tbuckley/cabot-search huggingface dataset:
Regulatory CD25+ T Cells in Human Kidney Transplant Recipients
Authors: Alan D. Salama, Nader Najafian, Michael R. Clarkson, William E. Harmon, Mohamed H. Sayegh
Journal: Journal of the American Society of Nephrology (2003)

Recent evidence suggests that a population of professional regulatory cells, which limit immune responsiveness, exist in rodents and healthy human subjects. However, their role in disease states remains unclear. A proportion of renal transplant recipients do not demonstrate in vitro reactivity toward their mismatched donor-derived HLA-DR antigens; it was therefore hypothesized that this may be due to such regulatory cells. A cohort of 23 renal transplant recipients was studied at a single institution. In patients with no history of acute rejection, 6 (40%) of 15 demonstrated regulation toward the mismatched HLA-DR allopeptides by CD25(+) cells. By contrast, only one (12.5%) in eight of those with a history of acute rejection demonstrated regulation. Interestingly, if the patient assays were stratified according to initial in vitro immune responsiveness toward the mismatched allopeptides, 8 (47.1%) of 17 of patient assays with low allopeptide responsiveness (alloreactive T cell frequencies less than 60/million) demonstrated regulation of indirect pathway alloresponses by CD25(+) cells, whereas 0 of 8 with higher responses (frequencies greater than 60/million) demonstrated no such regulation (P < 0.05 by chi(2) test). The regulatory cells are present in the circulation as early as 3 mo after transplantation and persist for a number of years, despite conventional immunosuppression. Furthermore, induction treatment with anti-IL-2R mAb did not prevent the development of these regulatory CD25(+) cells. Data from two patients suggest that these cells may also play a role in preventing epitope shifting, implicated in the ongoing immune activation contributing to chronic rejection, and that loss of regulation in a given patient may precede an episode of rejection.
Results of the Brazilian Osteosarcoma Treatment Group Studies III and IV: Prognostic Factors and Impact on Survival
Authors: A. Sérgio Petrilli, Beatriz de Camargo, Vicente Odone Filho, Paula Bruniera, Algemir L. Brunetto, Reynaldo Jesus-Garcia, Olavo P. Camargo, Walter Pena, Pedro Péricles, Alexandre Davi, José D. Prospero, Maria Teresa S. Alves, Claudia R. Oliveira, Carla R.D. Macedo, Wellington L. Mendes, Maria Teresa A. Almeida, Maria L. Borsato, Telma M. dos Santos, Jorge Ortega, Elio Consentino
Journal: Journal of Clinical Oncology (2006)

Purpose To evaluate the impact of chemotherapy and surgery on the outcome of osteosarcoma (OS) of the extremities and to identify prognostic factors in Brazilian patients. Patients and Methods A total of 225 patients with metastatic and nonmetastatic OS of the extremities were enrolled and assessed in two consecutive studies designed and implemented by the Brazilian Osteosarcoma Treatment Group. Results The 5-year survival and event-free survival rates for the 209 assessable patients were 50.1% and 39%, respectively; for the 178 patients with nonmetastatic disease at diagnosis, the rates were 60.5% and 45.5%, respectively. The multivariate analysis showed that the following variables were associated with a shorter survival: metastases at diagnosis (P &lt; .001), necrosis grades 1 and 2 (P = .046), and tumor size (P = .0071). Conclusion The overall 5- and 10-year survival rates were lower than the rates reported in North American and European trials. A pattern of advanced disease at diagnosis was often present, with a high proportion of patients having metastases (20.8%) and large tumor size (42.9%). However, these features were not necessarily associated with longer duration of prediagnostic symptoms. These findings were considered in the strategic planning of the current Brazilian cooperative study, with the aim of improving survival and quality of life of a large number of patients with OS.
Physical Activity and Survival After Colorectal Cancer Diagnosis
Authors: Jeffrey A. Meyerhardt, Edward L. Giovannucci, Michelle D. Holmes, Andrew T. Chan, Jennifer A. Chan, Graham A. Colditz, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2006)

Physically active individuals have a lower risk of developing colorectal cancer but the influence of exercise on cancer survival is unknown.By a prospective, observational study of 573 women with stage I to III colorectal cancer, we studied colorectal cancer-specific and overall mortality according to predefined physical activity categories before and after diagnosis and by change in activity after diagnosis. To minimize bias by occult recurrences, we excluded women who died within 6 months of their postdiagnosis physical activity assessment.Increasing levels of exercise after diagnosis of nonmetastatic colorectal cancer reduced cancer-specific mortality (P for trend = .008) and overall mortality (P for trend = .003). Compared with women who engaged in less than 3 metabolic equivalent task [MET] -hours per week of physical activity, those engaging in at least 18 MET-hours per week had an adjusted hazard ratio for colorectal cancer-specific mortality of 0.39 (95% CI, 0.18 to 0.82) and an adjusted hazard ratio for overall mortality of 0.43 (95% CI, 0.25 to 0.74). These results remained unchanged even after excluding women who died within 12 and 24 months of activity assessment. Prediagnosis physical activity was not predictive of mortality. Women who increased their activity (when comparing prediagnosis to postdiagnosis values) had a hazard ratio of 0.48 (95% CI, 0.24 to 0.97) for colorectal cancer deaths and a hazard ratio of 0.51 (95% CI, 0.30 to 0.85) for any-cause death, compared with those with no change in activity.Recreational physical activity after the diagnosis of stages I to III colorectal cancer may reduce the risk of colorectal cancer-specific and overall mortality.
A Bayesian Approach to a Patient With a Residual Mass After Treatment for Non-Hodgkin's Lymphoma of the Thyroid
Authors: John Bibb, Robert Hromas, Ian Rabinowitz
Journal: Journal of Clinical Oncology (2005)

A 51-year-old female with a previous history of Hashimoto’s disease presented with a right neck mass. The mass was thought to involve the thyroid gland. An initial fine needle aspirate was nondiagnostic, but suspicious for lymphoma. An open incisional biopsy of the thyroid mass revealed a diffuse large B-cell lymphoma and surrounding thyroid parenchyma revealing chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis). The large neoplastic lymphoid cells were strongly CD 20 positive on immunohistochemical staining. Flow cytometry revealed that 15% of the cells were abnormal B-lymphocytes with CD 19, CD20, FMC7 expression and loss of immunoglobulin lightchain expression, consistent with a B-cell lymphoma. A computed tomography scan revealed a 3 5 cm mass that involved the thyroid as well as a 1 2 cm right supraclavicular node. A staging work-up, including a positron emission tomography (PET) scan and a bone marrow biopsy, determined that she apparently had disease localized to the neck, with only the thyroid mass and the supraclavicular node demonstrating fluorodeoxyglucose (FDG) uptake. She was treated with four cycles of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab, followed by involved-field radiation to the neck (41.40 Gy). After completion of this therapy, a firm, nontender 1.5 cm mass was still present in the right thyroid region. A repeat PET scan, performed approximately 6 weeks after the completion of the radiation, demonstrated that the thyroid mass had shrunk from 5 cm to 1.5 cm and that the supraclavicular node had disappeared. The thyroid mass was still avid for FDG uptake; no other areas of abnormality were noted. A presumptive diagnosis of residual lymphoma was made and the patient was scheduled to be admitted for reinduction chemotherapy to be followed by high-dose chemotherapy with autologous stem-cell support.
Histologic and Dynamic Changes Induced by Chronic Metabolic Acidosis in the Rat Growth Plate
Authors: Eduardo Carbajo, José Manuel López, Fernando Santos, Flor Angel Ordóñez, Pilar Niño, Julián Rodríguez
Journal: Journal of the American Society of Nephrology (2001)

Abstract. To understand better the pathophysiology of growth impairment in persistent metabolic acidosis, the morphology and dynamics of the growth plate were studied in young rats grouped as follows: rats that were made acidotic by oral administration of ammonium chloride for 14 d (AC), nonacidotic rats that were fed ad libitum (control [C]), and nonacidotic rats that were pair-fed with the AC group (PF). AC rats became markedly acidotic and growth retarded. The volume of newly formed bone per day (mean ± SEM) was significantly lowered (P < 0.05) in AC rats (AC, 3.4 ± 0.4; C, 8.4 ± 0.6; PF, 6.4 ± 0.5 mm3/d). Growth plate height was lower in AC rats (303.8 ± 12.7 μm) than in either C (478.0 ± 16.0 μm) or PF rats (439.0 ± 21.4 μm). The processes of chondrocyte proliferation (assessed by bromodeoxyuridine labeling) and maturation (assessed by stereologic estimators of size and shape of chondrocytes and the volume of matrix per cell) were not impaired by acidosis. By contrast, the dynamics of hypertrophic chondrocytes were altered significantly: both cell turnover per column per day (AC, 4.4 ± 0.4; C, 8.0 ± 0.8; PF, 6.2 ± 0.6) and linear velocity of advance of chondrocytes (AC, 5.7 ± 0.5; C, 11.2 ± 0.9; PF, 9.4 ± 0.8 μm/h) were lowered significantly. The study presented here shows the inhibitory effect of metabolic acidosis on cartilage cell progression and endochondral bone formation. Finally, the data show that metabolic acidosis caused a marked shortening of the growth plate because chondrocyte turnover was affected to a greater extent than bone tissue formation.
Better Survival With Interleukin-2-Based Regimens? Possibly Only in Highly Selected Patients
Authors: Sylvie Négrier
Journal: Journal of Clinical Oncology (2004)

In this issue of the Journal of Clinical Oncology, Atzpodien et al 1 report interesting but surprising results of a randomized multicenter trial of chemoimmunotherapy in patients with metastatic renal carcinoma.Patients were randomly assigned to receive either a triple combination of subcutaneous interleukin-2 (IL-2) and interferon (IFN) with IV fluorouracil (FU), or the same combination combined with oral 13-cis-retinoic acid (po-13cRA); the control group was treated with IFN combined with vinblastine.The response rates, which were the primary end point of the study, were not different among the treatment groups.Both combinations of FU, IL-2, and IFN, with or without po-13cRA, demonstrated a survival advantage compared with the control arm; the largest difference was seen with FU, IL-2, IFN, and po-13cRA.By the survival curves, the largest differences in survival seem to occur about 1 year after treatment starts, but these differences dramatically diminish after 4 to 5 years.These results are surprising for several reasons.First, it is not often that treatments of metastatic cancer lead to an advantage in patient survival without a significant difference in response rates.3][4][5] This observation is important because the demonstration of a survival gain without significant improvement of response rates means that the main treatment effect is more likely due to tumor growth inhibition than to tumor reduction.Such an effect is generally expected from treatments administered over a prolonged period of time and also from treatments that are mainly active through blocking mechanisms of tumor growth factors.These are not the usual mechanisms of action identified with IL-2 and FU, which seem to be the most important components in these combinations.The median duration of treatments was 2.2 months, which is rather short.Moreover, other authors
Acid hydrolases in blister fluid.
Authors: GUNNAR VOLDEN
Journal: British Journal of Dermatology (1978)

Cathepsin B1 and Cathepsin C have been characterized and quantifled in suction blister fluid. These enzymes revealed practically no activity in interstitial fluid and serum. Arylamidase was also investigated and found to have similar concentrations in serum, blister fluid and interstitial fluid. The properties of arylamidase from these sources were identical.
Novel two mechanisms for acquired EGFR-TKI resistance in lung cancer cells harboring EGFR activating mutation
Authors: Hiroto Izumi, Rina Kanda, Yuichi Murakami, Yasuo Morimoto, Mayumi Ono
Journal: European Respiratory Journal (2014)

EGF receptor (EGFR) tyrosine kinase inhibitors, including gefitinib and erlotinib, exert potent therapeutic efficacy in non-small cell lung cancers (NSCLC) harboring EGFR-activating mutations. However, most patients ultimately develop resistance to these drugs. Here, we report two kinds of mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors. In this study, we established gefitinib or erlotinib-resistant NSCLC cells from PC-9 cell line harboring del EGFR mutation. In gefitinib-resistant lung cancer cells, they showed a marked downregulation of PTEN expression and increased Akt phosphorylation. Knockdown of PTEN expression using small interfering RNA specific for PTEN in PC-9 cells resulted in drug resistance to gefitinib and erlotinib. Reduced PTEN expression was also observed in tumor samples from patients with gefitinib-refractory NSCLC. On the other hand, in erlotinib-resistant lung cancer cells, they showed marked expressions of Src, integrin beta 1, alpha 2, and alpha 5 along with enhanced cell adhesion activity. RNAi-mediated silencing of integrin beta 1 restored erlotinib sensitivity and reduced activation of Src and Akt after erlotinib treatment. Increased expression of integrin beta 1, alpha 5, and/or alpha 2 was also observed in tumor samples from patients with lung cancer treated with erlotinib and/or gefitinib. Together, we present our novel two mechanisms, PTEN loss and integrin beta 1/Src activation, involving acquired resistance to EGFR TKI in lung cancer cells. Our findings suggested that acquired Akt activation by a variety of ways contributes to gefitinib and erlotinib resistance in NSCLC.
Clonal Expression of the Tn Antigen in Erythroid and Granulocyte Colonies and Its Application to Determination of the Clonality of the Human Megakaryocyte Colony Assay
Authors: William Vainchenker, Ugo Testa, Jeanne Françoise Deschamps, Annie Henri, Monique Titeux, Janine Breton-Gorius, Henri Rochant, Douglas Lee, Jean-Pierre Cartron
Journal: Journal of Clinical Investigation (1982)

To evaluate whether exposure of Tn determinants at the surface of human erythrocytes, platelets, and granulocytes could arise from a somatic mutation in a hemopoietic stem cell, burst-forming unit erythroid (BFU-E) colonies, colony-forming unit granulocyte-macrophage (CFU-GM), and colony-forming unit-eosinophil (CFU-Eo) were grown from a blood group O patient with a typical Tn syndrome displaying two distinct populations (Tn+ and Tn-) of platelets, granulocytes, and erythrocytes. A large number of colonies was observed. Individual colonies were studied with a fluorescent conjugate of Helix pomatia agglutinin (HPA). A sizeable fraction of each of the erythroid and granulocytic colonies appeared to consist exclusively of either HPA-positive or HPA-negative cells, thereby demonstrating the clonal origin of those exhibiting the Tn marker. Similar results were obtained from a second patient. These findings establish that the HPA labeling of Tn cells is an accurate marker permitting assessment of the clonality of the human megakaryocyte (MK) colony assay. For the study of MK cultures a double-staining procedure using the HPA lectin and a monoclonal antiplatelet antibody (J-15) was applied in situ to identify all MK constituting a colony. Our results, obtained in studies of 133 MK colonies, provide definitive evidence that the human MK colony assay is clonal because all MK colonies were exclusively composed of Tn+ and Tn- MK. Furthermore, the distribution of MK within a single colony was shown to be seminormal with a mean at 6 MK, isolated MK typically being absent in culture.
Constructing the cerebral cortex: Neurogenesis and fate determination
Authors: Susan K. McConnell
Journal: Neuron (1995)

Sitting at the apex of neural processing in the mammalian brain is the cerebral cortex, the convoluted sheet of neurons covering the two cerebral hemispheres. Neurons within the neocortex underlie our most sophisticated cognitive and perceptual abilities and are thus highly specialized for the analysis of sensory inputs or the generation of motor outputs. The position, connectivity, and morphology of each neuron reflect its particular function. Although neurons in the adult brain are organized in highly ordered and differentiated arrays, these cells arise from dividing progenitor cells of a simple neuroepithelium in which cells appear morphologically indistinguishable. This review addresses the question of how diverse neuronal phenotypes are generated from apparently homogeneous progenitors in appropriate numbers, times, and positions during the development of the cerebral cortex, focusing on key steps in neurogenesis including the molecular control of cell number, the decision to generate a neuron, and cell type specification. Overview of Cortical Organization and Development
A Meta-Analytic Review of Psychosocial Interventions for Substance Use Disorders
Authors: Lissa Dutra, Georgia Stathopoulou, Shawnee L. Basden, Teresa M. Leyro, Mark B. Powers, Michael W. Otto
Journal: American Journal of Psychiatry (2008)

Despite significant advances in psychosocial treatments for substance use disorders, the relative success of these approaches has not been well documented. In this meta-analysis, the authors provide effect sizes for various types of psychosocial treatments, as well as abstinence and treatment-retention rates for cannabis, cocaine, opiate, and polysubstance abuse and dependence treatment trials.With a comprehensive series of literature searches, the authors identified a total of 34 well-controlled treatment conditions-five for cannabis, nine for cocaine, seven for opiate, and 13 for polysubstance users-representing the treatment of 2,340 patients. Psychosocial treatments evaluated included contingency management, relapse prevention, general cognitive behavior therapy, and treatments combining cognitive behavior therapy and contingency management.Overall, controlled trial data suggest that psychosocial treatments provide benefits reflecting a moderate effect size according to Cohen's standards. These interventions were most efficacious for cannabis use and least efficacious for polysubstance use. The strongest effect was found for contingency management interventions. Approximately one-third of participants across all psychosocial treatments dropped out before treatment completion compared to 44.6% for the control conditions.Effect sizes for psychosocial treatments for illicit drugs ranged from the low-moderate to high-moderate range, depending on the substance disorder and treatment under study. Given the long-term social, emotional, and cognitive impairments associated with substance use disorders, these effect sizes are noteworthy and comparable to those for other efficacious treatments in psychiatry.
Effects of Sustained Antiangiogenic Therapy in Multistage Prostate Cancer in TRAMP Model
Authors: Tatyana Isayeva, Diptiman Chanda, Lisa Kallman, Isam-Eldin A. Eltoum, Selvarangan Ponnazhagan
Journal: Cancer Research (2007)

Abstract Antiangiogenic therapy is a promising alternative for prostate cancer growth and metastasis and holds great promise as an adjuvant therapy. The present study evaluated the potential of stable expression of angiostatin and endostatin before the onset of neoplasia and during the early and late stages of prostate cancer progression in transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Groups of 5-, 10-, and 18-week-old male TRAMP mice received recombinant adeno-associated virus-6 encoding mouse endostatin plus angiostatin (E+A) by i.m. injection. The effects of therapy were determined by sacrificing groups of treated mice at defined stages of tumor progression and following cohorts of similarly treated mice for long-term survival. Results indicated remarkable survival after recombinant adeno-associated virus–(E+A) therapy only when the treatment was given at an earlier time, before the onset of high-grade neoplasia, compared with treatment given for invasive cancer. Interestingly, early-stage antiangiogenic therapy arrested the progression of moderately differentiated carcinoma to poorly differentiated state and distant metastasis. Immunohistochemical analysis of the prostate from treated mice indicated significantly lower endothelial cell proliferation and increased tumor cell apoptosis. Vascular endothelial growth factor receptor (VEGFR)-2 expression was significantly down-regulated in tumor endothelium after treatment but not VEGFR-1. Analysis of the neuroendocrine marker synaptophysin expression indicated that antiangiogenic therapy given at an early-stage disease reduced neuroendocrine transition of the epithelial tumors. These studies indicate that stable endostatin and angiostatin gene therapy may be more effective for minimally invasive tumors rather than advanced-stage disease. [Cancer Res 2007;67(12):5789–97]
Short-term associations between outdoor air pollution and visits to accident and emergency departments in London for respiratory complaints
Authors: RW Atkinson, HR Anderson, DP Strachan, JM Bland, SA Bremner, A Ponce de Leon
Journal: European Respiratory Journal (1999)

Many epidemiological studies have shown positive short-term associations between health and current levels of outdoor air pollution. The aim of this study was to investigate the association between air pollution and the number of visits to accident and emergency (A&amp;E) departments in London for respiratory complaints. A&amp;E visits include the less severe cases of acute respiratory disease and are unrestricted by bed availability. Daily counts of visits to 12 London A&amp;E departments for asthma, other respiratory complaints, and both combined for a number of age groups were constructed from manual registers of visits for the period 1992-1994. A Poisson regression allowing for seasonal patterns, meteorological conditions and influenza epidemics was used to assess the associations between the number of visits and six pollutants: nitrogen dioxide, ozone, sulphur dioxide, carbon monoxide, and particles measured as black smoke (BS) and particles with a median aerodynamic diameter of &lt;10 microm (PM10). After making an allowance for the multiplicity of tests, there remained strong associations between visits for all respiratory complaints and increases in SO2: a 2.8% (95% confidence interval (CI) 0.7-4.9) increase in the number of visits for a 18 microg x (-3) increase (10th-90th percentile range) and a 3.0% (95% CI 0.8-5.2) increase for a 31 microg x m(-3) increase in PM10. There were also significant associations between visits for asthma and SO2, NO2 and PM10. No significant associations between O3 and any of the respiratory complaints investigated were found. Because of the strong correlation between pollutants, it was difficult to identify a single pollutant responsible for the associations found in the analyses. This study suggests that the levels of air pollution currently experienced in London are linked to short-term increases in the number of people visiting accident and emergency departments with respiratory complaints.