tbuckley/cabot-search huggingface dataset:
Recombinant interleukin 2 or 5, but not 3 or 4, induces maturation of resting mouse B lymphocytes and propagates proliferation of activated B cell blasts.
Authors: H Karasuyama, A Rolink, F Melchers
Journal: The Journal of Experimental Medicine (1988)

Plasmacytoma transformants of the X63-Ag8-653 cell line carrying an expression vector with either IL-2, -3, -4, or -5 cDNA were established that secrete the corresponding ILs at high rates. The four mouse ILs (mILs) were then tested as single ILs and in combinations for their effects on the maturation of resting and proliferation of activated normal mouse splenic B cells. mIL-3 and mIL-4 were inactive in all assays. mIL-2, as well as mIL-5, synergized with Ig-specific antibodies and B cell growth factor alpha (BCGF-alpha) to stimulate successive rounds of B cell division with LPS-activated B cells. This activity as BCGF-beta was effective at concentrations similar to those at which mIL-2 induced proliferation of the CTL-L T cell line, indicating a high-affinity interaction of both mIL-2 and mIL-5 with their corresponding receptors on activated B cells. mIL-5 and maybe IL-2 also induced maturation of resting B cells to Ig-secreting cells without proliferation. This B cell maturation factor (BMF) activity of mIL-5 was as effective as its BCGF-beta activity, while the BMF activity of mIL-2 was at least 10(2)-fold less effective. BMF activity of mIL-2, but not mIL-5, was blocked by anti-Il-2-R antibodies, indicating that mIL-2 and mIL-5 use separate receptors for B cell signaling. mIL-2, as well as mIL-5, furthermore, acted as filler activities when proliferation in the presence of Ig-specific antibodies and BCGF-alpha was measured with as little as 500 B cells. In the case of mIL-5, this was also true for maturation of that few cells. Limiting dilution analyses showed that approximately 1-2% of the resting B cells matured without division, while 30-100-fold fewer cells (0.03-0.06%) proliferated and matured in response to IL-5. A single IL, therefore, is capable of inducing maturation and of stimulating mitotic cell cycle progression of normal B cells.
Clonal identity between skin and synovial tissue in a case of mycosis fungoides with polyarthritis
Authors: Yorick Sandberg, M'hamed El Abdouni, King H Lam, Anton W Langerak, Pieternella J Lugtenburg, Radboud J.E.M Dolhain, Freerk Heule
Journal: Journal of the American Academy of Dermatology (2004)
Catechol-O-methyltransferase (COMT): Biochemistry, Molecular Biology, Pharmacology, and Clinical Efficacy of the New Selective COMT Inhibitors
Authors: Pekka T. Männistö, Seppo Kaakkola
Journal: Pharmacological Reviews (1999)

[Axelrod et al. (1958)][1] first described the enzyme-catalyzed O- methylation of catecholamines and other catechols in the late 1950s. The enzyme responsible for the O- methylation, catechol- O -methyltransferase (COMT; EC[2.1.1.6][2]),2 was partly purified and characterized by the same group ([
CXCR4 and SDF1 expression in human meningiomas: A proliferative role in tumoral meningothelial cells in vitro1
Authors: Adriana Bajetto, Federica Barbieri, Alessandra Pattarozzi, Alessandra Dorcaratto, Carola Porcile, Jean Louis Ravetti, Gianluigi Zona, Renato Spaziante, Gennaro Schettini, Tullio Florio
Journal: Neuro-Oncology (2006)

Chemokines participate in cellular processes associated with tumor proliferation, migration, and angiogenesis. We previously demonstrated that stromal cell-derived factor 1 (SDF1) exerts a mitogenic activity in glioblastomas through the activation of its receptor CXCR4. Here we studied the expression of this chemokine in human meningiomas and its possible role in cell proliferation. Reverse transcriptase-PCR analysis for CXCR4 and SDF1 was performed on 55 human meningiomas (47 WHO grade I, 5 WHO II, and 3 WHO III). Immunolabeling for CXCR4 and SDF1 was performed on paraffin-embedded sections of these tumors. [3H]Thymidine uptake and Western blot analyses were performed on primary meningeal cell cultures of tumors to evaluate the proliferative activity of human SDF1α (hSDF1α) in vitro and the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) activation in this process. CXCR4 mRNA was expressed by 78% of the tumor specimens and SDF1 mRNA by 53%. CXCR4 and SDF1 were often detected in the same tumor tissues and colocalized with epithelial membrane antigen immunostaining. In 9 of 12 primary cultures from meningiomas, hSDF1α induced significant cell proliferation that was strongly reduced by the mitogen-activated protein kinase kinase inhibitor PD98059, involving ERK1/2 activation in the proliferative signal of hSDF1α. In fact, CXCR4 stimulation led to ERK1/2 phosphorylation/activation. In addition, the hSDF1α-induced cell proliferation was significantly correlated with the MIB1 staining index in the corresponding surgical specimen. In conclusion, we found that human meningiomas express CXCR4 and SDF1 and that hSDF1α induces proliferation in primary meningioma cell cultures through the activation of ERK1/2.
Overexpression of the MicroRNA <i>hsa-miR-200c</i> Leads to Reduced Expression of Transcription Factor 8 and Increased Expression of E-Cadherin
Authors: Gregory J. Hurteau, J. Andrew Carlson, Simon D. Spivack, Graham J. Brock
Journal: Cancer Research (2007)

Abstract MicroRNAs are ∼22-nucleotide sequences thought to interact with multiple mRNAs resulting in either translational repression or degradation. We previously reported that several microRNAs had variable expression in mammalian cell lines, and we examined one, miR-200c, in more detail. A combination of bioinformatics and quantitative reverse transcription-PCR was used to identify potential targets and revealed that the zinc finger transcription factor transcription factor 8 (TCF8; also termed ZEB1, δEF1, Nil-2-α) had inversely proportional expression levels to miR-200c. Knockout experiments using anti-microRNA oligonucleotides increased TCF8 levels but with nonspecific effects. Therefore, to investigate target predictions, we overexpressed miR-200c in select cells lines. Ordinarily, the expression level of miR-200c in non–small-cell lung cancer A549 cells is low in contrast to normal human bronchial epithelial cells. Stable overexpression of miR-200c in A549 cells results in a loss of TCF8, an increase in expression of its regulatory target, E-cadherin, and altered cell morphology. In MCF7 (estrogen receptor–positive breast cancer) cells, there is endogenous expression of miR-200c and E-cadherin but TCF8 is absent. Conversely, MDA-MB-231 (estrogen receptor–negative) cells lack detectable miR-200c and E-cadherin (the latter reportedly due to promoter region methylation) but express TCF8. The ectopic expression of miR-200c in this cell line also reduced levels of TCF8, restored E-cadherin expression, and altered cell morphology. Because the down-regulation of E-cadherin is a crucial event in epithelial-to-mesenchymal transition, loss of miR-200c expression could play a significant role in the initiation of an invasive phenotype, and, equally, miR-200c overexpression holds potential for its reversal. [Cancer Res 2007;67(17):7972–6]
Estrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease
Authors: Ruth A. Mulnard, Carl W. Cotman, Claudia Kawas, Christopher H. van Dyck, Mary Sano, Rachelle Doody, Elizabeth Koss, Eric Pfeiffer, Shelia Jin, Anthony Gamst, Michael Grundman, Ronald Thomas, Leon J. Thal, None for the Alzheimer's Disease Cooperative Study
Journal: JAMA (2000)

ContextSeveral reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women.ObjectiveTo determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD.DesignThe Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999.SettingThirty-two study sites in the United States.ParticipantsA total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy.InterventionsParticipants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial.Main Outcome MeasuresThe primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up.ResultsThe CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01).ConclusionsEstrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.
Exercise training and inspiratory muscle training in patients with bronchiectasis
Authors: C Newall
Journal: Thorax (2005)

<b>Background:</b> Bronchiectasis is a chronic suppurative lung disease often characterised by airflow obstruction and hyperinflation, and leading to decreased exercise tolerance and reduced health status. The role of pulmonary rehabilitation (PR) and inspiratory muscle training (IMT) has not been investigated in this group of patients. <b>Methods:</b> Thirty two patients with idiopathic bronchiectasis were randomly allocated to one of three groups: PR plus sham IMT (PR-SHAM), PR plus targeted IMT (PR-IMT), or control. All patients (except the control group) underwent an 8 week training programme of either PR or PR plus targeted IMT. Exercise training during PR was performed three times weekly at 80% of the peak heart rate. IMT was performed at home for 15 minutes twice daily over the 8 week period. <b>Results:</b> PR-SHAM and PR-IMT resulted in significant increases in the incremental shuttle walking test of 96.7 metres (95% confidence interval (CI) 59.6 to 133.7) and 124.5 metres (95% CI 63.2 to 185.9), respectively, and in endurance exercise capacity of 174.9% (95% CI 34.7 to 426.1) and 205.7% (95% CI 31.6 to 310.6). There were no statistically significant differences in the improvements in exercise between the two groups. Significant improvements in inspiratory muscle strength were also observed both in the PR-IMT group (21.4 cm H<sub>2</sub>O increase, 95% CI 9.3 to 33.4; p = 0.008) and the PR-SHAM group (12.0 cm H<sub>2</sub>O increase, 95% CI 1.1 to 22.9; p = 0.04), the magnitude of which were also similar (p = 0.220). Improvements in exercise capacity were maintained in the PR-IMT group 3 months after training, but not in the PR-SHAM group. <b>Conclusion:</b> PR is effective in improving exercise tolerance in bronchiectasis but there is no additional advantage of simultaneous IMT. IMT may, however, be important in the longevity of the training effects.
Evaluating Organizational Design To Assure Technology Transfer: The Case of the Community Clinical Oncology Program
Authors: A. D. Kaluzny, T. Ricketts, R. Warnecke, L. Ford, J. Morrissey, D. Gillings, E. J. Sondik, H. Ozer, J. Goldman
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Evaluating Organizational Design To Assure Technology Transfer: The Case of the Community Clinical Oncology Program Get access Arnold D. Kaluzny, Arnold D. Kaluzny * Health Services Research CenterChapel Hill, NC.School of Public Health and Lineberger Cancer Research CenterChapel Hill, NC. *Arnold D. Kaluzny, Ph.D., Health Services Research Center, University of North Carolina at Chapel Hill, Chase Hall, CB # 7490, Chapel Hill, NC 27599–7490. Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas Ricketts, III, Thomas Ricketts, III Health Services Research CenterChapel Hill, NC. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Warnecke, Richard Warnecke Survey Research LaboratoryChicago, IL. Search for other works by this author on: Oxford Academic PubMed Google Scholar Leslie Ford, Leslie Ford Community Oncology and Rehabilitation BranchBethesda, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph Morrissey, Joseph Morrissey Health Services Research CenterChapel Hill, NC. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dennis Gillings, Dennis Gillings Quintiles, Inc.Chapel Hill, NC. Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward J. Sondik, Edward J. Sondik Cancer Control Science Program, Division of Cancer Prevention and Control, National Cancer InstituteBethesda, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard Ozer, Howard Ozer School of Public Health and Lineberger Cancer Research CenterSchool of Medicine and Lineberger Cancer Research Center, University of North Carolina at Chapel HillChapel Hill, NC. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jay Goldman Jay Goldman School of Engineering, University of Alabama-BirminghamBirmingham, AL. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 22, 15 November 1989, Pages 1717–1725, https://doi.org/10.1093/jnci/81.22.1717 Published: 15 November 1989 Article history Received: 22 May 1989 Revision received: 09 August 1989 Accepted: 17 August 1989 Published: 15 November 1989
Polymerase Chain Reaction Based Method for the Detection of BCG Retention after Intravesical Instillation in Guinea Pig Bladders
Authors: Elizabeth C. de Boer, Alex C.C. Westerhof, Arend H.J. Kolk, Sjoukje Kuijper, Karl-Heinz Kurth, Denis H.J. Schamhart
Journal: European Urology (2000)
Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Fabrizio Luppi, Bianca Beghé, Luca Richeldi
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Comment on Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. [American Journal of Respiratory and Critical Care Medicine, 2010]
Recent Trends in U.S. Breast Cancer Incidence, Survival, and Mortality Rates
Authors: K. C. Chu, R. E. Tarone, L. G. Kessler, L. A. G. Ries, B. F. Hankey, B. A. Miller, B. K. Edwards
Journal: JNCI Journal of the National Cancer Institute (1996)

Background : Clinical trials have demonstrated that use of mammographic screening and advances in therapy can improve prognosis for women with breast cancer. Purpose : We determined the trends in breast cancer mortality rates, as well as incidence and survival rates by extent of disease at diagnosis, for white women in the United States and considered whether these trends are consistent with widespread use of such beneficial medical interventions. Methods : We examined mortality data from the National Center for Health Statistics and incidence and survival data by extent of disease from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, all stratified by patient age, using statistical-regression techniques to determine changes in the slope of trends over time. Results : The age-adjusted breast cancer mortality rate for U.S. white females dropped 6.8% from 1989 through 1993. A significant decrease in the slope of the mortality trend of approximately 2% per year was observed in every decade of age from 40 to 79 years of age. Trends in incidence rates were also similar among these age groups: localized disease rates increased rapidly from 1982 through 1987 and stabilized or increased more slowly thereafter; regional disease rates decreased after 1987; and distant disease rates have remained level over the past 20 years. Three-year relative survival rates increased steadily and significantly for both localized and regional disease from 1980 through 1989 in all ages, with no evidence of an increase in slope in the late 1980s. Implications : The decrease in the diagnosis of regional disease in the late 1980s in women over the age of 40 years likely reflects the increased use of mammography earlier in the 1980s. The increase in survival rates, particularly for regional disease, likely reflects improvements in systemic adjuvant therapy. Statistical modeling indicates that the recent drop in breast cancer mortality is too rapid to be explained only by the increased use of mammography; likewise, there has been no equivalent dramatic increase in survival rates that would implicate therapy alone. Thus, indications are that both are involved in the recent rapid decline in breast cancer mortality rates in the United States. [J Natl Cancer Inst 1996;88:1571–9]
A clinical sign of adenocystic tumour of the trachea
Authors: H. M. Singh, D. M. E. Thomas
Journal: Thorax (1973)

<b>Singh, H. M., and Thomas, D. M. E. (1973)</b>. <i>Thorax</i>, <b>28</b>, 442-443. <b>A clinical sign of adenocystic tumour of the trachea</b>. Three patients with intrathoracic adenocystic tumour of the trachea presented as difficult diagnostic problems. All three patients had been labelled as psychiatric problems. Present in two of the cases, the sniff sign proved diagnostic and occurred at a stage when occlusion of the trachea during expiration was almost total. In order to breathe, the patients drew in small sharp, sniffing breaths. The sign owes its name to this pattern of breathing.
Comparison of the clinical prediction model PREMM<sub>1,2,6</sub>and molecular testing for the systematic identification of Lynch syndrome in colorectal cancer
Authors: Fay Kastrinos, Ewout W Steyerberg, Judith Balmaña, Rowena Mercado, Steven Gallinger, Robert Haile, Graham Casey, John L Hopper, Loic LeMarchand, Noralane M Lindor, Polly A Newcomb, Stephen N Thibodeau, Sapna Syngal
Journal: Gut (2012)

<h3>Background</h3> Lynch syndrome is caused by germline mismatch repair (MMR) gene mutations. The PREMM<sub>1,2,6</sub> model predicts the likelihood of a MMR gene mutation based on personal and family cancer history. <h3>Objective</h3> To compare strategies using PREMM<sub>1,2,6</sub> and tumour testing (microsatellite instability (MSI) and/or immunohistochemistry (IHC) staining) to identify mutation carriers. <h3>Design</h3> Data from population-based or clinic-based patients with colorectal cancers enrolled through the Colon Cancer Family Registry were analysed. Evaluation included MSI, IHC and germline mutation analysis for <i>MLH1</i>, <i>MSH2</i>, <i>MSH6</i> and <i>PMS2</i>. Personal and family cancer histories were used to calculate PREMM<sub>1,2,6</sub> predictions. Discriminative ability to identify carriers from non-carriers using the area under the receiver operating characteristic curve (AUC) was assessed. Predictions were based on logistic regression models for (1) cancer assessment using PREMM<sub>1,2,6</sub>, (2) MSI, (3) IHC for loss of any MMR protein expression, (4) MSI+IHC, (5) PREMM<sub>1,2,6</sub>+MSI, (6) PREMM<sub>1,2,6</sub>+IHC, (7) PREMM<sub>1,2,6</sub>+IHC+MSI. <h3>Results</h3> Among 1651 subjects, 239 (14%) had mutations (90 <i>MLH1</i>, 125 <i>MSH2</i>, 24 <i>MSH6</i>). PREMM<sub>1,2,6</sub> discriminated well with AUC 0.90 (95% CI 0.88 to 0.92). MSI alone, IHC alone, or MSI+IHC each had lower AUCs: 0.77, 0.82 and 0.82, respectively. The added value of IHC+PREMM<sub>1,2,6</sub> was slightly greater than PREMM<sub>1,2,6</sub>+MSI (AUC 0.94 vs 0.93). Adding MSI to PREMM<sub>1,2,6</sub>+IHC did not improve discrimination. <h3>Conclusion</h3> PREMM<sub>1,2,6</sub> and IHC showed excellent performance in distinguishing mutation carriers from non-carriers and performed best when combined. MSI may have a greater role in distinguishing Lynch syndrome from other familial colorectal cancer subtypes among cases with high PREMM<sub>1,2,6</sub> scores where genetic evaluation does not disclose a MMR mutation.
Graft Loss and Acute Coronary Syndromes after Renal Transplantation in the United States
Authors: Kevin C. Abbott, Jay R. Bucci, David Cruess, Allen J. Taylor, Lawrence Y.C. Agodoa
Journal: Journal of the American Society of Nephrology (2002)

The impact of graft loss on acute coronary syndromes (ACS) after renal transplantation has not been studied in a national population. It was hypothesized that ACS might be more frequent after graft loss, as many of the benefits of a functioning allograft on metabolism and volume regulation would be lost. Data from the 2000 United States Renal Data System (USRDS) was used to conduct an historical cohort study of ACS in 14,237 patients who received renal transplants between April 1, 1995, and June 30, 1998, (followed until April 28, 2000) with valid information from CMS Form 2728, excluding patients with hospitalized ACS before renal transplant. Cox nonproportional regression models were used to calculate the time-dependent adjusted hazard ratio (AHR) of graft loss (censored for death) for time-to-first hospitalization for ACS (International Classification of Diseases 9th Modification Diagnosis Codes [ICD9] code 410.x or 411.x) occurring after transplant. The incidence of ACS was 12.1 per 1000 patient-years (PY) in patients after graft loss versus 6.5 per 1000 PY after transplantation (excluding patients with graft loss). As a time-dependent variable, graft loss had an AHR of 2.54 (95% confidence interval, 1.09 to 5.96; P = 0.031 by Cox regression). Other risk factors associated with ACS included diabetes, older recipient, and male recipient. Allograft rejection was NS. Renal transplant recipients share some of the risk factors for ACS with the general population. In addition, graft loss was identified as a unique risk factor for ACS in this population.
Cross-competition of CD8+ T cells shapes the immunodominance hierarchy during boost vaccination
Authors: Wolfgang Kastenmuller, Georg Gasteiger, Julian H. Gronau, Robert Baier, Ronny Ljapoci, Dirk H. Busch, Ingo Drexler
Journal: The Journal of Experimental Medicine (2007)

CD8+ T cell responses directed against multiple pathogen-derived epitopes are characterized by defined immunodominance hierarchy patterns. A possible explanation for this phenomenon is that CD8+ T cells of different specificities compete for access to epitopes on antigen-presenting cells, and that the outcome of this so-called cross-competition reflects the number of induced T cells. In our study using a vaccinia virus infection model, we found that T cell cross-competition is highly relevant during boost vaccination, thereby shaping the immunodominance hierarchy in the recall. We demonstrate that competition was of no importance during priming and was unaffected by the applied route of immunization. It strongly depended on the timing of viral antigen expression in infected APCs, and it was characterized by poor proliferation of T cells recognizing epitopes derived from late viral proteins. To our knowledge, this is the first demonstration of the functional importance of T cell cross-competition during a viral infection. Our findings provide a basis for novel strategies for how boost vaccination to defined antigens can be selectively improved. They give important new insights into the design of more efficient poxviral vectors for immunotherapy.