tbuckley/cabot-search huggingface dataset:
Features of the Metabolic Syndrome Are Associated With Objectively Measured Physical Activity and Fitness in Danish Children
Authors: Søren Brage, Niels Wedderkopp, Ulf Ekelund, Paul W. Franks, Nicholas J. Wareham, Lars Bo Andersen, Karsten Froberg
Journal: Diabetes Care (2004)

OBJECTIVE—Features of the metabolic syndrome are becoming increasingly evident in children. Decreased physical activity is likely to be an important etiological factor, as shown previously for subjective measures of physical activity in selected groups. The purpose of this study was to examine the relationship between the metabolic syndrome and objectively measured physical activity and whether fitness modified this relationship. RESEARCH DESIGN AND METHODS—A total of 589 Danish children (310 girls, 279 boys, mean [±SD] age 9.6 ± 0.44 years, mean weight 33.6 ± 6.4 kg, mean height 1.39 ± 0.06 m) were randomly selected. Physical activity was measured with the uni-axial Computer Science &amp; Applications accelerometer (MTI actigraph) worn at the hip for at least 3 days (≥10 h/day) and fitness with a maximal bike test. As outcomes, we measured sitting systolic and diastolic blood pressure, degree of adiposity (sum of four skinfolds), and, finally, insulin, glucose, triglicerides, and HDL cholesterol in fasting blood samples. The outcome variables were statistically normalized and expressed as the number of SDs from the mean. (i.e., Z scores). A metabolic syndrome risk score was computed as the mean of these Z scores. Multiple linear regression was used to test the association between physical activity and metabolic risk, adjusted primarily for age, sex, sexual maturation, ethnicity, parental smoking, socioeconomic factors, and the Computer Science &amp; Applications unit, as well as for fitness. Robust SEs were computed by clustering on school. RESULTS—All children were in the nondiabetic range of fasting glucose. Metabolic risk was inversely related to physical activity (P = 0.008). The relationship was weakened after adjustment for fitness, but there was a significantly positive interaction between physical activity and fitness. CONCLUSIONS—Physical activity is inversely associated with metabolic risk, independently of potential confounders. The interaction between physical activity and fitness suggests that the potential beneficial effect of activity may be greatest in children with lower cardiorespiratory fitness.
Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs
Authors: Thordur Oskarsson, Swarnali Acharyya, Xiang H-F Zhang, Sakari Vanharanta, Sohail F Tavazoie, Patrick G Morris, Robert J Downey, Katia Manova-Todorova, Edi Brogi, Joan Massagué
Journal: Nature Medicine (2011)
Characterisation and manipulation of docetaxel resistant prostate cancer cell lines
Authors: Amanda J O'Neill, Maria Prencipe, Catherine Dowling, Yue Fan, Laoighse Mulrane, William M Gallagher, Darran O'Connor, Robert O'Connor, Aoife Devery, Claire Corcoran, Sweta Rani, Lorraine O'Driscoll, John M Fitzpatrick, R William G Watson
Journal: Molecular Cancer (2011)

There is no effective treatment strategy for advanced castration-resistant prostate cancer. Although Docetaxel (Taxotere®) represents the most active chemotherapeutic agent it only gives a modest survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel. Three Docetaxel resistant sub-lines were generated and confirmed to be resistant to the apoptotic and anti-proliferative effects of increasing concentrations of Docetaxel. The resistant DU-145 R and 22RV1 R had expression of P-glycoprotein and its inhibition with Elacridar partially and totally reversed the resistant phenotype in the two cell lines respectively, which was not seen in the PC-3 resistant sublines. Resistance was also not mediated in the PC-3 cells by cellular senescence or autophagy but multiple changes in pro- and anti-apoptotic genes and proteins were demonstrated. Even though there were lower basal levels of NF-κB activity in the PC-3 D12 cells compared to the Parental PC-3, docetaxel induced higher NF-κB activity and IκB phosphorylation at 3 and 6 hours with only minor changes in the DU-145 cells. Inhibition of NF-κB with the BAY 11-7082 inhibitor reversed the resistance to Docetaxel. This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-κB plays an immensely important role in determining docetaxel-resistance which may represent an appropriate therapeutic target.
Therapeutic Targeting of Nuclear Protein Import in Pathological Cell Conditions
Authors: Mirna N. Chahine, Grant N. Pierce
Journal: Pharmacological Reviews (2009)

Proteins enter the nucleus through the nuclear pore complex. Once in the nucleus, some proteins, such as transcriptional regulators, can turn genes on or off, and change the composition of the cell and its function to meet the demands of its environment. This process of protein import into the nucleus is highly controlled and regulated by the expression or function of single cargoes, transport receptors, or the transport channels themselves. Thus, these components of the import process have an impact on transport capacity, which subsequently affects gene expression, signal transduction, and cell growth and development. With such a key position in the process of cell growth, it is reasonable to hypothesize that alterations in nuclear protein transport may play an important role in pathological cell conditions that have abnormal cell growth as a central feature. Indeed, there are now sufficient data to demonstrate that alterations in nuclear protein transport participate in alterations in cell proliferation and hypertrophy. Further study is needed to provide definitive proof that changes in nuclear protein import directly participate in the pathogenesis of diseases such as hypertension, atherosclerosis, cancer, viral infection, and diabetes. However, the data to date have, on select occasions, led to a clear association of alterations in nuclear transport with disease states. Furthermore,this research has led to the important identification of new targets within the process of nuclear protein import that hold therapeutic promise to inhibit viral replication, to improve drug delivery during cancer therapy, and, in general, to modify cell growth and viability during disease conditions.
Lung involvement in Hodgkin's disease.
Authors: J B MacDonald
Journal: Thorax (1977)

Lung involvement occurred in 43% of 284 patients with Hodgkin9s disease in Nottingham during 1960-75. It was commoner than pleural, hilar or mediastinal node involvement, although over three-quarters of patients with any other thoracic manifestation subsequently developed pulmonary involvement. The patients with pulmonary involvement contained significantly fewer with the histological feature of lymphocyte predominance. The commonest radiographic type, peribronchial infiltration, tended to occur early in the course of the disease while less common types, homogeneous or pneumonic infiltrates and nodules, occurred later. Modern chemotherapy was very effective in the treatment of pulmonary Hodgkin9s disease. Since two-thirds of the patients who developed lung involvement already had stage IIIB or IV disease, the early use of chemotherapy should reduce the incidence of this common complication.
Mechanisms of Glomerular Immune Injury
Authors: Sriram S. Narsipur, Orjan W. Peterson, Robert Smith, Timothy D. Bigby, Sampath Parthasarathy, Francis B. Gabbai, Curtis B. Wilson, Roland C. Blantz
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Significant glomerular vasoconstriction and production of reactive oxygen species has been known to occur with exposure to anti–glomerular basement membrane antibody (AGBM-Ab) in the rat model. Previously published studies have demonstrated that such effects can be reduced by therapy with phentolamine, an α-adrenergic antagonist. It was hypothesized that antioxidant pretreatment with water-soluble probucol would improve glomerular hemodynamics 60 to 90 min after the administration of AGBM-Ab. These relationships were examined with both in vivo renal micropuncture and in vitro studies in rats. Single-nephron GFR (SNGFR) decreased markedly in untreated rats after AGBM-Ab as a result of afferent and efferent arteriolar vasoconstriction with consequent reductions in nephron plasma flow (SNPF) and decreases in the glomerular ultrafiltration coefficient (LpA). Basal SNGFR was increased, and SNGFR was significantly higher after AGBM-Ab in probucol-treated versus untreated rats. This finding was due solely to higher values for SNPF and prevention of afferent arteriolar constriction. A reduction in LpA after AGBM-Ab was not prevented by probucol treatment. In vitro analyses of glomeruli revealed reduced myeloperoxidase activity in antioxidant-treated rats. Lipoxygenase activity and leukotriene products, however, were not changed by antioxidant therapy, yet vasoconstriction was prevented. H2O2 generation before and after formyl-methionyl-leucyl-phenylalanine stimulation was significantly reduced before and after AGBM-Ab in glomeruli harvested from rats that were treated with the antioxidant. Antioxidant therapy in this model of AGBM-Ab injury did not prevent reductions in LpA, an index of glomerular membrane damage, but did prevent afferent arteriolar vasoconstriction. Reactive oxygen species generation was reduced by probucol. The specific mechanisms whereby antioxidant therapy ameliorates glomerular hemodynamic effects will be defined in additional studies and is likely to involve either enhanced vasodilator or diminished vasoconstrictor activity. E-mail [email protected]
Molecular Responses in Patients with Chronic Myelogenous Leukemia in Chronic Phase Treated with Imatinib Mesylate
Authors: Jorge Cortes, Moshe Talpaz, Susan O'Brien, Dan Jones, Rajyalakshmi Luthra, Jenny Shan, Francis Giles, Stefan Faderl, Srdan Verstovsek, Guillermo Garcia-Manero, Mary B. Rios, Hagop Kantarjian
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine the clinical significance of molecular response and relapse among patients with chronic myelogenous leukemia (CML) treated with imatinib. Experimental Design: We analyzed the results of quantitative PCR in 280 patients with CML in chronic phase who achieved complete cytogenetic remission with imatinib (117 after IFN-α failure and 163 previously untreated). Median follow-up was 31 months (range, 3-52 months). Results: Median BCR-ABL/ABL ratio before the start of therapy was 39.44 (range, 0.252-170.53). A major molecular response (BCR-ABL/ABL ratio &amp;lt;0.05%) was achieved in 174 (62%), and transcripts became undetectable (complete molecular response) in 95 (34%). By multivariate analysis, only treatment with high-dose imatinib (P = 0.02) was associated with achievement of a major molecular response. Nine of 166 (5%) patients who achieved a major molecular response lost their cytogenetic remission, compared with 25 of 68 (37%) among those who did not achieve this response (P &amp;lt; 0.0001). Patients achieving a major molecular response 12 months after the start of therapy had significantly better complete cytogenetic remission duration than others. A &amp;gt;1-log reduction in transcript levels after 3 months of therapy predicted for an improved probability of achieving a major molecular response at 24 months. Increasing levels of BCR-ABL transcripts predicted for a loss of cytogenetic remission only among patients who did not achieve a major molecular response. Conclusions: Achieving a major molecular response, particularly within the first year of therapy, is predictive of a durable cytogenetic remission and may be the future goal of therapy in CML.
Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants
Authors: Ralf J.P. van der Valk, Liesbeth Duijts, Nicolas J. Timpson, Muhammad T. Salam, Marie Standl, John A. Curtin, Jon Genuneit, Marjan Kerhof, Eskil Kreiner-Møller, Alejandro Cáceres, Anna Gref, Liming L. Liang, H. Rob Taal, Emmanuelle Bouzigon, Florence Demenais, Rachel Nadif, Carole Ober, Emma E. Thompson, Karol Estrada, Albert Hofman, André G. Uitterlinden, Cornélia van Duijn, Fernando Rivadeneira, Xia Li, Sandrah P. Eckel, Kiros Berhane, W. James Gauderman, Raquel Granell, David M. Evans, Beate St Pourcain, Wendy McArdle, John P. Kemp, George Davey Smith, Carla M.T. Tiesler, Claudia Flexeder, Angela Simpson, Clare S. Murray, Oliver Fuchs, Dirkje S. Postma, Klaus Bønnelykke, Maties Torrent, Martin Andersson, Patrick Sleiman, Hakon Hakonarson, William O. Cookson, Miriam F. Moffatt, Lavinia Paternoster, Erik Melén, Jordi Sunyer, Hans Bisgaard, Gerard H. Koppelman, Markus Ege, Adnan Custovic, Joachim Heinrich, Frank D. Gilliland, Alexander J. Henderson, Vincent W.V. Jaddoe, Johan C. de Jongste
Journal: Journal of Allergy and Clinical Immunology (2013)
Internships and Internships
Authors: G. Halsey Hunt
Journal: JAMA (1972)

In recent years we have become used to having what appear to be major differences of opinion dismissed as "a matter of semantics," since it frequently happens that two persons who appear to be in disagreement turn out on further analysis to be using different words to mean the same thing. Semantic confusion is caused by the use of words that may have different meanings to different people in different contexts. This problem may be more acute with words that have been rather recently adopted into English from other languages. The words "intern" and "internship" are examples of the problem which is familiar to those involved with graduates of medical schools outside the United States and Canada. The common acceptance of the internship as a normal part of the education of a physician in the United States, which began early in the 20th century, and the definition of the "Essentials
Secondary Heavy Chain Rearrangement
Authors: Debora R. Sekiguchi, Robert A. Eisenberg, Martin Weigert
Journal: The Journal of Experimental Medicine (2003)

The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles systemic lupus erythematosus (SLE). It is induced in nonautoimmune mice by the transfer of alloreactive T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies in this model. We induced cGVH in two anti-DNA H chain site-directed transgenic mouse strains. This resulted in clonal expansion and selection of specific mutations in the anti–double-stranded (ds) DNA B cell population. These data, together with a high frequency of anti-dsDNA B cell clones recovered as hybridomas, suggested that anti-dsDNAs are the product of an antigen-driven immune response. Genetic analysis associated this response with the generation of anti-dsDNA B cells through secondary rearrangements that replaced the site-directed transgene (sd-tg) with endogenous VH genes.
Carotid sinus baroreceptor reflex control and epinephrine. Influence on capacitive and resistive properties of the total pulmonary vascular bed of the dog.
Authors: A A Shoukas
Journal: Circulation Research (1982)

To quantify the importance of the carotid sinus baroreceptor reflex and the interaction with epinephrine infusion on total pulmonary vascular capacity and resistance, I have simultaneously measured total pulmonary vascular compliance, changes in pulmonary blood volumes, and changes in resistances in seven sodium pentobarbital-anesthetized dogs. A preparation was used that bypasses the right and left hearts allowing for the simultaneous measurement of the pulmonary as well as the systemic vascular bed parameters. At intrasinus pressures of 50, 125, and 200 mm Hg, without epinephrine infusion, the pulmonary vascular resistance was 0.134, 0.121, and 0.109 mm Hg/(ml per min per kg) and the systemic vascular resistance was 1.21, 0.87, and 0.63 mm Hg/(ml per min per kg). Epinephrine infusion of 1 microgram/min per kg at each intrasinus pressure caused the resistances of both vascular beds to increase. Pulmonary vascular resistance increased to 0.157 mm Hg/(ml per min per kg) and showed no further changes with changes in ISP. However, systemic vascular resistance did decrease from 1.49 to 1.41 and 1.25 at intrasinus pressures of 50, 125, and 200 mm Hg. During control runs, pulmonary vascular capacity changed 1.06 ml/kg and systemic capacity changed 7.63 ml/kg for SP changes between 50 and 200 mm Hg. Both responses were greatly attenuated after epinephrine infusion and amounted to only 0.17 ml/kg for the pulmonary and vascular bed and 2.26 ml/kg for the systemic vascular bed. The differences in capacity changes between control and epinephrine runs for the two vascular beds were nearly equal to the change in capacities brought about by epinephrine when it was infused at a fixed intrasinus pressure of 125 mm Hg. The pulmonary vascular compliance during the control runs increased from 0.303 to 0.329 ml/mm Hg per kg when ISP was increased from 50 to 200 mm Hg. After epinephrine infusion, the pulmonary compliance was 0.273 ml/mm Hg per kg and showed no changes with intrasinus pressure. Similar results were obtained for the systemic vascular compliance which was 2.07 ml/mm Hg per kg at an ISP of 50 mm Hg and increased to 2.39 ml/mm Hg per kg to an ISP of 200 mm Hg during control runs. After epinephrine infusion, the systemic compliance was 1.89 ml/mm Hg per kg and again showed no changes with ISP. These data indicate that the baroreceptor reflex can exert control of pulmonary and systemic vascular resistance and capacitance and epinephrine can greatly attenuate the reflex control of both vascular beds.
Treatment Outcomes of Patients with HIV and Tuberculosis
Authors: Payam Nahid, Leah C. Gonzalez, Irina Rudoy, Bouke C. de Jong, Alon Unger, L. Masae Kawamura, Dennis H. Osmond, Philip C. Hopewell, Charles L. Daley
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: The optimal length of tuberculosis treatment in patients coinfected with HIV is unknown.Objectives: To evaluate treatment outcomes for HIV-infected patients stratified by duration of rifamycin-based tuberculosis therapy.Methods: We retrospectively reviewed data on all patients with tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990 through 2001. Patients were followed for up to 12 months after treatment completion.Measurements and Main Results: Of 700 patients, 264 (38%) were HIV infected, 315 (45%) were not infected, and 121 (17%) were not tested. Mean duration of treatment was extended to 10.2 months for HIV-infected patients versus 8.4 months for uninfected/unknown patients (p < 0.001). Seventeen percent of the HIV-infected and 37% of the HIV uninfected/unknown patients received 6 months of rifamycin-based therapy. The relapse rate among HIV-infected was 9.3 per 100 person-years versus 1.0 in HIV-uninfected/unknown patients (p < 0.001). HIV-infected individuals who received a standard 6-month rifamycin-based regimen were more likely to relapse than those treated longer (adjusted hazard ratio, 4.33; p = 0.02). HIV-infected individuals who received intermittent therapy were also more likely to relapse than those treated on daily basis (adjusted hazard ratio, 4.12; p = 0.04). The use of highly active antiretroviral therapy was associated with more rapid conversion of smears and cultures and with improved survival.Conclusions: HIV-infected patients who received a 6-month rifamycin-based course of tuberculosis treatment or who received intermittent therapy had a higher relapse rate than HIV-infected subjects who received longer therapy or daily therapy, respectively. Standard 6-month therapy may be insufficient to prevent relapse in patients with HIV.
A Dutch patient presenting with a rare clinical syndrome
Authors: G. Elshout, F. J. M. F. Dor, L. C. Verhoog, L. Berk, W. W. Vrijland
Journal: Gut (2010)

A 67-year-old Caucasian male presented with persistent diarrhoea, weight loss of 15 kg in 3 months, and onychodystrophy. Family history is negative for colon carcinoma. He worked in oil trading and had extensive exposure to sulfuric acid, ammonia and gum resin. Physical examination revealed a vaguely palpable mass and tenderness in the left lower abdominal quadrant. Onycholysis of the fingernails (figure 1) and toenails, alopecia (figure 2) and hyperpigmentation of the skin were noted. CT demonstrated two circular thickenings in the sigmoid and colon ascendens. A …
Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome
Authors: David Kavanagh, Elizabeth J. Kemp, Elizabeth Mayland, Robin J. Winney, Jeremy S. Duffield, Graham Warwick, Anna Richards, Roy Ward, Judith A Goodship, Timothy H.J. Goodship
Journal: Journal of the American Society of Nephrology (2005)

Mutations in the plasma complement regulator factor H (CFH) and the transmembrane complement regulator membrane co-factor protein (MCP) have been shown to predispose to atypical hemolytic uremic syndrome (HUS). Both of these proteins act as co-factors for complement factor I (IF). IF is a highly specific serine protease that cleaves the alpha-chains of C3b and C4b and thus downregulates activation of both the classical and the alternative complement pathways. This study looked for IF mutations in a panel of 76 patients with HUS. Mutations were detected in two patients, both of whom had reduced serum IF levels. A heterozygous bp change, c.463 G>A, which results in a premature stop codon (W127X), was found in one, and in the other, a heterozygous single base pair deletion in exon 7 (del 922C) was detected. Both patients had a history of recurrent HUS after transplantation. This is in accordance with the high rate of recurrence in patients with CFH mutations. Patients who are reported to have mutations in MCP, by contrast, do not have recurrence after transplantation. As with CFH- and MCP-associated HUS, there was incomplete penetrance in the family of one of the affected individuals. This study provides further evidence that atypical HUS is a disease of complement dysregulation.
Suppression of macrophage oxidative metabolism by products of malignant and nonmalignant cells.
Authors: A Szuro-Sudol, C F Nathan
Journal: The Journal of Experimental Medicine (1982)

Each of 11 tumors tested produced a factor that markedly suppressed the ability of macrophages to release H2O2 or O.2- in response to phorbol myristate acetate or zymosan. Four of seven normal cell types produced a similar activity, which was 3.5-7 times lower in titer than that in tumor cell-conditioned medium (TCM), and which was much more rapidly reversible in its effects. TCM caused 50% inhibition of H2O2 release when it was present in the medium for 48 h at a concentration of 13%, or when 100% TCM was present in the medium for 18 h. The H2O2-releasing capacity of macrophages incubated in TCM only returned to control levels by 6 d after its removal. TCM prevented augmentation of H2O2-releasing capacity by lymphokines. The titer of suppressive activity in TCM depended on both the concentration of tumor cells and the duration of their incubation. TCM did not augment the activity of catalase, myeloperoxidase, glutathione peroxidase, or glutathione reductase or the content of glutathione within macrophages, suggesting that decreased synthesis rather than increased catabolism was responsible for reduced secretion of H2O2. Suppression of the release of H2O2 or O.2- by TCM appeared to be a relatively specific effect, in that TCM increased macrophage spreading and adherence to glass while exerting little influence on rates of phagocytosis, synthesis of protein, or secretion of lysozyme, plasminogen activator, or arachidonic acid and its metabolites. Thus, tumor cells and some normal cells can secrete a factor that selectively deactivates macrophage oxidative metabolism.