tbuckley/cabot-search huggingface dataset:
Further Observations on the Inhibition of Tumor Growth by &lt;italic&gt;Corynebacterium parvum&lt;/italic&gt; With Cyclophosphamide. X. Effect of Treatment on Tumor Cell Kinetics in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bernard Fisher, Nurten Gunduz
Journal: JNCI Journal of the National Cancer Institute (1979)

With the use of female C3HeB/Fe mice, studies were done to ascertain whether the inhibition of tumor growth observed following administration of cyclophosphamide (CY) and Corynebacterlum parvum, which was greater than that resulting from the use of either agent alone, could be related to the effect of such combined chemoimmunotherapy on the cytokinetics of treated tumors. Growth characteristics and cytokinetics of untreated C3H mammary tumors were determined so that alterations resulting from therapy could be evaluated. C3H mammary tumors displayed gompertzian growth; labeling Index and growth fraction decreased, whereas cell-cycle time and DNA synthesis time Increased with tumor age and volume. A depression of the labeling index and growth fraction and an increase in DNA synthesis time occurred following a single dose of CY. The effect was maximum at approximately 5 days, with evidence of recovery by 7 days. Repeated doses of CY produced a similar cyclic effect that was less pronounced with successive doses. A single dose of C. parvum alone resulted in changes similar to those observed with CY. However, they occurred more, promptly (maximum at 1 day) and were of lesser magnitude and shorter duration. The use of C. parvum and CY therapy prolonged the kinetic changes caused by CY. The effect of the chemoimmunotherapy Interval was evaluated, and a chemoimmunotherapy interval of +4 days produced greater kinetic alterations than did a chemoimmunotherapy interval of −3 or zero days. That interval (+4 days) has been most effective in inhibiting tumor growth. Multiple courses of combination therapy resulted in a reduction in labeling index and growth fraction and an increase in DNA synthesis time greater than those produced by CY alone. These results were in keeping with findings relative to tumor growth. The findings indicate that the immunopotentlator C. parvum affects tumor cell kinetics and that the greater inhibition of tumor growth resulting after chemoimmunotherapy is reflected in the cytokinetic changes occurring during such treatment.
Targeting the TLR Co-Receptor CD14 with TLR2-Derived Peptides Modulates Immune Responses to Pathogens
Authors: Anne-Catherine Raby, Benjamin Holst, Emmanuel Le Bouder, Constantino Diaz, Edgardo Ferran, Laurence Conraux, Jean-Claude Guillemot, Barbara Coles, Ann Kift-Morgan, Chantal S. Colmont, Tamas Szakmany, Pascual Ferrara, Judith E. Hall, Nicholas Topley, Mario O. Labéta
Journal: Science Translational Medicine (2013)

Toll-like receptor–mediated responses to pathogens can be modulated by targeting the TLR co-receptor CD14.
Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial
Authors: T. Ooi, R.StC. Barnetson, L. Zhuang, S. McKane, J.H. Lee, H.B. Slade, G.M. Halliday
Journal: British Journal of Dermatology (2005)

Imiquimod 5% cream is a topically applied immune response modifier that has been shown to give effective treatment of actinic keratosis (AK). The therapeutic effects of imiquimod are likely to involve the provocation of a cutaneous immune response against abnormal cells, an assumption based on a strong correlation between complete clearance rates and the severity of the local skin reactions (erythema, oedema, erosion/ulceration, weeping/exudation and scabbing/crusting); however, no clinical studies have conclusively proved this mechanism.To determine the nature of cellular infiltrates induced by the application of imiquimod to AK lesions and to study cells involved in the cutaneous immune response.Eighteen patients participated in this phase I, randomized, double-blind, parallel group, vehicle-controlled study. Enrolled patients were randomized in a 2 : 1 ratio to receive imiquimod cream or vehicle cream and applied study cream to five lesions on the scalp, forearm or upper trunk once daily, three days per week for up to 16 weeks. Each patient had punch biopsies of two distinct AK lesions: a lesion was biopsied before treatment to obtain baseline biomarker levels, and a different lesion was biopsied after 2 weeks of treatment. Biopsy specimens were examined using routine and immunohistochemical staining.The imiquimod group showed statistically significant increases from baseline to week 2 in tissue biomarker levels for CD3, CD4, CD8, CD11c, CD86/CD11c, CD68, HLA-DR and TUNEL. No significant differences were seen for the vehicle group. Complete clearance of all treated AK lesions was achieved in five of 11 (45%) imiquimod patients and in none of six vehicle patients.Imiquimod stimulates a cutaneous immune response characterized by increases in activated dendritic cells and CD4+ and CD8+ T cells.
Economic change, crime, and mortality crisis in Russia: regional analysis
Authors: P. Walberg, M. McKee, V. Shkolnikov, L. Chenet, D. A Leon
Journal: BMJ (1998)

<b>Objective</b>: To identify which aspects of socioeconomic change were associated with the steep decline in life expectancy in Russia between 1990&nbsp;and 1994.&nbsp; <b>Design</b>: Regression analysis of regional data, with percentage fall in male life expectancy as dependent variable and a range of socioeconomic measures reflecting transition, change in income, inequity, and social cohesion as independent variables. Determination of contribution of deaths from major causes and in each age group to changes in both male and female life expectancy at birth in regions with the smallest and largest declines. <b>Setting</b>: Regions (oblasts) of European Russia(excluding Siberia and those in the Caucasus affected by the Chechen war). <b>Subjects</b>: The population of European Russia. <b>Results</b>: The fall in life expectancy at birth varied widely between regions, with declines for men and women highly correlated. The regions with the largest falls were predominantly urban, with high rates of labour turnover, large increases in recorded crime, and a higher average but unequal distribution of household income. For both men and women increasing rates of death between the ages of 30&nbsp;and 60&nbsp;years accounted for most of the fall in life expectancy, with the greatest contributions being from conditions directly or indirectly associated with heavy alcohol consumption. <b>Conclusions</b>: The decline in life expectancy in Russia in the 1990s cannot be attributed simply to impoverishment. Instead, the impact of social and economic transition, exacerbated by a lack of social cohesion, seems to have played a major part. The evidence that alcohol is an important proximate cause of premature death in Russia is strengthened.
HIF1α in hypoxia
Authors: Kris McLaughlin
Journal: Thorax (2008)

Conjugation of small ubiquitin-related modifier proteins (SUMO) to form larger substrates has been implicated in the regulation of multiple cellular processes in mammals including transcription, cell signalling and cancer progression. This conjugation is a dynamic process that can be reversed by a family of Sentrin/SUMO-specific proteases (SENPs).

This study investigated the physiological consequences of SUMOylation and deSUMOylation …
Mitogenomic Diversity in Tatars from the Volga-Ural Region of Russia
Authors: B. Malyarchuk, M. Derenko, G. Denisova, O. Kravtsova
Journal: Molecular Biology and Evolution (2010)

To investigate diversity of mitochondrial gene pool of Tatars inhabiting the territory of the middle Volga River basin, 197 individuals from two populations representing Kazan Tatars and Mishars were subjected for analysis of mitochondrial DNA (mtDNA) control region variation. In addition, 73 mitochondrial genomes of individuals from Mishar population were sequenced completely. It was found that mitochondrial gene pool of the Volga Tatars consists of two parts, but western Eurasian component prevails considerably (84% on average) over eastern Asian one (16%). Eastern Asian mtDNAs detected in Tatars belonged to a heterogeneous set of haplogroups (A, C, D, G, M7, M10, N9a, Y, and Z), although only haplogroups A and D were revealed simultaneously in both populations. Complete mtDNA variation study revealed that the age of western Eurasian haplogroups (such as U4, HV0a, and H) is less than 18,000 years, thus suggesting re-expansion of eastern Europeans soon after the Last Glacial Maximum.
Lack of interleukin-1α or interleukin-1β inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice
Authors: Yehuda Kamari, Aviv Shaish, Einav Vax, Shay Shemesh, Michal Kandel-Kfir, Yaron Arbel, Sarita Olteanu, Iris Barshack, Shahar Dotan, Elana Voronov, Charles A. Dinarello, Ron N. Apte, Dror Harats
Journal: Journal of Hepatology (2011)
Randomized Study of Autologous Cytokine-Induced Killer Cell Immunotherapy in Metastatic Renal Carcinoma
Authors: Liang Liu, Weihong Zhang, Xiuying Qi, Hui Li, Jinpu Yu, Sheng Wei, Xishan Hao, Xiubao Ren
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The therapeutic benefit of the cytokine-induced killer (CIK) cells was unknown in the renal cell carcinoma (RCC). This prospectively randomized study was conducted to evaluate the effects of autologous CIK cell immunotherapy in patients with metastatic clear cell RCCs. Experimental Design: From June 2005 to June 2008, 148 patients with metastatic clear cell RCC were randomized to autologous CIK cell immunotherapy (arm 1, n = 74), or interleukin-2 treatment combination with IFN-α-2a (arm 2, n = 74). The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS) evaluated by Kaplan–Meier analyses and treatment HRs with the Cox proportional hazards model. Results: The 3-year PFS and OS in arm 1 were 18% and 61%, as compared with 12% and 23% in arm 2 (P = 0.031 and &amp;lt;0.001, respectively). The median PFS and OS in arm 1 were significantly longer than those in arm 2 (PFS, 12 vs. 8 months, P = 0.024; OS, 46 vs. 19 months, P &amp;lt; 0.001). Multivariate analyses indicated that the cycle count of CIK cell immunotherapy as a continuous variable was significantly associated with prolonged PFS [HR = 0.88; 95% confidence interval (CI), 0.84-0.93; P &amp;lt; 0.001] and OS (HR = 0.58; 95% CI, 0.48–0.69; P &amp;lt; 0.001) in arm 1. Conclusion: The data suggested that CIK cell immunotherapy could improve the prognosis of metastatic clear cell RCC, and increased cycle count of CIK cell treatment could further enhance the beneficial effects. Clin Cancer Res; 18(6); 1751–9. ©2012 AACR.
DEVELOPMENTAL AND SEXUAL FACTORS IN WOMEN: A COMPARISON BETWEEN CONTROL, NEUROTIC AND PSYCHOTIC GROUPS
Authors: GEORGE WINOKUR, SAMUEL B. GUZE, ERIC PFEIFFER
Journal: American Journal of Psychiatry (1959)

Comparison of groups of controls, neurotics, and psychotics were made by means of a structured interview. Developmental symptoms (enuresis and somnambulism) were not noted to be harbingers of psychiatric disease. Menopausal symptoms, dysmenorrhea, dyspareunia, frequency of orgasms and enjoyment of coitus did not differentiate the groups. A higher incidence of miscarriages was noted in psychotic patients and a lower incidence of somnambulism was seen in the psychoses. A significantly higher percent of psychotics had intercourse infrequently, although in other sexual areas as noted above the psychotic group was like the others.
Wiskott-Aldrich syndrome protein–mediated actin dynamics control type-I interferon production in plasmacytoid dendritic cells
Authors: Francesca Prete, Marco Catucci, Mayrel Labrada, Stefania Gobessi, Maria Carmina Castiello, Elisa Bonomi, Alessandro Aiuti, William Vermi, Caterina Cancrini, Ayse Metin, Sophie Hambleton, Robbert Bredius, Luigi Daniele Notarangelo, Mirjam van der Burg, Ulrich Kalinke, Anna Villa, Federica Benvenuti
Journal: The Journal of Experimental Medicine (2013)

Mutations in Wiskott-Aldrich syndrome (WAS) protein (WASp), a regulator of actin dynamics in hematopoietic cells, cause WAS, an X-linked primary immunodeficiency characterized by recurrent infections and a marked predisposition to develop autoimmune disorders. The mechanisms that link actin alterations to the autoimmune phenotype are still poorly understood. We show that chronic activation of plasmacytoid dendritic cells (pDCs) and elevated type-I interferon (IFN) levels play a role in WAS autoimmunity. WAS patients display increased expression of type-I IFN genes and their inducible targets, alteration in pDCs numbers, and hyperresponsiveness to TLR9. Importantly, ablating IFN-I signaling in WASp null mice rescued chronic activation of conventional DCs, splenomegaly, and colitis. Using WASp-deficient mice, we demonstrated that WASp null pDCs are intrinsically more responsive to multimeric agonist of TLR9 and constitutively secrete type-I IFN but become progressively tolerant to further stimulation. By acute silencing of WASp and actin inhibitors, we show that WASp-mediated actin polymerization controls intracellular trafficking and compartmentalization of TLR9 ligands in pDCs restraining exaggerated activation of the TLR9–IFN-α pathway. Together, these data highlight the role of actin dynamics in pDC innate functions and imply the pDC–IFN-α axis as a player in the onset of autoimmune phenomena in WAS disease.
The risk of surgery in patients with liver disease
Authors: Lawrence S. Friedman
Journal: Hepatology (1999)

Because of the multiple functions of the liver-synthesis of most serum proteins, metabolism of nutrients and drugs, excretion and detoxification of endogenous toxins and exogenous agents, and filtering of portal venous blood-assessing the risk of surgery in patients with liver disease is a challenging endeavor.Any or all of the functions of the liver may be impaired in patients with liver disease. 1,2As a result, the pharmacokinetic parameters of anesthetics, muscle relaxants, analgesics, and sedatives can be affected by changes in binding to plasma proteins, detoxification, and excretion; bleeding risk can be increased because of coagulopathy; and susceptibility to infection can be increased because of altered functioning of hepatic reticuloendothelial cells and other changes in the immune system as well as portal hypertension.Perhaps most importantly, a diseased liver is particularly susceptible to the hemodynamic changes that accompany surgery.On the other hand, operative risk is probably not increased in the vast majority of patients with liver disease, including most of those with chronic hepatitis C, in whom liver function is preserved.Mild elevations of serum aminotransferase, alkaline phosphatase, or bilirubin levels are frequent after surgical procedures, whether performed under general, spinal, or epidural anesthesia. 3,4In patients without preexisting liver disease, these perturbations are usually transient, of no clinical significance, and often unnoticed.Clinically important hepatic dysfunction is more likely to occur in patients with preexisting liver disease.This review will consider the factors that contribute to perioperative hepatic dysfunction and prediction of operative risk in patients with liver disease undergoing surgery other than liver transplantation.
Very Low Density Lipoprotein
Authors: Tova Chajek, Shlomo Eisenberg
Journal: Journal of Clinical Investigation (1978)

The fate of rat plasma very low density lipoprotein (VLDL) constituents was determined in the isolated perfused rat heart. VLDL was labeled with [(14)C]palmitate, (32)P-phospholipids, [(3)H] cholesterol, and (125)I-apolipoprotein C (apoC). Perfusions were performed with an albumin-containing buffer and without plasma. Radioactivity was followed in fractions of d < 1.019, d 1.019-1.04, d 1.04-1.21, and d > 1.21 g/ml, prepared by ultracentrifugation.VLDL triglycerides were progressively hydrolyzed to fatty acids (10-120-min perfusions). Concomitantly, phospholipids, cholesterol (predominantly unesterified), and apoC were removed from the VLDL to all other fractions. About 30-35% of the phosphatidylcholine was hydrolized to lysophosphatidylcholine and was recovered at d > 1.21 g/ml. The phosphatidylcholine-and triglyceride-hydrolyzing activities were confined to membrane supported enzyme(s). The other 60-65% of the phosphatidylcholine was removed unhydrolyzed and was found in fractions of d 1.019-1.04 (10-15%), d 1.04-1.21 (25-30%), and d > 1.21 g/ml (15-20%). [(32)P]Sphingomyelin accumulated at the fraction of d 1.04-1.21 g/ml. Unesterified cholesterol was found in the fraction of d 1.04-1.21 g/ml. ApoC was recovered predominantly in fractions of d 1.04-1.21 (50-60%) and d > 1.21 g/ml (30-40%). Cholesteryl esters were associated with VLDL during the hydrolysis of 50-70% of the triglycerides, but with advanced lipolysis, appeared in higher densities, mainly d 1.019-1.04 g/ml. The fraction of d 1.04-1.21 g/ml, (containing phosphatidylcholine, sphingomyelin, unesterified cholesterol, and apoC) contained by negative staining, many disk-like structures. The study demonstrated that removal of surface constituents (phospholipids, unesterified cholesterol, and apoC) during lipolysis of VLDL is an intrinsic feature of the lipolytic process, and is independent of the presence of plasma. It also indicated that surface constituents may be removed in a particulated form.
ONSET AND DURATION OF DNA SYNTHESIS IN ANTIBODY-FORMING CELLS AFTER ANTIGEN
Authors: Edward P. Cohen, David W. Talmage
Journal: The Journal of Experimental Medicine (1965)

Within 5 hours after the intravenous injection of particulate antigen into the primarily immunized mouse, precursors of antibody-forming cells began DNA synthesis as shown by the incorporation of tritium-labeled thymidine. DNA synthesis continued for at least 24 hours and essentially stopped by 48 hours. No DNA synthesis in antibody-forming precursor cells occurred before the injection of antigen.
Dual wavelength (532 and 633 nm) laser Doppler imaging of plaque psoriasis
Authors: A.K. Murray, A.L. Herrick, T.L. Moore, T.A. King, C.E.M. Griffiths
Journal: British Journal of Dermatology (2005)

Journal Article Dual wavelength (532 and 633 nm) laser Doppler imaging of plaque psoriasis A.K. Murray, A.K. Murray Laser Photonics Group, Department of Physics and Astronomy, University of Manchester, Oxford Road, Manchester M13 9PL, U.KRheumatic Diseases Centre A.K. Murray. E‐mail: andrea.murray@manchester.ac.uk Search for other works by this author on: Oxford Academic Google Scholar A.L. Herrick, A.L. Herrick Rheumatic Diseases Centre Search for other works by this author on: Oxford Academic Google Scholar T.L. Moore, T.L. Moore Rheumatic Diseases Centre Search for other works by this author on: Oxford Academic Google Scholar T.A. King, T.A. King Laser Photonics Group, Department of Physics and Astronomy, University of Manchester, Oxford Road, Manchester M13 9PL, U.K Search for other works by this author on: Oxford Academic Google Scholar C.E.M. Griffiths C.E.M. Griffiths Dermatology Centre, Hope Hospital, Salford, Manchester M6 8HD, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 6, 1 June 2005, Pages 1182–1186, https://doi.org/10.1111/j.1365-2133.2005.06479.x Published: 01 June 2005 Article history Accepted: 22 September 2004 Published: 01 June 2005
MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes
Authors: Xiaoqi Zheng, Qian Zhao, Hua-Jun Wu, Wei Li, Haiyun Wang, Clifford A Meyer, Qian Alvin Qin, Han Xu, Chongzhi Zang, Peng Jiang, Fuqiang Li, Yong Hou, Jianxing He, Jun Wang, Jun Wang, Peng Zhang, Yong Zhang, Xiaole Shirley Liu
Journal: Genome biology (2014)

Abstract We propose a statistical algorithm MethylPurify that uses regions with bisulfite reads showing discordant methylation levels to infer tumor purity from tumor samples alone. MethylPurify can identify differentially methylated regions (DMRs) from individual tumor methylome samples, without genomic variation information or prior knowledge from other datasets. In simulations with mixed bisulfite reads from cancer and normal cell lines, MethylPurify correctly inferred tumor purity and identified over 96% of the DMRs. From patient data, MethylPurify gave satisfactory DMR calls from tumor methylome samples alone, and revealed potential missed DMRs by tumor to normal comparison due to tumor heterogeneity.
Roles of the Akt/GSK-3 and Wnt Signaling Pathways in Schizophrenia and Antipsychotic Drug Action
Authors: Zachary Freyberg, Stephen J. Ferrando, Jonathan A. Javitch
Journal: American Journal of Psychiatry (2009)

Dopamine D2 receptor antagonism is a unifying property of all antipsychotic drugs in clinical use. Remarkably, the effector molecules through which these medications exert their actions remain poorly characterized. Increasing attention is being focused on Akt/glycogen synthase kinase-3 (GSK-3) and wingless (Wnt) signaling pathways, which have been associated with schizophrenia in a number of genetic and postmortem studies. Antipsychotic medications may treat symptoms of psychosis, at least in part, through modulation of levels and activity of Akt, GSK-3, and Wnt-related intracellular signaling. The authors review evidence that Akt/GSK-3 and Wnt-related pathways are involved in the pathogenesis of schizophrenia as well as details of intracellular events related to these molecules mediated by both typical and atypical antipsychotic medications. Further study of Akt/GSK-3 and Wnt signaling may ultimately lead to alternative therapeutics of schizophrenia-related disorders.
The Olympic Book of Sports Medicine
Authors: Henry E. Robson
Journal: British Journal of Sports Medicine (1988)

be recommended for individuals who were judged to be in a 'high-risk' category.Finally, although our subjects were requested to produce selected levels of effort on only three consecutive occasions, there was a strong trend towards improved correspondence of RPE and both heart rate and V02 at the lower levels of RPE.This suggests that practice is required if RPE is to be employed with confidence as a prescriptive device where most judgements are likely to be made in the intermediate effort levels of the scale.
Age, Race, Diabetes, Blood Pressure, and Mortality among Hemodialysis Patients
Authors: Orrin B. Myers, Christopher Adams, Mark R. Rohrscheib, Karen S. Servilla, Dana Miskulin, Edward J. Bedrick, Philip G. Zager
Journal: Journal of the American Society of Nephrology (2010)

Observational studies involving hemodialysis patients suggest a U-shaped relationship between BP and mortality, but the majority of these studies followed large, heterogeneous cohorts. To examine whether age, race, and diabetes status affect the association between systolic BP (SBP; predialysis) and mortality, we studied a cohort of 16,283 incident hemodialysis patients. We constructed a series of multivariate proportional hazards models, adding age and BP to the analyses as cubic polynomial splines to model potential nonlinear relationships with mortality. Overall, low SBP associated with increased mortality, and the association was more pronounced among older patients and those with diabetes. Higher SBP associated with increased mortality among younger patients, regardless of race or diabetes status. We observed a survival advantage for black patients primarily among older patients. Diabetes associated with increased mortality mainly among older patients with low BP. In conclusion, the design of randomized clinical trials to identify optimal BP targets for patients with ESRD should take age and diabetes status into consideration.