tbuckley/cabot-search huggingface dataset:
Transmission of Retroviruses from Seronegative Donors by Transfusion during Cardiac Surgery
Authors: Kenrad E. Nelson, James G. Donahue, Alvaro Muñoz, Noah D. Cohen, Paul M. Ness, Anita Teague, Veronica A. Stambolis, David H. Yawn, Betty Callicott, Hugh McAllister, Bruce A. Reitz, Helen Lee, Homayoon Farzadegan, Charles G. Hollingsworth
Journal: Annals of Internal Medicine (1992)

▪Objective: To evaluate the effectiveness of serologic testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types I and Il (HTLV-I/II) infections and to estimate the risk for transmission of HIV-1 and HTLV-I/II by transfusion of seronegative blood from screened donors. ▪Design: A prospective multicenter cohort study of cardiac surgery patients who received multiple transfusions between 1985 and 1991. ▪Setting: Cardiac surgery services of three large tertiary care hospitals. ▪Patients: The study included 11 532 patients in three hospitals who had cardiovascular surgery. ▪Measurements: Incident HIV-1 and HTLV-I or HTLV-II infection. ▪Results: We detected two new HIV-1 infections among patients transfused with 120 312 units of blood components from seronegative donors. In each case a donor was detected on follow-up who had seroconverted since the donation. The HIV-1 infection rate was 0.0017% with an upper limit of the 95% Cl of 0.0053%. Before donor screening for HTLV-I, transfusion of 51 026 units resulted in two HTLV-I infections (0.0039%) and four HTLV-II infections (0.0078%). After HTLV-I screening was instituted, one recipient was infected with HTLV-II among participants exposed to 69 272 units, a rate of 0.0014%. A corresponding HTLV-l/ll-infecteddonor was found for this patient. ▪Conclusion: Serologic screening of donors for antibodies to HIV-1 and HTLV-I coupled with exclusion of donors from groups having a relatively high risk for infection has led to a low incidence of transfusion-transmittedHIV-1 and HTLV-I/II infection in the United States. A small risk remains, however, despite these measures. We estimate the residual risk for HIV-1 and HTLV-II infection from transfusion of screened blood during the time of this study to be about 1 in 60 000 units.
The Effect of Donor Gender on Graft Survival
Authors: Martin Zeier, Bernd Do[Combining Diaeresis]hler, Gerhard Opelz, Eberhard Ritz
Journal: Journal of the American Society of Nephrology (2002)

Differences in actuarial graft survival according to donor gender have been reported for renal allografts and for cardiac and hepatic allografts, but for the latter in small series with limited biostatistical power. Using the large database of the Collaborative Transplant Study (CTS), this study is an evaluation of graft survival according to donor and recipient gender for renal (n = 124,911), cardiac (n = 25,432), and hepatic (n = 16,410) transplants. Confounders, such as calendar year, geographical area, race, donor and recipient age, HLA mismatch, cold ischemia time, and others, as well as interaction terms were taken into consideration. Death-censored actuarial renal allograft survival from female compared with male donors was less in female recipients and even more so in male recipients. The donor gender-associated risk ratio for graft loss was 1.15 in female recipients and 1.22 in male recipients. The age-gender interaction term was statistically significant, the gender effect being more pronounced for younger (16 to 45 yr) compared with older (>45 yr) donors. Serum creatinine concentrations 1 yr after transplantation were also higher for recipients with kidney grafts coming from female donors irrespective of recipient gender. For first cardiac transplants, graft survival was inferior when the donor was female and the recipient male, but no statistical difference according to donor gender was demonstrable in female recipients. For first hepatic transplants overall, no significant differences according to donor gender were noted. The proportion of recipients who had treatment for rejection crisis during the first year was higher for male recipients of kidneys from female donors compared with male donors. No difference according to donor gender was demonstrable in female recipients. For cardiac and hepatic grafts, no significant effect of donor gender on the proportion of patients treated for rejection episodes was noted. The data show that adverse effects of female donor gender for different organs is much less uniform than reported in the past. An important confounder is donor age. A gender effect on graft survival is also observed for cardiac allografts. Therefore, in addition to potential "nephron underdosing," further pathomechanisms must play a role, possibly differences in immunogenicity according to donor gender.
Antibody-Drug Conjugates Designed to Eradicate Tumors with Homogeneous and Heterogeneous Expression of the Target Antigen
Authors: Yelena V. Kovtun, Charlene A. Audette, Yumei Ye, Hongsheng Xie, Mary F. Ruberti, Sara J. Phinney, Barbara A. Leece, Thomas Chittenden, Walter A. Blättler, Victor S. Goldmacher
Journal: Cancer Research (2006)

Abstract Conjugates of the anti-CanAg humanized monoclonal antibody huC242 with the microtubule-formation inhibitor DM1 (a maytansinoid), or with the DNA alkylator DC1 (a CC1065 analogue), have been evaluated for their ability to eradicate mixed cell populations formed from CanAg-positive and CanAg-negative cells in culture and in xenograft tumors in mice. We found that in culture, conjugates of either drug killed not only the target antigen-positive cells but also the neighboring antigen-negative cells. Furthermore, we showed that, in vivo, these conjugates were effective in eradicating tumors containing both antigen-positive and antigen-negative cells. The presence of antigen-positive cells was required for this killing of bystander cells. This target cell–activated killing of bystander cells was dependent on the nature of the linker between the antibody and the drug. Conjugates linked via a reducible disulfide bond were capable of exerting the bystander effect whereas equally potent conjugates linked via a nonreducible thioether bond were not. Our data offer a rationale for developing optimally constructed antibody-drug conjugates for treating tumors that express the target antigen either in a homogeneous or heterogeneous manner. (Cancer Res 2006; 66(6): 3214-21)
Prevention of lethal murine graft versus host disease by treatment of donor cells with L-leucyl-L-leucine methyl ester.
Authors: M Charley, D L Thiele, M Bennett, P E Lipsky
Journal: Journal of Clinical Investigation (1986)

Graft vs. host disease (GVHD) remains one of the main problems associated with bone marrow transplantation. The current studies were undertaken to determine whether treatment of the donor inoculum with the anticytotoxic cell compound L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) would alter the development of GVHD in a murine model. Irradiated recipient mice transplanted with a mixture of control bone marrow and spleen cells from naive semiallogeneic donors died rapidly from GVHD, whereas the recipients of cells incubated with 250 microM Leu-Leu-OMe all survived. In addition, Leu-Leu-OMe treatment of cells obtained from donors immunized against host alloantigens resulted in significantly prolonged survival. Phenotypic characterization of spleen cells from the various groups of mice that had received Leu-Leu-OMe-treated cells and survived consistently revealed the donor phenotype. Treatment of marrow cells with 250 microM Leu-Leu-OMe appeared to have no adverse effects on stem cell function. Erythropoiesis was undiminished, as assayed by splenic 5-iodo-2'-deoxyuridine-125I uptake. Moreover, granulocytic and megakaryocytic regeneration were histologically equivalent in the spleens of recipients of control or Leu-Leu-OMe-treated cells. Treatment of the donor inoculum with Leu-Leu-OMe thus prevents GVHD in this murine strain combination with no apparent stem cell toxicity.
Inhibition of Murine Prostate Tumor Growth and Activation of Immunoregulatory Cells With Recombinant Canarypox Viruses
Authors: T. S. Griffith, M. Kawakita, J. Tian, J. Ritchey, J. Tartaglia, I. Sehgal, T. C. Thompson, W. Zhao, T. L. Ratliff
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Immunization with modified tumor cells carrying recombinant immunomodulatory genes is being explored as cancer immunotherapy. In this study, we examine whether canarypox ALVAC viruses carrying immunostimulatory cytokine genes (granulocyte–macrophage colony-stimulating factor, interleukin 2, interleukin 12, and tumor necrosis factor-α) can induce antitumor immunity (to rechallenge) in the RM-1 model of a highly aggressive, weakly immunogenic murine prostate cancer. Methods: For antitumor activity studies, RM-1 murine prostate cancer cells were infected with the parental ALVAC virus or one or two recombinant ALVAC–cytokine viruses and then injected into male C57BL/6 mice. For rechallenge studies, other mice were first given an injection subcutaneously with irradiated (nonproliferating) recombinant ALVAC-infected RM-1 cells and then (10 days later) with untreated RM-1 cells. For the determination of which immune cells were required for antitumor activity, mice were immunodepleted of CD4, CD8, or natural killer (NK) NK1.1 cells with the corresponding monoclonal antibodies and were then given an injection of ALVAC–cytokine-infected RM-1 cells. For all experiments, tumor outgrowth and animal survival were monitored. Results: After subcutaneous injection into mice, RM-1 cells infected with one (except ALVAC–interleukin 2) or two ALVAC–cytokine recombinants had statistically significantly greater antitumor activity than RM-1 cells infected with parental ALVAC (P<.001 for all; two-sided test). The antitumor activity of RM-1 cells infected with any two ALVAC–cytokine recombinants was greater than, but not statistically significantly different from, that of RM-1 cells infected with any one ALVAC–cytokine recombinant. NK1.1 cells were necessary for antitumor activity, but tumor-specific CD4+ regulatory T cells were also induced that inhibited CD8+ RM-1-specific cytotoxic T cells, resulting in the lack of immunity to a rechallenge by RM-1 cells. Discussion: Canarypox viruses can transfer immunostimulatory cytokine genes into RM-1 prostate cancer cells. When such cells were injected into mice, the cytokines induced an antitumor response against this highly aggressive, weakly immunogenic tumor. This response, however, did not protect the mouse against a rechallenge with RM-1 cells because suppressor CD4+ T cells were induced that inhibited tumor-specific CD8+ cytotoxic T cells.
Stimulus-response curves for hypoxic pulmonary vasoconstriction in piglets
Authors: D. D. Canniere, C. Stefanidis, R. Hallemans, M. Delcroix, S. Brimioulle, R. Naeije
Journal: Cardiovascular Research (1992)

Objective: The aim was to characterise stimulus-response curves for hypoxic pulmonary vasoconstriction and to observe the effects of drugs reputed to enhance it: aspirin (a cyclo-oxygenase inhibitor), and doxapram (a peripheral chemoreceptor agonist). Methods: Mean pulmonary artery pressure (Ppa) versus fraction of inspired O2 (FIO2) relationships were studied in 18 intact anaesthetised piglets, before and after the intravenous administration, in random order, of either physiological saline, 1 g aspirin, or 20 mg·kg−1 doxapram. Cardiac output (Q) was kept constant, to avoid passive Q dependent changes in Ppa. Results: A progressive decrease in FIO2 from 100% to 12% was associated with an average increase in Ppa from 19 to 38 mm Hg (p<0.001). When FIO2 was further decreased to 8%, Ppa decreased to 32 mm Hg (p<0.01). This stimulus-response curve was unaffected by saline, but displaced in a non-PO2−dependent manner to higher Ppa by doxapram and by aspirin. Conclusions: The pulmonary vascular response to inspiratory hypoxia in intact anaesthetised piglets is biphasic, with a maximum at an FIO2 of 12%. Neither aspirin nor doxapram affect the shape of this stimulus-response curve, and in particular do not prevent low FIO2 associated inhibition of hypoxic pulmonary vasoconstriction. Cardiovascular Research 1992;26:944–949
Lifetime injury prevention: the sport profile model: Figure 1
Authors: Nick Webborn
Journal: British Journal of Sports Medicine (2012)

Participation in sporting activities carries an injury risk. Conversely, the increased awareness that physical inactivity is a major risk factor for disease has led government agencies and the medical community to encourage increased levels of physical activity. Many people will achieve this through participation in sport. Injury inevitably leads to a reduction in participation on a temporary or permanent basis, but the injury experience may also influence the lifelong physical activity behaviour. Few studies adequately examine the possible long-term consequences of sport participation after the competitive period has been completed, but by understanding the patterns of injuries in different sports one test can develop strategies to prevent and better manage the conditions that occur and promote lifelong physical activity. There is a need to develop models of understanding of injury risk at different life phases and levels of participation in a specific sport. The risk assessment of sport participation has to be relevant to a particular sport, the level of participation, skill, age and potential future health consequences. This article describes a sport-specific model which will improve guidance for coaches and healthcare professionals. It poses questions for sports physicians, healthcare providers, educators and for governing bodies of sports to address in a systematic fashion. Additionally the governing body, as an employer, will need to meet the requirements for risk assessment for professional sport and its ethical responsibility to the athlete.
Haplotypes of G Protein–coupled Receptor 154 Are Associated with Childhood Allergy and Asthma
Authors: Erik Melén, Sara Bruce, Gert Doekes, Michael Kabesch, Tarja Laitinen, Roger Lauener, Cecilia M. Lindgren, Josef Riedler, Annika Scheynius, Marianne van Hage-Hamsten, Juha Kere, Göran Pershagen, Magnus Wickman, Fredrik Nyberg
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Allergic diseases are influenced by both genes and environment. A 70-kb haplotype block in the G protein-coupled receptor for asthma susceptibility gene (GPR154; alias GPRA) on chromosome 7p was recently identified to influence susceptibility to asthma and elevated total serum IgE levels in adults.To assess the impact of GPR154 on childhood allergic disease, including allergic sensitization, asthma, and rhinoconjunctivitis, in study populations with diverse environmental backgrounds.We studied farm children, Steiner school children, and two reference groups from five Western European countries in the cross-sectional PARSIFAL (Prevention of Allergy Risk factors for Sensitization In children related to Farming and Anthroposophic Lifestyle) study and a sample of children from the Swedish birth cohort study BAMSE. DNA samples from 3,113 PARSIFAL and 800 BAMSE children were genotyped for 7 GPR154 polymorphisms and haplotypes were inferred. The proportions of alleles and haplotypes (H1-H7) were compared in affected children with their healthy counterparts.Data indicate a global association of the haplotype block to sensitization (allergen-specific serum IgE > or = 0.35 kU/L, p = 0.022), with significant haplotype-specific associations for H1, H5, and H6. Haplotypes H1 and H5 were also significantly associated with childhood allergic asthma (p = 0.045 and p = 0.023, respectively), and H5 to asthma regardless of sensitization. A broader involvement of GPR154 in allergic diseases was further supported in allergic rhinoconjunctivitis (H3: p = 0.046). The associated haplotypes could be allocated into risk (H5/H6) and nonrisk (H1/H3) groups, a pattern supported by allelic association of single nucleotide polymorphisms (SNPs) rs324384 and rs324396.Our results indicate that polymorphisms and haplotypes in the haplotype block of GPR154 are associated with asthma, rhinoconjunctivitis, and sensitization in European children.
Role of the major histocompatibility complex in T cell activation of B cell subpopulations. Major histocompatibility complex-restricted and -unrestricted B cell responses are mediated by distinct B cell subpopulations
Authors: Y Asano, A Singer, RJ Hodes
Journal: The Journal of Experimental Medicine (1981)

The present study has evaluated the identity of the B cell subpopulations participating in T dependent antibody responses that differ in their requirements for major histocompatibility complex-restricted T cell recognition. In vitro responses of keyhole limpet hemocyanin (KLH)-primed T cells and trinitrophenyl (TNP)-primed B cells were studied to both low and high concentrations of the antigen TNP-KLH. It was first demonstrated that for responses to low concentrations of TNP-KLH, (A x B)F(1) {arrow} parent(A) chimeric helper T cells were restricted in their ability to recognize parent(A) but not parent(B) H-2 determinants expressed by both B cells and antigen-presenting cells (APC). In contrast, at higher antigen concentrations, helper T cells were not restricted in their interaction with B cells. It was then determined whether these observed differences in T cell recognition resulted from the activation of distinct B cell subpopulations with different activation requirements. At low concentrations of TNP-KLH it was demonstrated that Lyb-5(-) B cells were activated, and that it was thus the activation of the Lyb-5(-) subpopulation that required T cell recognition of B cell H-2 under these conditions. In contrast, responses to high concentration of antigen required the participation of Lyb-5(+) B cells, and these Lyb-5(+) B cells were activated by a pathway that required H-2- restricted T cell interaction with APC, but not with B cells. The findings presented here have demonstrated that Lyb-5(-) and Lyb-5(+) B cells constitute B cell subpopulations that differ significantly in their activation requirements for T cell-dependent antibody responses to TNP-KLH. In so doing, these findings have established that the function of genetic restrictions in immune response regulation is critically dependent upon the activation pathways employed by functionally distinct subpopulations of B, as well as T, lymphocytes.
Cartilage metabolism in the injured and uninjured knee of the same patient.
Authors: L Dahlberg, H Roos, T Saxne, D Heinegard, M W Lark, L A Hoerrner, L S Lohmander
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVE--To examine if unilateral knee injury affects the synovial fluid concentrations of aggrecan fragments, cartilage oligomeric matrix protein (COMP) fragments, stromelysin-1, and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the contralateral uninjured knee. METHODS--Synovial fluids from the injured and uninjured knees were obtained at different times in a group of patients after unilateral knee trauma. Serum samples were obtained on the same occasion. Concentrations of aggrecan fragments were determined by precipitation with Alcian Blue; those of COMP fragments, stromelysin-1, and TIMP-1 were measured by immunoassay. Concentrations were compared with those in a reference group of 10 healthy volunteers. RESULTS--Immediately after knee injury, concentrations of aggrecan fragments, COMP fragments, stromelysin-1 and TIMP-1 were increased in the synovial fluid of the injured knee. However, concentrations of aggrecan and COMP fragments, and stromelysin-1 increased also in the contralateral uninjured knee immediately after injury, but less than in the injured knee. Subsequently, the concentrations of all markers decreased in the synovial fluid of the injured knee, but remained unchanged in the uninjured knee. The concentration of aggrecan fragments in the injured knee decreased to less than that in the uninjured knee in the chronic phase. Serum concentrations of COMP were much smaller than those in synovial fluid. CONCLUSIONS--The increased concentrations of aggrecan and COMP fragments and stromelysin-1 in the joint fluid of the contralateral, uninjured knee following unilateral knee injury, compared with concentrations in healthy reference knees, suggest changes in joint cartilage metabolism in both knees following unilateral knee injury. The mechanisms for these changes are unclear. The low serum concentration of COMP makes it less likely that there is any significant 9exchange9 of molecular makers between the knees. A further consequence of these findings is that the contralateral knee cannot be recommended as the only control joint in studies of matrix metabolism in patients with unilateral knee injury.
Hormone receptors of the baboon cardiovascular system. Biochemical characterization of aortic and myocardial cytoplasmic progesterone receptors.
Authors: A L Lin, H C McGill, S A Shain
Journal: Circulation Research (1982)

We used the synthetic progestin R5020 (17 alpha, 21-dimethyl-19-norpregna-4,9-diene-3,20-dione) to characterize cytoplasmic progesterone receptors in baboon (Papio sp.) aorta and myocardium. The relative ability of selected steroids to inhibit binding of radiolabeled R5020 to aortic cytoplasmic progesterone receptors was radioinert R5020, 1.0; progesterone, 0.31; triamcinolone acetonide, 0.06; testosterone, 0.002; estradiol-17 beta, 0.01; and cortisol. 0.001. The relative ability of these same steroids to inhibit binding of radiolabeled R5020 to myocardial cytoplasmic progesterone receptors was, respectively, 1.0, 0.58, 0.21, 0.01, 0.01, and 0.001. Both aortic and myocardial cytoplasmic progesterone receptors migrated as macromolecules with a sedimentation coefficient of 8-9S on low ionic strength linear sucrose gradients. Cytoplasmic binding of R5020 was inactivated by incubation of 37 degrees C. Saturation analysis at 2 degrees C showed aorta and myocardium, respectively, contained 41.6 +/- 16.1 (mean +/- SD) and was 14.0 +/- 2.8 fmol R5020 binding sites/mg cytosol protein. The dissociation constant for R5020 was 2.8 +/- 1.2 nM, aorta, and 2.0 +/- 1.1 nM, myocardium. The presence of progesterone receptors in baboon cardiovascular tissues suggests that progestins may directly influence cardiovascular tissue function.
Clinical Care and Health Disparities
Authors: B. Starfield, J. Gérvas, D. Mangin
Journal: Annual Review of Public Health (2012)

Health disparities, also known as health inequities, are systematic and potentially remediable differences in one or more aspects of health across population groups defined socially, economically, demographically, or geographically ( 88 ). This topic has been the subject of research stretching back at least decades. Reports and studies have delved into how inequities develop in different societies and, with particular regard to health services, in access to and financing of health systems. In this review, we consider empirical studies from the United States and elsewhere, and we focus on how one aspect of health systems, clinical care, contributes to maintaining systematic differences in health across population groups characterized by social disadvantage. We consider inequities in clinical care and the policies that influence them. We develop a framework for considering the structural and behavioral components of clinical care and review the existing literature for evidence that is likely to be generalizable across health systems over time. Starting with the assumption that health services, as one aspect of social services, ought to enhance equity in health care, we conclude with a discussion of threats to that role and what might be done about them.