tbuckley/cabot-search huggingface dataset:
The effect of zinc on alkaline phosphatase activity in rheumatoid synovial tissue.
Authors: J J Johnstone, L Bitensky, B Cashman, J Chayen
Journal: Annals of the Rheumatic Diseases (1978)

To examine the reported beneficial effect of zinc in rheumatoid arthritis, rheumatoid synovial tissue has been maintained in vitro in non-proliferative culture with or without zinc sulphate in the culture medium. Alkaline phosphatase activity was measured by microdensitometry of the cytochemical reaction in cryostat sections; the activity in blood vessels was measured separately from that in the supporting tissue below the synovial surface. Zinc enhanced this activity optimally at concentrations of between 10(-5) and 10(-4) mol/l.
Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial
Authors: Maryline Bonnet, Nilesh Bhatt, Elisabeth Baudin, Carlota Silva, Christophe Michon, Anne-Marie Taburet, Laura Ciaffi, Agnès Sobry, Rui Bastos, Elizabete Nunes, Christine Rouzioux, Ilesh Jani, Alexandra Calmy
Journal: The Lancet Infectious Diseases (2013)
Topical aminolaevulinic acid- and aminolaevulinic acid methyl ester-based photodynamic therapy with red and violet light: influence of wavelength on pain and erythema
Authors: P. Mikolajewska, V. Iani, A. Juzeniene, J. Moan
Journal: British Journal of Dermatology (2009)

Photodynamic therapy (PDT) is based on the combination of an exogenously administered precursor of photosensitizer [protoporphyrin IX (PpIX)] synthesis and exposure to light. Choosing the optimal wavelength is important. Red light penetrates deeper into tissue, while violet light is more efficient in activating PpIX but does not penetrate so deeply.We studied PpIX formation and the PDT effect after application to human skin of creams containing aminolaevulinic acid (ALA) and aminolaevulinic acid methyl ester (MAL). The aim of the study was to investigate whether the wavelength of the light used has an influence on pain sensations during topical PDT with the different prodrugs.ALA cream (10%) and MAL cream (10%) were topically applied on the skin of 10 healthy volunteers. After 24 h the application site was exposed to 8 mW cm(-2) violet laser or to 100 mW cm(-2) red laser light. The erythema index was monitored up to 24 h after light exposure. For the first time the pain during topical ALA- and MAL-PDT was assessed by measuring the time taken for pain to occur. Also, for the first time, the intensities of the light sources were calibrated so as to have the same relative quantum efficiency. Results The pain sensation during ALA-PDT with red light came 22 s sooner than during ALA-PDT with violet light, which is statistically significant (P < 0.05). Moreover, ALA-PDT with red light gave stronger and more persistent erythema than ALA-PDT with violet light. ALA induced about three times more PpIX than MAL. No statistically significant differences were found for erythema, or for the time for pain to occur, in the case of MAL-PDT with red vs. violet light.Topical ALA-PDT with violet light allows longer exposure times before pain is induced and gives less erythema as compared with topical ALA-PDT with red light.
Maintenance Therapy for Ovarian Cancer: Of Helsinki and Hippocrates
Authors: William Patrick McGuire
Journal: Journal of Clinical Oncology (2009)

In this issue of Journal of Clinical Oncology (JCO), an Italian consortium presents the results of a randomized, phase III trial 1 in ovarian cancer that addresses the potential value of continued therapy (ie, maintenance therapy) after attainment of a clinical or pathologic complete response to primary treatment.They conclude that six additional every-3-week cycles of paclitaxel monotherapy do not alter the important end points of progression-free or overall survival.Though there are some criticisms that can be leveled at the conduct of the trial, the negative results are not surprising in the context of the preponderance of data in ovarian cancer-as well as in other solid tumors-that fail to show convincingly that such a strategy is effective.One fault with this study is that 15% of patients in the control arm received some maintenance paclitaxel, 6% of the patients in the maintenance arm received no paclitaxel, and an additional 3% in the maintenance arm discontinued therapy early because of withdrawal of consent.However, in both the intent-to-treat analysis and the perprotocol analysis, no differences emerged in outcomes as a function of providing or withholding maintenance therapy.These data are in concert with multiple negative studies that have used the phase III, randomized trial design to test high-dose chemotherapy with stemcell rescue, intravenous topotecan, intravenous epirubicin, intravenous monoclonal antibody directed at CA-125 (ie, oregovomab), subcutaneous interferon alfa, intraperitoneal yttrium-90 -labeled monoclonal antibody directed against the MUC-1 antigen, intraperitoneal phosphorus-32 chromic phosphate, and whole-abdomen radiation therapy.In every instance, additional treatment has failed to alter progression or survival in patients who have no clinical evidence of disease after standard therapy with surgery and chemotherapy.These studies are referenced in the article by Pecorelli et al 1 in this issue of JCO for those readers unfamiliar with the specifics of each study.So why, you might wonder, is this editorial even being written?There remains a single randomized, phase III trial that came to the opposite conclusion from the study by Pecorelli et al 1 in this issue of JCO.That divergent study of 277 patients, published by the Southwest Oncology Group and Gynecologic Oncology Group (SWOG/GOG) in 2003, 2 found a statistically significant, 7-month difference in median progression-free survival (28 v 21 months) for either 12 or three additional cycles, respectively, of paclitaxel monotherapy in patients with advanced disease who had attained a clinical complete response with primary therapy.This difference led the Data Monitoring Committee to suspend the protocol and to eventually close the study when approximately half the proposed accrual had occurred.A survival advantage never emerged.Proponents of maintenance therapy have
Standardisation of the measurement of lung volumes
Authors: J. Wanger, J. L. Clausen, A. Coates, O. F. Pedersen, V. Brusasco, F. Burgos, R. Casaburi, R. Crapo, P. Enright, C. P. M. van der Grinten, P. Gustafsson, J. Hankinson, R. Jensen, D. Johnson, N. MacIntyre, R. McKay, M. R. Miller, D. Navajas, R. Pellegrino, G. Viegi
Journal: European Respiratory Journal (2005)
Quantitative studies on T cell diversity. III. Limiting dilution analysis of precursor cells for T helper cells reactive to xenogeneic erythrocytes.
Authors: I Melchers, K Fey, K Eichmann
Journal: The Journal of Experimental Medicine (1982)

Splenic T cells exposed to concanavalin A (Con A), and subsequently to factors produced by rat spleen cells in response to Con A (Con A sup), acquire the ability to function as helper T (TH) cells in response to xenogeneic erythrocytes (RBC). Help is measured as the reconstitution of the plaque-forming cell response of a spleen cell population depleted of T cells by treatment with anti-Thy-1 serum and complement. We propose that precursor TH cells differentiate during the in vitro treatment into mature TH cells. As differentiation occurs under limiting dilution conditions, an estimation of the precursor frequency should in principle be possible. However, a single-hit Poisson distribution does not fit our data. Instead, we observe, dependent on the T cell concentration, three separate "peaks" of response. In many experiments, using sheep, horse, and chicken RBC as antigens, we reproducibly find these "peaks" at 40-190, 600-3,000, and 20,000-100,000 T cells, placed into limiting dilution cultures, respectively. By various experiments we can show that the helper activity is not due to passively transferred rat factors, but to the titrated cells themselves. The active cell is a T cell that appears to function in an antigen-specific way and to require direct cell contact to do so. It thus resembles the classical helper T cell. As we find precursor TH cells already at very low concentrations of T cells, we titrated the range between 0 and 100 T cells/well carefully. The bent shape of the titration curves does not always allow a statistically satisfying regression analysis, and we therefore cannot estimate precise precursor frequencies from every experiment. However, a common sense argument can be made that these frequencies must be on the order of 1/10-1/100 T cells. We propose that the limiting dilution curves obtained in this system most likely reflect fundamentally important cellular interactions that regulate immunological effector functions. We favor a concept of independently interacting sets of helper and suppressor T cells of various frequencies, but other models are possible.
Low Gene Expression Conferred by Association of an Allele of the 5-HT<sub>2C</sub>Receptor Gene With Antipsychotic-Induced Weight Gain
Authors: Paul R. Buckland, Bastiaan Hoogendoorn, Carol A. Guy, S. Kaye Smith, Sharon L. Coleman, Michael C. O’Donovan
Journal: American Journal of Psychiatry (2005)

Association has been reported between the C allele of a -759C/T polymorphism in the promoter of the 5-HT2C receptor gene (HTR2C) and antipsychotic-induced weight gain, suggesting that polymorphic HTR2C expression influences this phenotype. The authors tested this polymorphism, and other promoter variants, for effects on HTR2C transcription.Six HTR2C promoter haplotypes constructed from four polymorphisms were cloned into a luciferase reporter gene plasmid. Their transcriptional activities were then compared in two human cell lines.All haplotypes containing the -759C allele showed less transcriptional activity than haplotypes containing the -759T allele. The A allele of a -997G/A polymorphism was also associated with reduced expression.These findings suggest that the -759C allele is functional and results in relative underexpression of HTR2C. Reduced expression of HTR2C mRNA may underlie vulnerability to weight gain following antipsychotic treatment.
Synovial membrane p53 protein immunoreactivity in rheumatoid arthritis patients
Authors: C S. Lee
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> To examine the expression of the p53 protein in synovial membrane of rheumatoid arthritis (RA) patients and to compare this with the expression in normal synovial tissues in subjects without RA. <h3>METHODS</h3> Immunohistological expression of the p53 protein was studied using a streptavidin-biotin-peroxidase method and the monoclonal antibody DO-7, an antibody directed against both wild and mutant forms of p53 protein, in synovial tissues of RA patients (n=10) and from subjects with no known joint disease (n=4). <h3>RESULTS</h3> p53 protein expression was present in a small percentage of synovial cells in the majority of the RA patients (n=8; 80%) and in half of the normal control cases with no inflammatory joint disease (n=2; 50%). No sample had more than 5% cells staining with intranuclear pattern. The difference in synovial p53 immunoreactivity between the RA patients and normal controls is not statistically significant (p= 0.64; χ<sup>2</sup> contingency test). <h3>CONCLUSIONS</h3> This study has shown that p53 protein is only weakly expressed in the rheumatoid synovial membrane, with a low percentage of p53 protein immunostaining cells present, with intranuclear staining. These results suggest this is wild type p53 protein rather than mutant protein. These findings suggest that synovial p53 protein expression may not be important in the pathogenesis of RA and may only represent a reactive repair process to DNA damage secondary to the immune and inflammatory reactions associated with the disease.
Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans
Authors: Kimber L. Stanhope, Jean Marc Schwarz, Nancy L. Keim, Steven C. Griffen, Andrew A. Bremer, James L. Graham, Bonnie Hatcher, Chad L. Cox, Artem Dyachenko, Wei Zhang, John P. McGahan, Anthony Seibert, Ronald M. Krauss, Sally Chiu, Ernst J. Schaefer, Masumi Ai, Seiko Otokozawa, Katsuyuki Nakajima, Takamitsu Nakano, Carine Beysen, Marc K. Hellerstein, Lars Berglund, Peter J. Havel
Journal: Journal of Clinical Investigation (2009)

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.
Genome-Wide Association Study for Coronary Artery Calcification With Follow-Up in Myocardial Infarction
Authors: Christopher J. O'Donnell, Maryam Kavousi, Albert V. Smith, Sharon L.R. Kardia, Mary F. Feitosa, Shih-Jen Hwang, Yan V. Sun, Michael A. Province, Thor Aspelund, Abbas Dehghan, Udo Hoffmann, Lawrence F. Bielak, Qunyuan Zhang, Gudny Eiriksdottir, Cornelia M. van Duijn, Caroline S. Fox, Mariza de Andrade, Aldi T. Kraja, Sigurdur Sigurdsson, Suzette E. Elias-Smale, Joanne M. Murabito, Lenore J. Launer, Aad van der Lugt, Sekar Kathiresan, Gabriel P. Krestin, David M. Herrington, Timothy D. Howard, Yongmei Liu, Wendy Post, Braxton D. Mitchell, Jeffrey R. O'Connell, Haiqing Shen, Alan R. Shuldiner, David Altshuler, Roberto Elosua, Veikko Salomaa, Stephen M. Schwartz, David S. Siscovick, Benjamin F. Voight, Joshua C. Bis, Nicole L. Glazer, Bruce M. Psaty, Eric Boerwinkle, Gerardo Heiss, Stefan Blankenberg, Tanja Zeller, Philipp S. Wild, Renate B. Schnabel, Arne Schillert, Andreas Ziegler, Thomas F. Münzel, Charles C. White, Jerome I. Rotter, Michael Nalls, Matthijs Oudkerk, Andrew D. Johnson, Anne B. Newman, Andre G. Uitterlinden, Joseph M. Massaro, Julie Cunningham, Tamara B. Harris, Albert Hofman, Patricia A. Peyser, Ingrid B. Borecki, L. Adrienne Cupples, Vilmundur Gudnason, Jacqueline C.M. Witteman
Journal: Circulation (2011)

Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI.
Differential requirements of B cells from normal and allergic subjects for the induction of IgE synthesis by an alloreactive T cell clone.
Authors: D T Umetsu, D Y Leung, R Siraganian, H H Jabara, R S Geha
Journal: The Journal of Experimental Medicine (1985)

Human T cell helper/inducer clones were used to induce IgE synthesis in B cells from both allergic and nonallergic donors. An alloreactive T cell clone, activated by recognition of specific HLA-DR antigens, stimulated peripheral blood B cells from both allergic and nonallergic donors to synthesize IgE antibody. B cells of allergic donors differed from those of nonallergic donors in their requirements for induction of IgE synthesis. Induction of IgE synthesis in B cells from nonallergic individuals occurred only under conditions of cognate interaction, in which the B cells expressed the alloantigen recognized by the T cells. In contrast, IgE synthesis in B cells from allergic donors occurred under conditions of cognate interaction with T cells as well as bystander conditions where the B cells did not express the alloantigen recognized by the T cell clones and where the T cell clones were stimulated by third-party monocytes bearing the relevant alloantigens. Furthermore, bystander stimulation of IgE synthesis in allergic donors occurred in the presence of tetanus toxoid (TT) antigen-specific T cell clones activated by the appropriate TT-pulsed monocytes. In contrast to the differing requirements of B cells from normal vs. allergic subjects for the induction of IgE synthesis, these B cells did not differ in their requirements for the induction of IgG synthesis. IgG synthesis was induced in all B cells under conditions of cognate interaction with the T cells as well as under conditions of bystander stimulation. These results suggest that cognate T-B cell interactions may be important in the development of IgE immune responses in the normal host.
Melanocyte detachment after skin friction in non lesional skin of patients with generalized vitiligo
Authors: Y. Gauthier, M. Cario-Andre, S. Lepreux, C. Pain, A. Taieb
Journal: British Journal of Dermatology (2003)

In vitiligo, melanocytes are gradually lost in depigmented macules of the skin. The disappearance of melanocytes has, however, not been clearly observed and consequently the aetiology of the disease (autoimmune, neural, cytotoxic) is still elusive. The starting point of vitiligo macules is frequently determined by local conditions such as wounds and excoriations, but may also follow minor traumas such as pressure or repeated friction. This prominent feature is often neglected.To clarify the biological consequences of repeated friction on the attachment and survival of melanocytes in non lesional vitiligo skin.Light reproducible skin friction was performed for 4 min on the volar forearm of 18 patients with extensive vitiligo and five controls with normal healthy skin. Biopsies from the test area and control skin were taken at 1, 4, 24 and 48 h following friction. Serial sections were examined with standard light microscopy, transmission electron microscopy, histochemistry and immunohistochemistry (dihydroxyphenylalanine, HMB-45, E-cadherin and an early apoptosis marker, M30 cytoDEATH antibody).The observation of sections at 1 and 48 h after friction on vitiligo skin and at all time points in controls revealed no changes. In contrast, in vitiligo skin at 4 and 24 h after friction, several melanocytes had undergone detachment and were found in various suprabasal positions, including the stratum spinosum, granular layer, and within and outside the stratum corneum.Detachment and transepidermal elimination of melanocytes following minor mechanical trauma in non lesional vitiligo skin is probably the cause of depigmentation occurring in the isomorphic response (Koebner phenomenon). We propose that transepidermal elimination of melanocytes in vitiligo should be regarded as a possible mechanism of chronic loss of pigment cells, perhaps previously damaged by another process.
Chemotherapy Response Score: Development and Validation of a System to Quantify Histopathologic Response to Neoadjuvant Chemotherapy in Tubo-Ovarian High-Grade Serous Carcinoma
Authors: Steffen Böhm, Asma Faruqi, Ian Said, Michelle Lockley, Elly Brockbank, Arjun Jeyarajah, Amanda Fitzpatrick, Darren Ennis, Thomas Dowe, Jennifer L. Santos, Linda S. Cook, Anna V. Tinker, Nhu D. Le, C. Blake Gilks, Naveena Singh
Journal: Journal of Clinical Oncology (2015)

Purpose To develop and validate a histopathologic scoring system for measuring response to neoadjuvant chemotherapy in interval debulking surgery specimens of stage IIIC to IV tubo-ovarian high-grade serous carcinoma. Patients and Methods A six-tier histopathologic scoring system was proposed and applied to a test cohort (TC) of 62 patients treated with neoadjuvant chemotherapy and interval debulking surgery. Adnexal and omental sections were independently scored by three pathologists. On the basis of TC results, a three-tier chemotherapy response score (CRS) system was developed and applied to an independent validation cohort of 71 patients. Results The initial system showed moderate interobserver reproducibility and prognostic stratification of TC patients when applied to the omentum but not to the adnexa. Condensed to a three-tier score, the system was highly reproducible (kappa, 0.75). When adjusted for age, stage, and debulking status, the score predicted progression-free survival (PFS; score 2 v 3; median PFS, 11.3 v 32.1 months; adjusted hazard ratio, 6.13; 95% CI, 2.13 to 17.68; P &lt; .001). The three-tier CRS system applied to omental samples from the validation cohort showed high reproducibility (kappa, 0.67) and predicted PFS (CRS 1 and 2 v 3: median, 12 v 18 months; adjusted hazard ratio, 3.60; 95% CI, 1.69 to 7.66; P &lt; .001). CRS 3 also predicted sensitivity to first-line platinum therapy (94.3% negative predictive value for progression &lt; 6 months). A Web site was established to train pathologists to use the CRS system. Conclusion The CRS system is reproducible and shows prognostic significance for high-grade serous carcinoma. Implementation in international pathology reporting has been proposed by the International Collaboration on Cancer Reporting, and the system could potentially have an impact on patient care and research.
Molecular MR imaging of liver fibrosis: A feasibility study using rat and mouse models
Authors: Miloslav Polasek, Bryan C. Fuchs, Ritika Uppal, Daniel T. Schühle, Jamu K. Alford, Galen S. Loving, Suguru Yamada, Lan Wei, Gregory Y. Lauwers, Alexander R. Guimaraes, Kenneth K. Tanabe, Peter Caravan
Journal: Journal of Hepatology (2012)
Trade-offs, the allocation of reproductive effort, and the evolutionary psychology of human mating
Authors: Steven W. Gangestad, Jeffry A. Simpson
Journal: Behavioral and Brain Sciences (2000)

This response reinforces several major themes in our target article: (a) the importance of sex-specific, within-sex variation in mating tactics; (b) the relevance of optimality thinking to understanding that variation; (c) the significance of special design for reconstructing evolutionary history; (d) the replicated findings that women's mating preferences vary across their menstrual cycle in ways revealing special design; and (e) the importance of applying market phenomena to understand the complex dynamics of mating. We also elaborate on three points: (1) Men who have indicators of genetic fitness may provide more direct benefits when female demand for extra-pair and short-term sex is very low; (2) both men and women track ecological cues to make mating decisions; and (3) more research on female orgasm is needed.
The impact of acute kidney injury in cirrhosis: does definition matter?
Authors: Cynthia Tsien, Florence Wong
Journal: Gut (2013)

The definition of renal dysfunction in cirrhosis is undergoing some changes in recent times.1 Although the definition of hepatorenal syndrome2 has served the hepatology community very well by identifying patients with cirrhosis, who are severely ill with advanced kidney failure in the presence of liver failure, many of these patients are so ill that they are no longer responsive to our currently available therapies for hepatorenal syndrome. Therefore, it was proposed that the definition of renal dysfunction in cirrhosis should be modified adapting to the guidelines proposed by the acute kidney injury (AKI) network.3 The proposed definition allows for a diagnosis of AKI whenever there is either a rise in serum creatinine by 0.3 mg/dl in <48 h or a rise by 50% from baseline. Using this new definition, many patients …