tbuckley/cabot-search huggingface dataset:
Phenotype and proliferation of early B lymphocyte precursor cells in mouse bone marrow.
Authors: Y H Park, D G Osmond
Journal: The Journal of Experimental Medicine (1987)

Bone marrow cells were examined by double immunofluorescent labeling techniques to detect determinants for the B lineage monoclonal antibody, 14.8, the nuclear enzyme, terminal deoxynucleotidyl transferase (TdT), cytoplasmic mu chains (c mu), and surface mu (s mu). In 8-9-wk-old C3H/HeJ mice, 14.8+ cells totalled 22.2% of all marrow cells (35 X 10(5) cells/femur). While many 14.8+ cells were c mu+ s mu- pre-B cells and s mu+ B lymphocytes (17.0%), the remainder (5.2%) were large cells lacking mu chains. After injecting vincristine sulfate, these 14.8+ mu- cells accumulated in mitosis at a rate of 13.5%/h (turnover time, 7.4 h). Their calculated total production rate (41 X 10(6) cells/whole marrow/d) exceeded that previously determined for large pre-B cells, suggesting some cell loss from the B lineage. TdT+ cells made up 1.8% of marrow cells and were mainly medium-sized cells. They all lacked mu chains, but half (0.9%) bound 14.8 antibody at low to medium intensity. Three discrete cell populations were thus defined, differing in mean cell diameter TdT+ 14.8- mu-, 9.5 micron; TdT+ 14.8+ mu-, 10 microns; and TdT- 14.8+ mu-, 11.5 micron, presumptively representing a sequence of cell stages preceding the expression of mu chains in large pre-B cells (TdT- 14.8+ c mu+ s mu-, 11.5 microns). This work provides a tentative model of early progenitor cells and their proliferation in normal marrow as a basis for studies of perturbations and the control of B lymphocytopoiesis.
Loss of Nuclear p27 Expression and Its Prognostic Role in Relation to Cyclin E and p53 Mutation in Gastroenteropancreatic Neuroendocrine Tumors
Authors: Patricia Grabowski, Jörg Schrader, Julia Wagner, Dieter Hörsch, Rudolf Arnold, Christian N. Arnold, Inna Georgieva, Harald Stein, Martin Zeitz, Peter T. Daniel, Isrid Sturm
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are classified by the WHO, yet its prognostic value needs to be confirmed. Therefore, we aimed to determine the prognostic role of cell cycle key regulatory genes p53, p27kip1 (p27), and cyclin E in this tumor entity. Experimental Design: Tumor specimen from 89 patients with a complete follow-up were studied immunohistochemically for p27 and cyclin E expression and for p53 mutations. The functional relevance of p27 was evaluated in the neuroendocrine cell lines BON1 (human) and INS1 (rat) by the use of small interfering RNA. Results: Twenty-six of 29 benign, well-differentiated endocrine tumors (WHO class 1) showed a high expression (&amp;gt;50%) of p27, whereas all 10 poorly differentiated endocrine carcinomas (WHO class 3) displayed a low expression of p27. Metastatic well-differentiated endocrine carcinomas (WHO class 2) showed a low p27 expression in 20 of 50 (40%) patients, which conferred a poor prognosis (median survival, 57 versus 140 months; P = 0.037). This prognostic dichotomy was improved by the use of a combination of p27 and cyclin E (high cyclin E/low p27 versus low cyclin E/high p27: median survival 53 months versus not reached; P = 0.0044). p53 mutations were rare (1 of 10 poorly differentiated endocrine carcinomas). Conclusions: Loss of p27 and overexpression of cyclin E play a critical role in the aggressiveness of gastroenteropancreatic neuroendocrine tumors. This coincides with increased cell cycle progression. We propose a discussion whether to incorporate the immunohistochemical expression of p27 into a revised classification to individualize therapeutic strategies in this tumor entity.
Vascular Endothelial Growth Factor Upregulates the Expression of Matrix Metalloproteinases in Vascular Smooth Muscle Cells
Authors: He Wang, Joan A. Keiser
Journal: Circulation Research (1998)

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis that stimulates proliferation, migration, and proteolytic activity of endothelial cells. Although the mitogenic activity of VEGF is endothelial cell specific, recent reports indicate VEGF is able to stimulate chemotaxis and tissue factor production in monocytes. VEGF-stimulated activity in monocytes is mediated by the VEGF receptor flt-1. The purpose of the present study was to investigate the effects of VEGF on another major cell type in the vascular wall, namely, the vascular smooth muscle cell (SMC). Using cultured cells, we showed that VEGF has a minimal mitogenic effect on SMCs, which is in accordance with published data. However, VEGF treatment significantly enhanced production of matrix metalloproteinase (MMP)-1, -3, and -9 by human SMCs. The upregulation of MMP-1 and MMP-9 was pronounced, and the stimulation for MMP-3 was less prominent. Stimulation could be demonstrated at both protein and mRNA levels, as reflected by ELISA, zymography, and Northern blot analysis. To explore the signal transduction pathway for the effect of VEGF on SMCs, we studied the expression of 2 high-affinity VEGF receptors, the kinase insert domain-containing receptor (KDR) and flt-1, in human SMCs. Both reverse transcriptase-polymerase chain reaction and immunoblotting revealed the expression of flt-1. Immunoprecipitation followed by immunoblotting illustrated phosphorylation of the flt-1 receptor after VEGF treatment. Similar methodology failed to detect expression of KDR in human SMCs. These data suggest the role of flt-1 in mediating VEGF-stimulated MMP expression of SMCs. The physiological relevance of MMP upregulation was studied by examining VEGF-stimulated SMC migration through 2 synthetic extracellular matrix barriers, Matrigel and Vitrogen. Our results indicate that VEGF treatment accelerated SMC migration through both barriers, and that this response was blocked by MMP inhibition in Matrigel, which supports a permissive role of MMP in SMC migration. These data are the first to show a direct effect of VEGF on SMCs. SMC-derived MMPs may be an additional source of proteases to digest vascular basement membrane, which is a crucial step in the initial stage of angiogenesis. The MMPs may also contribute to SMC migration in angiogenesis and atherogenesis.
Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates
Authors: Anna Glantz, Hanns-Ulrich Marschall, Lars-Åke Mattsson
Journal: Hepatology (2004)

Intrahepatic cholestasis of pregnancy (ICP), characterized by pruritus in the second half of pregnancy, entails an increased risk to the fetus. This study was designed to determine the incidence and fetal complication rates in ICP, and to define groups at increased risk. In an prospective cohort study conducted between February 1, 1999, and January 31, 2002, all 45,485 pregnancies in a defined region of Sweden (Västra Götaland) were screened for ICP, defined as otherwise unexplained pruritus of pregnancy in combination with fasting serum bile acid levels > or = 10 micromol/L. Pruritus was reported by 937 (2.1%) women, and ICP was diagnosed in 693 (1.5%). Simple logistic regression analyses showed that the probability of fetal complications (spontaneous preterm deliveries, asphyxial events, and meconium staining of amniotic fluid, placenta, and membranes) increased by 1%-2% per additional micromol/L of serum bile acids. Complementary analyses showed that fetal complications did not arise until bile acid levels were > or = 40 micromol/L. Gallstone disease and a family history of ICP were significantly (P < .001) more prevalent in the group of ICP patients with higher bile acid levels. In conclusion, we found an incidence of ICP in our population of 1.5%. From complication rates recorded prospectively, we could define a mild (81%) and a severe (19%) form of ICP, the latter with bile acid levels > or = 40 micromol/L. No increase in fetal risk was detected in ICP patients with bile acid levels < 40 micromol/L, and we propose that these women be managed expectantly, which would significantly reduce the costs of medical care.
Current Status of Cardiac Transplantation
Authors: Sharon A. Hunt
Journal: JAMA (1998)

Cardiac transplantation, first introduced 30 years ago, has become a widely used and increasingly important procedure for treatment of truly end-stage heart disease. Current use is limited strictly by donor supply, making selection of appropriate recipients an important ethical and societal issue. Survival rates after transplantation rose in the 1980s with the use of cyclosporine and have remained relatively consistent since then, although recipients older than 65 years or younger than 1 year have lower survival rates than recipients of other ages. Although immunosuppressive drugs have helped establish cardiac transplantation as a successful procedure, risks of opportunistic infection and rejection, as well as coronary arteriopathy, have led to development of new immunosuppressive agents currently under study. Future alternatives to the current technology of cardiac allotransplantation may include xenotransplantation and/or nonbiological replacement of the heart with mechanical devices.
Dialectical Behavior Therapy Compared With General Psychiatric Management for Borderline Personality Disorder: Clinical Outcomes and Functioning Over a 2-Year Follow-Up
Authors: Shelley F. McMain, Tim Guimond, David L. Streiner, Robert J. Cardish, Paul S. Links
Journal: American Journal of Psychiatry (2012)

The authors conducted a 2-year prospective naturalistic follow-up study to evaluate posttreatment clinical outcomes in outpatients who were randomly selected to receive 1 year of either dialectical behavior therapy or general psychiatric management for borderline personality disorder.Patients were assessed by blind raters 6, 12, 18, and 24 months after treatment. The clinical effectiveness of treatment was assessed on measures of suicidal and nonsuicidal self-injurious behaviors, health care utilization, general symptom distress, depression, anger, quality of life, social adjustment, borderline psychopathology, and diagnostic status. The authors conducted between-group comparisons using generalized estimating equation, mixed-effects models, or chi-square statistics, depending on the distribution and nature of the data.Both treatment groups showed similar and statistically significant improvements on the majority of outcomes 2 years after discharge. The original effects of treatment did not diminish for any outcome domain, including suicidal and nonsuicidal self-injurious behaviors. Further improvements were seen on measures of depression, interpersonal functioning, and anger. However, even though two-thirds of the participants achieved diagnostic remission and significant increases in quality of life, 53% were neither employed nor in school, and 39% were receiving psychiatric disability support after 36 months.One year of either dialectical behavior therapy or general psychiatric management was associated with long-lasting positive effects across a broad range of outcomes. Despite the benefits of these specific treatments, one important finding that replicates previous research is that participants continued to exhibit high levels of functional impairment. The effectiveness of adjunctive rehabilitation strategies to improve general functioning deserves additional study.
The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial
Authors: Anthony G Marson, Asya M Al-Kharusi, Muna Alwaidh, Richard Appleton, Gus A Baker, David W Chadwick, Celia Cramp, Oliver C Cockerell, Paul N Cooper, Julie Doughty, Barbara Eaton, Carrol Gamble, Peter J Goulding, Stephen JL Howell, Adrian Hughes, Margaret Jackson, Ann Jacoby, Mark Kellett, Geoffrey R Lawson, John Paul Leach, Paola Nicolaides, Richard Roberts, Phil Shackley, Jing Shen, David F Smith, Philip EM Smith, Catrin Tudur Smith, Alessandra Vanoli, Paula R Williamson
Journal: The Lancet (2007)
Combination of theophylline and prostaglandin E1 as inhibitors of the adjuvant-induced arthritis syndrome of rats.
Authors: I.L Bonta, M.J Parnham, L Van Vliet
Journal: Annals of the Rheumatic Diseases (1978)

The effects of daily subcutaneous administration of prostaglandin E1 (PGE1), theophylline, and of both drugs together were studied on the Freund9s adjuvant-induced inflammatory and arthritic syndrome in rats. In the doses used, neither drug affected the acute inflammatory response in the adjuvant-treated paw, but together they caused marked inhibition. Chronic inflammation in the contralateral (nontreated) hind paws was slightly inhibited by each drug and combined treatment resulted in marked inhibition. The drugs also counteracted splenomegaly in adjuvant-diseased rats and their effects on spleen weight paralleled the inhibition of chronic inflammation. Arthritic lesions, as judged by x-rays of tibiotarsal joint destruction in the nontreated paws, were partially prevented by PGE1 alone, but not by theophylline. The combined treatment entirely prevented these joint lesions. PGE1 did not cause an increase in adrenal weight, but enhanced the effect of theophylline on adrenal weight. Only PGE1 improved gait in arthritic rats, simultaneous theophylline treatement having little additional effect. Other workers have found the PGE1 increases intracellular cAMP and that this effect is enhanced by the phosphodiesterase inhibitor, theophylline. We propose that the anti-inflammatory and anti-arthritic effects of combined drug treatment involve cAMP changes in phagocytic cells at the site of tissue injury and in systemic lymphocytes.
Phase I Clinical and Pharmacokinetic Evaluation of the Vascular-Disrupting Agent OXi4503 in Patients with Advanced Solid Tumors
Authors: Dan M. Patterson, Martin Zweifel, Mark R. Middleton, Patricia M. Price, Lisa K. Folkes, Michael R.L. Stratford, Phil Ross, Sarah Halford, Jane Peters, Jai Balkissoon, Dai J. Chaplin, Anwar R. Padhani, Gordon J.S. Rustin
Journal: Clinical Cancer Research (2012)

Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents.Escalating doses of OXi4503 were given intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors.Doses were escalated in single-patient cohorts from 0.06 to 1.92 mg/m(2), then expanded cohorts to 15.4 mg/m(2) in 43 patients. Common adverse drug reactions were hypertension, tumor pain, anemia, lymphopenia, and easily controllable nausea/vomiting and fatigue. Five patients experienced different drug-related dose-limiting toxicities, atrial fibrillation, increased troponin, blurred vision, diplopia, and tumor lysis. Prophylactic amlodipine failed to prevent adverse events. Pharmacokinetics showed dose-dependent linear increases in peak plasma concentrations and area under the curve value of OXi4503. One partial response was seen in a heavily pretreated patient with ovarian cancer. Dynamic contrast-enhanced MRI confirmed a dose effect and showed significant antivascular effects in 10 of 13 patients treated at doses of 11 mg/m(2) or higher.The maximum tolerated dose was 8.5 mg/m(2) but escalation to 14 mg/m(2) was possible with only temporary reversible cerebrovascular toxicity by excluding hypertensive patients. As a tumor response was seen at 14 mg/m(2) and maximum tumor perfusion reductions were seen at doses of 11 mg/m(2) or higher, the recommended phase II dose is from 11 to 14 mg/m(2).
Myelodysplastic Syndromes in Patients Younger Than Age 50
Authors: Andrea Kuendgen, Corinna Strupp, Manuel Aivado, Barbara Hildebrandt, Rainer Haas, Norbert Gattermann, Ulrich Germing
Journal: Journal of Clinical Oncology (2006)

Myelodysplastic syndromes (MDS) mainly occur in the elderly but can affect younger individuals too. The latter require special consideration to identify suitable candidates for allogeneic stem-cell transplantation, a potentially curative approach carrying a high risk of treatment-related complications.We report the largest series of young MDS patients as yet, including 232 patients younger than 50 years. Their clinical characteristics and prognosis are compared with 2,496 patients older than 50 years.Survival was significantly longer in the younger versus older age group (40 v 23 months, respectively; P < .00005). The difference arose from patients belonging to the low- and intermediate-I-risk categories of the International Prognostic Scoring System (median survival not reached v 45 months, respectively; P < .00005). In contrast, survival was identical for both age groups (8 months for both younger and older patients; P = .81) in the intermediate-II-and high-risk categories. Established classification systems and risk scores were applicable to young patients with primary MDS. Interestingly, a particularly large difference in median survival time was seen between the intermediate-I-and intermediate-II-risk groups (176 v 8 months, respectively). For low-risk patients, the overall survival rate was more than 86% at 20 years.According to these results, aggressive treatment approaches should rarely be recommended to younger MDS patients belonging to the low and intermediate-I risk groups.
Guidelines for Human Epidermal Growth Factor Receptor 2 Testing: Biologic and Methodologic Considerations
Authors: Guido Sauter, James Lee, John M.S. Bartlett, Dennis J. Slamon, Michael F. Press
Journal: Journal of Clinical Oncology (2009)

The goal of this review is to systematically address a number of issues raised in the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines on testing for the human epidermal growth factor receptor 2 (HER-2) alteration. A group of investigators who are experienced in the conduct and interpretation of HER-2 assay methods reviewed the ASCO-CAP guidelines and address several areas of the HER-2 testing guidelines with a particular emphasis on biologic and methodologic considerations. Although HER-2 status determined by immunohistochemistry (IHC) and the status determined by fluorescent in situ hybridization (FISH) are significantly correlated, we feel that standard considerations of laboratory testing, including test accuracy, reproducibility, and precision, as well as the current data favor FISH over IHC assay methods for determining HER-2 status. These considerations are clearly important in clinical practice because HER2 amplification is directly linked to protein expression levels in breast cancer. However, this protein is not consistently analyzed in formalin-fixed tissues as a result of variability in fixation methods and times and the impact of fixation on HER-2 protein antigenicity. Conversely, gene amplification and FISH are significantly less dependent on tissue fixation methods, making this assay more reproducible between central and peripheral laboratories than IHC. Moreover, review of the existing data demonstrate that FISH is more strongly correlated with responsiveness to either trastuzumab or lapatinib treatment. Until other methods achieve similar test accuracy, reproducibility, and predictive value, we suggest FISH as the primary HER-2 testing modality for women with breast cancer who are candidates for HER-2-targeted therapies.
Anergic T cells exert antigen-independent inhibition of cell-cell interactions via chemokine metabolism
Authors: Martha J. James, Lavina Belaramani, Kanella Prodromidou, Arpita Datta, Sussan Nourshargh, Giovanna Lombardi, Julian Dyson, Diane Scott, Elizabeth Simpson, Lorraine Cardozo, Anthony Warrens, Richard M. Szydlo, Robert I. Lechler, Federica M. Marelli-Berg
Journal: Blood (2003)
Adult intracranial WHO grade II ependymomas: long-term outcome and prognostic factor analysis in a series of 114 patients
Authors: P. Metellus, J. Guyotat, O. Chinot, A. Durand, M. Barrie, R. Giorgi, A. Jouvet, D. Figarella-Branger
Journal: Neuro-Oncology (2010)

Ependymomas account for 2% of all intracranial tumors in adults. Considerable controversy continues to exist with regard to their prognostic factors and therapeutic management due to the rarity and the heterogeneity of series reported so far. The authors report a retrospective study of a homogenous population of 114 adult patients harboring WHO grade II intracranial ependymomas from 32 French Neurosurgical Centers between 1990 and 2004. All clinico-radiological and follow-up data were analyzed, and a central pathologic review was performed by two confirmed neuropathologists. The 5- and 10-year overall survival (OS) rates were 86.1% and 81.0%, respectively; the 5- and 10-year progression-free survival (PFS) rates were 74.6% and 58.9%, respectively. On multivariate analysis, the OS rates were associated with preoperative KPS score (P = .027), extent of surgery (P = .008), and tumor location (supratentorial vs infratentorial, P = .012). The multivariate analysis also revealed that the risk of recurrence was associated with incomplete resection (P = .001) and supratentotrial location (P = .038). Moreover, adjuvant radiotherapy (RT) for patients with incompletely resected tumors is responsible for a significant improvement of both overall (P = .005) and progression-free (P = .002) survival. This study clearly supports the major prognostic impact of the extent of surgery in WHO grade II. Interestingly, tumor location also seems to have an actual impact on both OS and PFS. Finally, the prognostic impact of RT was found to be beneficial for incompletely resected tumors.
More targeted screening is necessary but may face resistance, experts say
Authors: A. O'Dowd
Journal: BMJ (2014)

Changes to make national screening programmes more targeted at people with a higher risk of developing conditions and diseases may be unpopular with the general public, experts have told MPs.

Witnesses at a 25 June evidence session of the House of Commons science and technology committee’s inquiry into national health screening said that changes were needed but that they might not be universally welcomed.

MPs asked how difficult it would be to introduce more targeted, stratified screening if the general public was concerned that not everyone would be screened—possibly failing to detect problems in some people.

Hilary Burton, director of the PHG Foundation, an independent think tank focusing on genomics and other emerging …
Severity of Autonomic and Sensory Neuropathy and the Impairment of Visual- and Auditory-Evoked Potentials in Type 1 Diabetes
Authors: Tamás T. Várkonyi, Éva Börcsök, Ferenc Tóth, Zsuzsanna Fülöp, Róbert Takács, László Rovó, Csaba Lengyel, József Géza Kiss, Márta Janáky, Zsolt Hermányi, Péter Kempler, János Lonovics
Journal: Diabetes Care (2006)

It became clear in the last decades that neuropathy is not a separate clinical entity, but a component of several related complications (1). Although the functional consequences of neuropathy are well defined in various organ systems, the relationship of the alterations in the networks of the neuronal system is still poorly documented. Assessment of the potential common alterations of the different neuronal functions in patients with diabetic neuropathy may provide new pathogenetic and diagnostic considerations. Previously, we observed correlations between the delay of certain auditory-evoked potentials and the severity of autonomic and peripheral sensory neuropathy in patients with type 1 diabetes (2). In addition, we found a relationship between the latency of visual-evoked potentials and the peripheral neuronal function (3). The aims of this study were to analyze the possible correlations between the central auditory and visual afferentations and the severity of autonomic and sensory neuropathy in patients with long-standing type 1 diabetes.

A total of 10 middle-aged type 1 diabetic patients …