tbuckley/cabot-search huggingface dataset:
The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver.
Authors: Y S Li, K Hayakawa, R R Hardy
Journal: The Journal of Experimental Medicine (1993)

The expression of B lineage associated genes during early B cell differentiation stages is not firmly established. Using cell surface markers and multiparameter flow cytometry, bone marrow (BM) cells can be resolved into six fractions, representing sequential stages of development; i.e., pre-Pro-B, early Pro-B, late Pro-B/large Pre-B, small Pre-B, immature B, and mature B cells. Here we quantitate the levels of several B lineage associated genes in each of these fractions by RT-PCR, demonstrating different patterns of expression. We find that expression of terminal deoxynucleotidyl transferase (TdT), lambda 5, and VpreB is predominantly restricted to the Pro-B stages. Rag-1 and Rag-2 expression is also tightly regulated, and is found largely in the Pro-B through small Pre-B stages. Mb-1 is present from Pro-B throughout the pathway at high levels. Finally, Bcl-2 is expressed at high levels only at the pre-Pro-B and mature B stages, whereas it is low during all the intermediate stages. We also correlate this expression data with an analysis of the onset of Ig gene rearrangement as assessed by amplifying D-JH, VH-DJH, and VK-JK. Finally, we report differences in gene expression during B lymphopoiesis at two distinct ontogenic timings, in fetal liver and adult BM: both TdT and the precursor lymphocyte regulated myosin-like light chain are expressed at high levels in the Pro-B cell stage in bone marrow, but are absent from the corresponding fraction in fetal liver. In contrast, lambda 5, VpreB, Rag-1, and Rag-2 are expressed at comparable levels.
Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease
Authors: J J Soler-Cataluna
Journal: Thorax (2005)

Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality.Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%.Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41).This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital.
Antisense Inhibition of Methylenetetrahydrofolate Reductase Reduces Cancer Cell Survival <i>In vitro</i> and Tumor Growth <i>In vivo</i>
Authors: Jitka Stankova, Jijun Shang, Rima Rozen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Many cancer lines are methionine dependent and decrease proliferation when methionine supply is limited. Methylenetetrahydrofolate reductase (MTHFR) generates the folate derivative for homocysteine remethylation to methionine. We investigated the effect of antisense-mediated inhibition of MTHFR on survival of human cancer cells. Experimental Design: We examined the in vitro and in vivo anticancer effects of a combination of MTHFR antisense and standard cytotoxic drugs. Results: Specific antisense against MTHFR (EX5) showed significant inhibitory effects on growth of human colon, lung, breast, prostate, and neuroblastoma tumor cells in vitro compared with that of the control oligonucleotide. Cytotoxic drugs (5-fluorouracil, cisplatin, or paclitaxel) potentiated the effect of EX5. In vivo, antisense alone or in combination with cytotoxic drugs inhibited the growth of human colon and lung carcinoma xenografts. In comparison with control oligonucleotide, treatment with EX5 inhibited growth of colon tumors and lung tumors by 60% and 45%, respectively. EX5 with 5-fluorouracil decreased growth of colon tumors by an additional 30% compared with EX5 alone, and EX5 with cisplatin decreased growth of lung tumors by an additional 40% compared with cisplatin alone. Growth inhibition by EX5 was associated with decreased amounts of MTHFR protein and with increased amounts of an apoptosis marker. Conclusions: Our results confirm that MTHFR inhibition decreases tumor growth and suggest that inhibition of MTHFR by antisense or small molecules may be a novel anticancer approach.
Adaptive support ventilation for faster weaning in COPD: a randomised controlled trial
Authors: C. Kirakli, I. Ozdemir, Z.Z. Ucar, P. Cimen, S. Kepil, S.A. Ozkan
Journal: European Respiratory Journal (2011)

Adaptive support ventilation (ASV) is a closed-loop ventilation mode that can act both as pressure support ventilation (PSV) and pressure-controlled ventilation. Weaning with ASV shows promising results, mainly in post-cardiac surgery patients. The aim of the present randomised controlled study was to test the hypothesis that weaning with ASV could reduce the weaning duration in patients with chronic obstructive pulmonary disease (COPD) when compared with PSV. From among 435 COPD patients admitted to the intensive care unit (ICU) during a 20-month period, 97 were enrolled. Patients were assigned at random to either ASV or PSV as a weaning mode. Compared with PSV, ASV provided shorter weaning times (median 24 (interquartile range 20-62) h versus 72 (24-144) h, p=0.041) with similar weaning success rates (35 out of 49 for ASV and 33 out of 48 for PSV). Length of stay in the ICU was also shorter with ASV but the difference was not statistically significant. This study suggests that ASV may be used in the weaning of COPD patients with the advantage of shorter weaning times. Further studies are needed to investigate the role and potential advantages of ASV in the weaning period of different patient groups.
Role of Body Surface Area in Dosing of Investigational Anticancer Agents in Adults, 1991-2001
Authors: S. D. Baker, J. Verweij, E. K. Rowinsky, R. C. Donehower, J. H. M. Schellens, L. B. Grochow, A. Sparreboom
Journal: JNCI Journal of the National Cancer Institute (2002)

The prescribed dose of anticancer agents is most commonly calculated using body surface area as the only independent variable, and it has been shown that this approach still results in large interpatient variability in drug exposure. Here, we retrospectively assessed the pharmacokinetics of 33 investigational agents tested in phase I trials from 1991 through 2001, as a function of body surface area in 1650 adult cancer patients. Twelve of the drugs were administered orally, 19 were administered intravenously, and two were administered by both routes. Body surface area-based dosing was statistically significantly associated with a reduction in interpatient variability in drug clearance for only five of the 33 agents: docosahexaenoic acid (DHA)-paclitaxel, 5-fluorouracil/eniluracil, paclitaxel, temozolomide, and troxacitabine. These results do not support the use of body surface area in dose calculations and suggest that alternate dosing strategies should be evaluated. We conclude that body surface area should not be used to determine starting doses of investigational agents in future phase I studies.
Household Transmission of 2009 Pandemic Influenza A (H1N1) Virus in the United States
Authors: Simon Cauchemez, Christl A. Donnelly, Carrie Reed, Azra C. Ghani, Christophe Fraser, Charlotte K. Kent, Lyn Finelli, Neil M. Ferguson
Journal: New England Journal of Medicine (2009)

As of June 11, 2009, a total of 17,855 probable or confirmed cases of 2009 pandemic influenza A (H1N1) had been reported in the United States. Risk factors for transmission remain largely uncharacterized. We characterize the risk factors and describe the transmission of the virus within households.
Scientists Navigate Bermuda Triangle Of Technology Transfer
Authors: A. Jacobs-Perkins
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Scientists Navigate Bermuda Triangle Of Technology Transfer Get access Andree Jacobs-Perkins Andree Jacobs-Perkins Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 7, 4 April 1990, Pages 546–548, https://doi.org/10.1093/jnci/82.7.546 Published: 04 April 1990
Antivirals for Treatment of Influenza
Authors: Jonathan Hsu, Nancy Santesso, Reem Mustafa, Jan Brozek, Yao Long Chen, Jessica P. Hopkins, Adrienne Cheung, Gayane Hovhannisyan, Liudmila Ivanova, Signe A. Flottorp, Ingvil Sæterdal, Arthur D. Wong, Jinhui Tian, Timothy M. Uyeki, Elie A. Akl, Pablo Alonso-Coello, Fiona Smaill, Holger J. Schünemann
Journal: Annals of Internal Medicine (2012)

Background: Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza. Purpose: To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza. Data Sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists. Study Selection: Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness. Data Extraction: Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. Data Synthesis: 74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low–quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine. Limitations: Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias. Conclusion: Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. Primary Funding Sources: World Health Organization and McMaster University.
Therapeutic strategies for advanced neuroendocrine carcinomas of jejunum/ileum and pancreatic origin
Authors: C. J. Auernhammer, B. Goke
Journal: Gut (2011)

Multimodal treatment options for advanced gastroenteropancreatic neuroendocrine tumours (NET) of jejunum/ileum and of pancreatic origin are reviewed. Current topics being discussed are: European Neuroendocrine Tumour Society 2006/7, American Joint Cancer Committee/Union Internationale Contre le Cancer 2009 and WHO 2010 recommendations for grading and staging of NET; surgery of the primary tumour in distant metastasised disease; surgery of metastatic liver disease and impact on survival; somatostatin analogues for symptom control and for tumour control; selective internal radiation therapy with 90Y-microspheres as novel local ablative therapy in liver metastases; peptide receptor radionuclide therapy; novel chemotherapy regimens (eg, temozolomide) and novel targeted therapies (eg, sunitinib and everolimus).
Impact of Pretreatment With Clopidogrel on Initial Patency and Outcome in Patients Treated With Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction
Authors: Pieter J. Vlaar, Tone Svilaas, Kevin Damman, Bart J.G.L. de Smet, Jan G.P. Tijssen, Hans L. Hillege, Felix Zijlstra
Journal: Circulation (2008)

The main goal of the initial treatment of ST-segment elevation myocardial infarction is prompt reperfusion of the infarct-related artery. The value of pretreatment with clopidogrel before primary percutaneous coronary intervention is currently unclear.Studies were retrieved through MEDLINE and Cochrane Controlled Trials Register searches over the past 20 years. Two authors independently performed the study selection and data extraction. Randomized controlled studies were included when the research subjects were unselected patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Pilot trials, studies that enrolled patients undergoing rescue percutaneous coronary intervention, and studies with angiographic assessment not performed by a core laboratory or 2 blinded investigators were excluded. Thirty-eight treatment groups, including 8429 patients, were included. Initial patency was higher in treatment groups in which patients received pretreatment with clopidogrel (34.3%; 95% confidence interval, 32.9 to 35.8) compared with those in which patients did not receive clopidogrel before initial coronary angiography (25.8%; 95% confidence interval, 24.5 to 27.1). In multivariate-weighted logistic regression analysis, pretreatment with clopidogrel was an independent predictor of early reperfusion (odds ratio, 1.51; 95% confidence interval, 1.31 to 1.74; P<0.0001) and improved clinical outcome.Initial patency and clinical outcome were improved in treatment groups that received pretreatment with clopidogrel. These results in patients undergoing primary percutaneous coronary intervention are in line with the experience of pretreatment with clopidogrel in elective patients, non-ST-elevation coronary syndromes, and thrombolytic studies.
Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention
Authors: Eugenia Nikolsky, Eve D. Aymong, Amir Halkin, Cindy L. Grines, David A. Cox, Eulogio Garcia, Roxana Mehran, James E. Tcheng, John J. Griffin, Giulio Guagliumi, Thomas Stuckey, Mark Turco, David A. Cohen, Manuela Negoita, Alexandra J. Lansky, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2004)
Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009
Authors: Seema Jain, Laurie Kamimoto, Anna M. Bramley, Ann M. Schmitz, Stephen R. Benoit, Janice Louie, David E. Sugerman, Jean K. Druckenmiller, Kathleen A. Ritger, Rashmi Chugh, Supriya Jasuja, Meredith Deutscher, Sanny Chen, John D. Walker, Jeffrey S. Duchin, Susan Lett, Susan Soliva, Eden V. Wells, David Swerdlow, Timothy M. Uyeki, Anthony E. Fiore, Sonja J. Olsen, Alicia M. Fry, Carolyn B. Bridges, Lyn Finelli
Journal: New England Journal of Medicine (2009)

During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics of patients who were hospitalized with 2009 H1N1 influenza in the United States from April 2009 to mid-June 2009.
Lung emptying in patients with acute respiratory distress syndrome: effects of positive end-expiratory pressure
Authors: E. Kondili, G. Prinianakis, H. Athanasakis, D. Georgopoulos
Journal: European Respiratory Journal (2002)

The pattern of lung emptying was studied in 10 mechanically-ventilated patients with acute respiratory distress syndrome. At four levels of positive end-expiratory pressure (PEEP) (0, 5, 10 and 15 cmH2O) tracheal (Ptr) and airway pressures (Paw), flow (V') and volume (V) were continuously recorded. Tidal volume was set between 0.5-0.6 L and V'/V curves during passive expiration were obtained. Expired volume was divided into five equal volume slices and the time constant (taue) and effective deflation compliance (Crs(eff)) of each slice was calculated by regression analysis of V/V' and postocclusion V/Ptr relationships, respectively. In each slice, the presence or absence of flow limitation was examined by comparing V'/V curves with and without decreasing Paw. For a given slice, total expiratory resistance (Rtot) (consisting of the respiratory system (Rrs), endotracheal tube (Rtube) and ventilator circuit (Rvent)) was calculated as the taue/Crs(eff) ratio. In the absence of flow limitation Rrs was obtained by subtracting Rtube and Rvent from Rtot, while in the presence of flow limitation Rrs equaled Rtot. The taue of the pure respiratory system (taue(rs)) was calculated as the product of Rrs and Crs(eff). At zero PEEP, taue(rs) increased significantly towards the end of expiration (52+/-31%) due to a significant increase in Rrs (46+/-36%). Application of PEEP significantly decreased Rrs at the end of expiration and resulted in a faster and relatively constant rate of lung emptying. In conclusion, without positive end-expiratory pressure the respiratory system in patients with acute respiratory distress syndrome deflates with a rate that progressively decreases, due to a considerable increase in expiratory resistance at low lung volumes. Application of positive end-expiratory pressure decreases the expiratory resistance, probably by preventing airway closure, and as a result modifies the pattern of lung emptying.
Pathological observations of intrahepatic peribiliary glands in 1,000 consecutive autopsy livers. II. A possible source of cholangiocarcinoma
Authors: Tadashi Terada, Yasuni Nakanuma
Journal: Hepatology (1990)

It remains unclear whether atypical epithelial lesions, including carcinomas and precancerous lesions, develop in intraheptic peribiliary glands. This question was tested in this study. One thousand livers from consecutive autopsies were surveyed and 201 livers with bile duct carcinomas or metastatic malignant neoplasms were excluded because atypical epithelial lesions of the glands were difficult to distinguish from the primary or metastatic malignant cells. Consequently, 799 livers were examined for the atypical epithelial lesions by histological, mucin-histochemical and immunohistochemical methods. The atypical epithelial lesions were divisible into papillary hyperplasia, atypical hyperplasia and carcinomatous transformation. Of the 799 livers, papillary hyperplasia was only found in six livers (0.8%), papillary hyperplasia and atypical hyperplasia coexisted in four livers (0.5%) and carcinomatous transformation and atypical hyperplasia coexisted in one liver (0.1%). Mucin-histochemical study showed that the intracytoplasmic location of mucin was different between carcinomatous transformation and normal peribiliary glands. From an immunohistochemical standpoint, epithelial cells of the atypical epithelial lesions showed stronger immunoreactivities to carcinoembryonic antigen, carbohydrate antigen 19-9 and DU-PAN-2 than those of normal intrahepatic peribiliary glands. These findings suggest that intrahepatic cholangiocarcinomas arising from intrahepatic peribiliary glands actually exist, and that papillary and atypical hyperplasia of the peribiliary glands may precede this type of cholangiocarcinoma.
Improvement in Social Competence With Short-Term Atypical Antipsychotic Treatment: A Randomized, Double-Blind Comparison of Quetiapine Versus Risperidone for Social Competence, Social Cognition, and Neuropsychological Functioning
Authors: Philip D. Harvey, Thomas L. Patterson, Larry S. Potter, Kate Zhong, Martin Brecher
Journal: American Journal of Psychiatry (2006)

Objective: While neuropsychological test performance is correlated with social outcomes in patients with schizophrenia, there is little evidence to date that changes in neuropsychological performance are associated with changes in these outcomes. As part of an efficacy and tolerability study of atypical antipsychotics, the authors used a performance-based measure of social competence as a short-term outcome measure and examined the correlations between changes in social competence and improvements on neuropsychological tests. Method: Patients with schizophrenia were randomly assigned in a 1:1 ratio to receive treatment with either quetiapine (dose range: 200–800 mg/day) or risperidone (dose range: 2–8 mg/day) for an 8-week period. Results: Of 673 patients initially randomized, 289 had baseline and endpoint neuropsychological and functional competence data. Scores on the performance-based measure of social competence significantly improved with both treatments, as did a number of aspects of neuropsychological performance. Improvements in several aspects of neuropsychological performance were correlated with the extent of improvement in social competence. There were no overall differences between the treatments in their impact on social competence and neuropsychological performance. Conclusions: Short-term treatment with both quetiapine and risperidone resulted in improvements in social competence, with these improvements associated with improvements on some of the neuropsychological measures. In addition to their clinical importance, these results support the use of performance-based competence assessments as outcome measures in clinical trials.
Factor VIII Concentrates-Reply
Authors: G. Rock
Journal: JAMA (1986)

<h3>In Reply.—</h3> Our study was prompted in part by a sense of frustration at the apparent discrepancies between the stated drug content and the actual therapeutic effect of these preparations. Initially, our reports and those of others were greeted with a great degree of skepticism, both by the commercial providers of the concentrates and by other clinicians. We decided to report our results, even after apparent resolution of the difficulties, in order to ensure that there was a public record of these discrepancies. It is therefore with considerable consternation that I have read Dr Ratnoff's letter indicating that he continues to find discrepancies between the stated and actual contents of the vials of factor VIII concentrate. I do not doubt that this is the case, and I think that it points out, more than ever, the continued requirement for surveillance. Unless there is continuous monitoring and reporting of discrepancies, problems
Adjuvant high-dose intravenous gammaglobulin in the treatment of pemphigus and bullous pemphigoid: experience in six patients
Authors: R.C.Y. BECKERS, A. BRAND, B.J. VERMEER, B.W. BOOM
Journal: British Journal of Dermatology (1995)

At present, initial high‐dose prednisone is the treatment of choice for patients with pemphigus and bullous pemphigoid. To reduce the risks associated with long‐term corticosteroid treatment, other immunosuppressants are often given as steroid‐sparing agents. Occasionally, the dose of steroids cannot be reduced. In this study, we report six patients with pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid, in whom the daily corticosteroid dose could only be tapered to acceptable, effective, maintenance levels following treatment with high‐dose intravenous gammaglobulin.