tbuckley/cabot-search huggingface dataset:
Spontaneous exacerbation of disease activity in patients with chronic delta hepatitis infection: The role of hepatitis B, C or D?
Authors: Zvi Ackerman, Boontar Valinluck, John G. McHutchison, Allan G. Redeker, Sugantha Govindarajan
Journal: Hepatology (1992)

Forty-six patients with chronic hepatitis delta virus infection were followed between 6 and 116 mo (mean = 32.8 mo; median = 24 mo). Nineteen patients (41%) demonstrated clinical courses with episodes of biochemical reactivation (ALT levels greater than or equal to 10 times baseline values [group A]). Twenty-seven patients (59%) had stable clinical courses without biochemical reactivation (group B). Patients in group A were younger than those in group B (30.5 vs. 35.3 yr; p = 0.03), were less likely to be intravenous drug abusers (16% vs. 52%; p = 0.01) and were more likely to be homosexual (58% vs. 22%; p = 0.01). Serum hepatitis B virus DNA, hepatitis delta virus RNA, IgM antibody to HBc, HBeAg, antibody to HBe and IgG and IgM antibody to hepatitis delta virus were measured in all patients. In group A, these markers were studied before and during reactivation and during remission. In group B, these parameters were studied in a random fashion at 7- to 10-mo intervals. The presence of antibodies to human immunodeficiency virus and hepatitis C virus was assessed in all patients. A total of 38 biochemical reactivation episodes was noted among the 19 patients in group A. Eleven had sequential changes in hepatitis delta virus markers, suggesting that the exacerbations were due to hepatitis delta virus. In three, the sequential changes of viral markers were consistent with the exacerbations due to hepatitis B virus. In five other patients, no sequential changes in viral markers could be demonstrated to correlate with the biochemical exacerbations.(ABSTRACT TRUNCATED AT 250 WORDS)
Patient perceptions and recall of consent for regional anaesthesia compared with consent for surgery
Authors: Roxaneh Zarnegar, Matthew RD Brown, Matthew Henley, Victoria Tidman, Ahilan Pathmanathan
Journal: Journal of the Royal Society of Medicine (2015)

Objective In Britain, consent for surgery is documented using a Department of Health form signed by the surgeon and the patient. In contrast, anaesthetic procedures have no formalised consent process. Evidence on the process of consent for regional anaesthesia, and patient perceptions of this, is scarce outside obstetric practice. We aimed to determine patient recall and perceptions of consent for interscalene brachial plexus block and compared this to surgical consent for shoulder arthroplasty. Design Prospective observational survey. Setting A specialist musculoskeletal centre, UK. Participants Forty-six patients (female:male 30:16, mean age 61 years) undergoing shoulder arthroplasty with interscalene brachial plexus block. Main outcome measures Recall and understanding of consent for regional anaesthesia and surgery was examined using a semi-structured questionnaire 1–2 days after arthroplasty. Surgical consent forms and discussions recorded by the anaesthetist were examined in participants’ medical notes to compare against the level of recall. Analysis to determine statistical significance was conducted using McNemar’s test. Results Recall of surgical risks was overall significantly better than recall of brachial plexus block risks. Compared to their recollections of surgical risk, patients remembered fewer specific risks for brachial plexus block ( p &lt; 0.001). There were more patients unable to recall any risks when questioned about brachial plexus block than about their surgery ( p &lt; 0.05). One-third of patients did not regard the consent discussion about regional anaesthesia as important as consent for surgery and over one-quarter had not recognised the preoperative discussion about the brachial plexus block as a consent process similar to that conducted for surgery. Conclusions Fundamental misunderstandings about the consent process are prevalent. Future work in this area should seek to investigate how documentation of the consent process and patients’ understanding of consent for regional anaesthesia can be improved.
Multistate Analysis of Skeletal Events in Patients with Bone Metastases
Authors: Richard J. Cook, Pierre Major
Journal: Clinical Cancer Research (2006)

Abstract Cancer patients with bone metastases are at increased risk of experiencing skeletal events associated with severe morbidity. Clinical trials of palliative therapies must perform rigorous and robust evaluation of new treatments on the basis of meaningful summaries of the course of skeletal events over time, while dealing with potentially high mortality rates during observation. The purpose of this article is to present a multistate model that can be easily used to reflect possible courses of the disease process, indicate how simple methods of analysis can be used to estimate clinically relevant features of the process, and contrast this approach with some of the alternative methods. The relation between the multistate approach and previously used methods is highlighted.
Differentiation between two biologically distinct classes of group A streptococci by limited substitutions of amino acids within the shared region of M protein-like molecules.
Authors: D E Bessen, V A Fischetti
Journal: The Journal of Experimental Medicine (1990)

Group A streptococci can be categorized into two classes (I and II) based on immunodeterminants contained within a surface-exposed, conserved region (C repeat domain) of the major virulence factor, M protein. Previous studies have shown that several biological properties correlate strongly with streptococcal class, and thus, there is a strong impetus to precisely define the antigenic epitopes unique to class I and II M proteins. Using synthetic peptides, the binding sites of two class I-specific mAbs were mapped to distinct epitopes within the C repeat region of type 6 M protein (class I). A class II M protein-like gene (type 2) was cloned and sequenced, and the predicted amino acid sequence was compared for homology to class I and II molecules, whose sequences were previously reported. For a given C repeat block 35 amino acid residues in length, 20 residue positions were conserved among all sequences analyzed. Of the 15 variable amino acid positions, only four were class specific, and three of the four positions were localized in the area to which the class I-specific mAbs bound. The predicted secondary structures of class I and II C repeat blocks reveals that they are alpha-helical, except for a single area of disruption. In the class I molecules, the area of disruption corresponds to the class I-specific mAb binding sites. Importantly, the predicted conformational characteristics of this disruption differs for class I and II molecules. The data suggest that only limited changes in amino acid residues differentiate between class I and II molecules in the C repeat region. Therefore, selective (biological) pressures may have contributed to the evolution of these two classes of molecules.
[657] POTENTIAL RELEVANCE OF RAPID VIRAL RESPONSE FOR SVR AND OPTIMISATION OF THE TREATMENT OF HEPATITIS C (CHC) WITH PEGINTERFERON o-2a (PEG) AND RIBAVIRIN (RBV)
Authors: E. Zehnter, S. Mauss, K. Boeker, Th. Lutz, S. Racky, W. Schmidt, R. Ulrich, I. Sbrijer, R. Heyne, A. Schober, C. John, K.H. Hey, B. Bokemeyer, B. Kallinowski, B. Moeller, S. Pape, U. Alshuth, D. Hueppe
Journal: Journal of Hepatology (2007)
Some Thoughts on the Reporting of Adverse Events in Phase II Cancer Clinical Trials
Authors: Stewart J. Anderson
Journal: Journal of Clinical Oncology (2006)

In this issue, Scharf and Colevas 1 discuss discrepancies in adverse event (AE) reporting for phase II oncology trials in peerreviewed publications and the National Cancer Institute (NCI) Clinical Data Update System (CDUS). 2 Many published articles do not provide an appropriate lexicon for AE assessment, and published reports of AEs in phase II studies are problematic in the following three areas: underreporting of low-grade AEs, underreporting of recurrent AEs, and inconsistent and incomplete characterization and reporting of high-grade AEs. 1 The authors conclude that there is a lack of consistency between the definition of AEs in published trial results compared with the original study protocols, and published AE data markedly differ from the data available in CDUS.The authors suggest that journals set a standard of quality assurance for AE information.The authors based their conclusions on an analysis of 22 published reports of single-agent CDUS-monitored phase II clinical trials, culled from a potential pool of 355 single-and multipleagent CDUS-monitored phase II studies active between March 1998 and October 2003.In that time, the NCI Common Toxicity Criteria version 2.0 3 was the mandated lexicon for reporting and grading AEs in NCI-sponsored trials.Nevertheless, Scharf and Colevas 1 point out that only 16 (73%) of the 22 publications identified a specific AE criteria system, and only 13 publications (59%) cited the NCI Common Toxicity Criteria as the method of AE classification.
Longitudinal Bioluminescence Imaging of the Dynamics of Doxorubicin Induced Apoptosis
Authors: Gang Niu, Lei Zhu, Don N. Ho, Fan Zhang, Haokao Gao, Qimeng Quan, Naoki Hida, Takeaki Ozawa, Gang Liu, Xiaoyuan Chen
Journal: Theranostics (2013)

Objectives: Most chemotherapy agents cause tumor cell death primarily by the induction of apoptosis.The ability to noninvasively image apoptosis in vivo could dramatically benefit pre-clinical and clinical evaluation of chemotherapeutics targeting the apoptotic pathway.This study aims to visualize the dynamics of apoptotic process with temporal bioluminescence imaging (BLI) using an apoptosis specific bioluminescence reporter gene.Methods: Both UM-SCC-22B human head and neck squamous carcinoma cells and 4T1 murine breast cancer cells were genetically modified with a caspase-3 specific cyclic firefly luciferase reporter gene (pcFluc-DEVD).Apoptosis induced by different concentrations of doxorubicin in the transfected cells was evaluated by both annexin V staining and BLI.Longitudinal BLI was performed in xenografted tumor models at different time points after doxorubicin or Doxil treatment, to evaluate apoptosis.After imaging, DNA fragmentation in apoptotic cells was assessed in frozen tumor sections using TUNEL staining.Results: Dose-and time-dependent apoptosis induced by doxorubicin in pcFluc-DEVD transfected UM-SCC-22B and 4T1 cells was visualized and quantified by BLI.Caspase-3 activation was confirmed by both caspase activity assay and Glo TM luciferase assay.One dose of doxorubicin treatment induced a dramatic increase in BLI intensity as early as 24 h after treatment in 22B-pcFluc-DEVD xenografted tumors.Sustained signal increase was observed for the first 3 days and the fluorescent signal from ex vivo TUNEL staining was consistent with BLI imaging results.Long-term imaging revealed that BLI signal consistently increased and reached a maximum at around day 12 after the treatment with one dose of Doxil.Conclusions: BLI of apoptosis with pcFluc-DEVD as a reporter gene facilitates the determination of kinetics of the apoptotic process in a real-time manner, which provides a unique tool for drug development and therapy response monitoring.
Cisplatin and Radiotherapy With or Without Erlotinib in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Randomized Phase II Trial
Authors: Renato G. Martins, Upendra Parvathaneni, Julie E. Bauman, Anand K. Sharma, Luis E. Raez, Michael A. Papagikos, Furhan Yunus, Brenda F. Kurland, Keith D. Eaton, Jay J. Liao, Eduardo. Mendez, Neal Futran, David X. Wang, Xiaoyu Chai, Sarah G. Wallace, Melissa Austin, Rodney Schmidt, D. Neil Hayes
Journal: Journal of Clinical Oncology (2013)

The combination of cisplatin and radiotherapy is a standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Cetuximab-radiotherapy is superior to radiotherapy alone in this population, validating epidermal growth factor receptor (EGFR) as a target. Erlotinib is a small-molecule inhibitor of EGFR. Adding EGFR inhibition to standard cisplatin-radiotherapy may improve efficacy.Patients with locally advanced SCCHN were randomly assigned to receive cisplatin 100 mg/m(2) on days 1, 22, and 43 combined with 70 Gy of radiotherapy (arm A) or the same chemoradiotherapy with erlotinib 150 mg per day, starting 1 week before radiotherapy and continued to its completion (arm B). The primary end point was complete response rate (CRR), evaluated by central review. The secondary end point was progression-free survival (PFS). Available tumors were tested for p16 and EGFR by fluorescent in situ hybridization.Between December 2006 and October 2011, 204 patients were randomly assigned. Arms were well balanced for all patient characteristics including p16, with the exception of more women on arm A. Patients on arm B had more rash, but treatment arms did not differ regarding rates of other grade 3 or 4 toxicities. Arm A had a CRR of 40% and arm B had a CRR of 52% (P = .08) when evaluated by central review. With a median follow-up time of 26 months and 54 progression events, there was no difference in PFS (hazard ratio, 0.9; P = .71).Erlotinib did not increase the toxicity of cisplatin and radiotherapy in patients with locally advanced HNSCC but failed to significantly increase CRR or PFS.
ProSplicer: a database of putative alternative splicing information derived from protein, mRNA and expressed sequence tag sequence data
Authors: Hsien-Da Huang, Jorng-Tzong Horng, Chau-Chin Lee, Baw-Jhiune Liu
Journal: Genome biology (2003)

Abstract ProSplicer is a database of putative alternative splicing information derived from the alignment of proteins, mRNA sequences and expressed sequence tags (ESTs) against human genomic DNA sequences. Proteins, mRNA and ESTs provide valuable evidence that can reveal splice variants of genes. The alternative splicing information in the database can help users investigate the alternative splicing and tissue-specific expression of genes.
Risk Markers of Oral Cancer in Clinically Normal Mucosa As an Aid in Smoking Cessation Counseling
Authors: Jon Sudbø, Roy Samuelsson, Björn Risberg, Stig Heistein, Christian Nyhus, Margaretha Samuelsson, Ruth Puntervold, Eva Sigstad, Ben Davidson, Albrecht Reith, Åsmund Berner
Journal: Journal of Clinical Oncology (2005)

Quitting smoking may prevent oral cancer. Behavioral intervention to quit smoking may be more efficient if persons are assigned an individual risk of cancer.In this prospective study, we provided counseling and behavioral intervention toward smoking cessation, supplemented by genetic analyses in clinically normal oral mucosa of heavy smokers. Measurement of serum cotinine was used to assess changes in smoking habits.In cytologic scrapings from 275 heavy smokers with clinically normal mucosa, we found tetraploidy in four and aneuploidy in 19 persons (23 of 275; 8%). Twenty one (91%) of 23 persons with aneuploidy had quit or reduced their smoking habits at the 3-month follow-up, 20 (87%) of 23 persons had done so at 12 months, and 21 (91%) of 23 persons had done so at 24 months. Fifty-one (20%) of the 252 persons without genetic changes in their mucosa had quit or reduced their tobacco habits at the 3-month follow-up, 23 (9%) had done so at 12 months, and 17 (7%) had done so at 24 months (P < .001). After 24 months, normalization of DNA content to diploidy was observed in two of four persons with tetraploid (50%), and in 11 of 19 persons (58%) with aneuploid scrapings. One patient developed an oral carcinoma in the floor of the mouth: this patient had an aneuploid scraping obtained 43 months earlier and developed a leukoplakia 28 months before the carcinoma.Risk markers of oral cancer are present in clinically normal mucosa of heavy smokers, and such findings enhance the adherence to smoking cessation on counseling. Cytogenetic aberrations may normalize after quitting smoking.
Nerve-driven immunity: Neuropeptides regulate cytokine secretion of T cells and intestinal epithelial cells in a direct, powerful and contextual manner
Authors: M Levite, Y Chowers
Journal: Annals of Oncology (2001)

Throughout the body, immune cells of various types, both classical (such as T-cells) and less recognized (such as intestinal epithelial cells) are exposed to a variety of neurotransmitters secreted from local nerve fibers. Moreover, immune cells express specific neurotransmitter receptors. Based on the above we asked whether neurotransmitters. by direct interaction with their receptors, can either evoke or block immune functions in general, and cytokine secretion in particular. We found that several neuropeptides (SOM, Sub P, CGRP and NPY), in nM concentration and in the absence of any additional stimulatory molecules, induced a significant secretion of cytokines from Th0, Th1 and Th2 antigen specific T-cells. Moreover, some neuropeptides surprisingly drove committed Thl and Th2 populations to a 'forbidden' cytokine secretion: secretion of Th2 cytokines from Th1 cells, and vice versa. We further found that SOM by itself markedly affected the secretion of proinflammatory cytokines from intestinal epithelial cells, which play a major role in the gut immunity in the mucosal defense against invading microorganisms. Thus, somatostatin, through its specific receptor, inhibits (> 90%) of the spontaneous, TNF-alpha or bacteria (Salmonella)-induced secretion of IL-8 and IL-1beta from two intestinal epithelial cell lines. Taken together, these observations suggest that neuropeptides can by themselves induce both typical and atypical cytokine secretion from T-cells and intestinal epithelial cells. Since a myriad of immune reactivities are mediated by, and dependent on, specific cytokines secreted from immune cells, the neuropeptide-induced effects may have important implications for numerous physiological and pathological conditions, including autoimmune diseases, chronic inflammation and neoplasias.
A Likelihood-based Index of Protein Protein Binding Affinities with Application to Influenza HA Escape from Antibodies
Authors: T. Watabe, H. Kishino, L. de Oliveira Martins, Y. Kitazoe
Journal: Molecular Biology and Evolution (2007)

In many biological systems, proteins interact with other organic molecules to produce indispensable functions, in which molecular recognition phenomena are essential. Proteins have kept or gained their functions during molecular evolution. Their functions seem to be flexible, and a few amino acid substitutions sometimes cause drastic changes in function. In order to monitor and predict such drastic changes in the early stages in target populations, we need to identify patterns of structural changes during molecular evolution causing decreases or increases in the binding affinity of protein complexes. In previous work, we developed a likelihood-based index to quantify the degree to which a sequence fits a given structure. This index was named the sequence-structure fitness (SSF) and is calculated empirically based on amino acid preferences and pairwise interactions in the structural environment present in template structures. In the present work, we used the SSF to develop an index to measure the binding affinity of protein–protein complexes defined as the log likelihood ratio, contrasting the fitness of the sequences to the structure of the complex and that of the uncomplexed proteins. We applied the developed index to the complexes formed between influenza A hemagglutinin (HA) and four antibodies. The antibody–antigen binding region of HA is under strong selection pressure by the host immune system. Hence, examination of the long-term adaptation of HA to the four antibodies could reveal the strategy of the molecular evolution of HA. Two antibodies cover the HA receptor-binding region, while the other two bind away from the receptor-binding region. By focusing on branches with a significant decline in binding ability, we could detect key amino acid replacements and investigate the mechanism via conditional probabilities. The contrast between the adaptations to the two types of antibodies suggests that the virus adapts to the immune system at the cost of structural change.
Endosonography in diagnosing and staging duodenal villous adenoma.
Authors: T L Tio, L H Sie, P C Verbeek, L T De Wit, G N Tytgat
Journal: Gut (1992)

Endosonography was carried out in a patient with an extensive juxtapapillary tumour. Radiology and endoscopy were unable to distinguish a villous adenoma from an invasive carcinoma. Endosonography revealed a mucosal hypoechoic tumour without penetration into the submucosa and muscularis propria. The common bile duct, pancreatic duct, and pancreas were normal. Lymph node abnormalities were not found. Based on the endosonography findings, local surgical tumour resection was undertaken instead of a Whipple procedure. The histology of the resected specimen confirmed the endosonography diagnosis.
The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory.
Authors: A N Akbar, N Borthwick, M Salmon, W Gombert, M Bofill, N Shamsadeen, D Pilling, S Pett, J E Grundy, G Janossy
Journal: The Journal of Experimental Medicine (1993)

The bcl-2 gene product has been shown to prevent apoptotic cell death. We have now investigated the bcl-2 protein expression by resting and activated mature T cell populations. Freshly isolated CD45RO+ T cells within CD4+ and CD8+ subsets expressed significantly less bcl-2 than CD45RO- (CD45RA+) T cells (p &amp;lt; 0.001). When CD45RA+ T cells within both CD4+ and CD8+ subsets were activated in vitro, the transition to CD45RO phenotype was associated with a decrease in bcl-2 expression. Patients with acute viral infections such as infectious mononucleosis caused by Epstein-Barr virus infections or chickenpox, resulting from varicella zoster virus infection, had circulating populations of activated CD45RO+ T cells which also showed low bcl-2 expression. In these patients, a significant correlation was seen between low bcl-2 expression by activated T cells and their apoptosis in culture (r = 0.94, p &amp;lt; 0.001). These results suggest that the primary activation of T cells leads to the expansion of a population that is destined to perish unless rescued by some extrinsic event. Thus the suicide of CD45RO+ T cells could be prevented by the addition of interleukin 2 to the culture medium which resulted in a concomitant increase in the bcl-2 expression of these cells. Alternatively, apoptosis was also prevented by coculturing the activated T lymphocytes with fibroblasts, which maintained the viability of lymphoid cells in a restinglike state but with low bcl-2 expression. The paradox that the CD45RO+ population contains the primed/memory T cell pool yet expresses low bcl-2 and is susceptible to apoptosis can be reconciled by the observations that maintenance of T cell memory may be dependent on the continuous restimulation of T cells, which increases their bcl-2 expression. Furthermore, the propensity of CD45RO+ T cells to extravasate may facilitate encounter with fibroblast-like cells in tissue stroma and thus be an important additional factor which promotes the survival of selected primed/memory T cells in vivo.