatic failure. Until Mitchell and his colleagues discovered the biochemical mechanisms of toxicity in 1973 there was no effective treatment. They showed that the metabolic activation of acetaminophen resulted in the formation of a reactive arylating intermediate, and that hepatic reduced glutathione played an essential protective role by preferential conjugation and inactivation of the metabolite. Early treatment with sulphydryl compounds and glutathione precursors has been dramatically effective in preventing liver damage, renal failure, and death following acetaminophen overdosage. It seems likely that these agents act primarily by stimulating glutathione synthesis. Inhibition of the metabolic activation of acetaminophen is another potential therapeutic approach that has not yet been put to the test clinically. The clinical management of acetaminophen poisoning has been transformed and it is particularly gratifying to have effective treatment based on a well established biochemical mechanism of toxicity. It is likely that effective treatment will be developed for toxicity caused through similar mechanisms by other agents.
The Plastid Chromosome of Atropa belladonna and its Comparison with that of Nicotiana tabacum: The Role of RNA Editing in Generating Divergence in the Process of Plant Speciation
Authors: Christian Schmitz-Linneweber, Ralph Regel, Tung Gia Du, Holger Hupfer, Reinhold G. Herrmann, Rainer M. Maier
Journal: Molecular Biology and Evolution (2002)

The nuclear and plastid genomes of the plant cell form a coevolving unit which in interspecific combinations can lead to genetic incompatibility of compartments even between closely related taxa. This phenomenon has been observed for instance in Atropa-Nicotiana cybrids. We have sequenced the plastid chromosome of Atropa belladonna (deadly nightshade), a circular DNA molecule of 156,688 bp, and compared it with the corresponding published sequence of its relative Nicotiana tabacum (tobacco) to understand how divergence at the level of this genome can contribute to nuclear-plastid incompatibilities and to speciation. It appears that (1) regulatory elements, i.e., promoters as well as translational and replicational signal elements, are well conserved between the two species; (2) genes--including introns--are even more highly conserved, with differences residing predominantly in regions of low functional importance; and (3) RNA editotypes differ between the two species, which makes this process an intriguing candidate for causing rapid reproductive isolation of populations.
Effect of Protein Diet on Age-Dependent Methylation of Liver Nuclear Components of Mice Administered &lt;italic&gt;N&lt;/italic&gt;-Nitrosodimethylamine&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M Klaude, A von der Decken
Journal: JNCI Journal of the National Cancer Institute (1984)

Protein diets deficient or enriched in DL-methionine were studied for the effect of methylation of nuclear components in subadult and adult outbred albino male mice given N-nitrosodimethylamine. After the mice were fed diets for 6 days, they were given ip injections of [14C]N-nitrosodimethylamine (5 mg/kg body wt) and killed 45 minutes later. Liver nuclei were isolated; incorporation of 14C into nuclear proteins and methylation of DNA and RNA were determined. In the subadult and adult animals the nuclear protein content was diminished by shortage of a single essential amino acid. Incorporation of 14C into the total protein was reduced. The reduction amounted to 55% in the subadult and 23% in the adult animals. Neither an age-dependent nor a diet-dependent change in the specific methylation of DNA and RNA was observed. Analysis of methylation of DNA and RNA was observed. Analysis of methylated purine bases showed an age-related rise in O6-methylguanine in the adult as compared with the subadult mice.
Making Muscle
Authors: Michael D. Schneider
Journal: Circulation Research (2010)

T hose unnerved by the evolutionary relatedness between humans and chimpanzees might do well to consider the humble brewer's yeast, Saccharomyces cerevisiae, and fission yeast, S pombe. 1 At the biochemical level, we three are so similar that human orthologs can correct lethal defects of the corresponding yeast genes. 2,3Apart from merely single genes, this conservation extends to entire networks (eg, signal transduction by a web of protein kinases), modules (eg, cell cycle regulators), and multimolecular machines (eg, the telosome).For these reasons, although a stretch at first glance, yeast provide extraordinary insights into many underpinnings of cardiovascular medicine, shaping the course of research on cardiac muscle cell growth, proliferation, and aging. 4,5owever, for multicellular life, assembling the organism gives rise to a further job description: creating the right cell type, in precisely the right place, at the right time.Understanding this set of decisions and the responsible molecular circuits is a prerequisite if one is to appreciate the multiple ways in which developmental biology permeates cardiovascular medicine and to draw on this knowledge for translational benefits. 6The impact of cardiovascular development is most obvious with regard to congenital heart defects, often entailing mutations in heart-forming transcription factors and morphogens. 7Many of the same transcription factors are
Five cancer drugs back on NHS list after deals with drug companies
Authors: Nigel Hawkes
Journal: BMJ (2015)

Five cancer drugs have been reinstated on the list paid for by England’s Cancer Drugs Fund, after manufacturers provided discounts to make them more affordable.

The fund faces rising costs, and in September it announced the removal of 16 drugs used in 23 treatments, in an attempt to balance its books.1 Thanks to the new deal it has now been able to reinstate five, used in seven treatments, reducing the number of …
Immunophenotypic Analysis of AIDS-Related Diffuse Large B-Cell Lymphoma and Clinical Implications in Patients From AIDS Malignancies Consortium Clinical Trials 010 and 034
Authors: Amy Chadburn, April Chiu, Jeannette Y. Lee, Xia Chen, Elizabeth Hyjek, Alison H. Banham, Ariela Noy, Lawrence D. Kaplan, Joseph A. Sparano, Kishor Bhatia, Ethel Cesarman
Journal: Journal of Clinical Oncology (2009)

Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis.We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts.The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL.These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates.
Improved mucosal vaccines
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

![Graphic][1] 

Vaccine antigens coupled to an antibody (green) that binds to carbohydrates on M cells (right) induce a stronger immune response than when coupled to lectins (red). Pathogens that invade the mucosa are better repelled if the vaccines against them are delivered to the