tbuckley/cabot-search huggingface dataset:
Relationship Between Gestational Diabetes Mellitus and Low Maternal Birth Weight
Authors: Giuseppe Seghieri, Roberto Anichini, Alessandra De Bellis, Lorenzo Alviggi, Flavia Franconi, Maria Cristina Breschi
Journal: Diabetes Care (2002)

To study the relationship between low birth weight and the presence of gestational diabetes mellitus (GDM) or peripheral insulin resistance during pregnancy.We studied the relationship between peripheral insulin sensitivity (calculated by Matsuda and DeFronzo's oral glucose tolerance test (OGTT)-derived insulin sensitivity index [ISI(OGTT)]) or GDM prevalence and birth weight in 604 pregnant women, classified as normally glucose tolerant (n = 462) or affected with GDM (n = 142) after a 100-g 3-h oral glucose tolerance test. We then categorized these subjects into two groups: individuals with birth weight in the <10th percentile (<2,600 g; n = 68) and individuals with birth weight in the >10th percentile (n = 536).GDM prevalence was higher in the group in the lowest birth weight decile (<2,600 g; 24/68; 35%) than in the group with normal/high birth weight (118/536; 22%; chi(2) = 5.917; P = 0.01). Relative risk for GDM adjusted for age, parity, family history of diabetes, and prepregnancy body weight was about twofold in the group with low birth weight (odds ratio = 1.89 [95% CI 1.088-3.285; P = 0.023]), and the prevalence of low birth weight was about threefold higher in the first ISI(OGTT) decile. In 450 women whose newborn's weight was known, the delivery of macrosomic babies was associated with a twofold higher relative risk for GDM in women who themselves had low birth weight. In the latter, the relationships between their newborn's weight and either maternal glucose tolerance (positive) or ISI(OGTT) (negative) were amplified.Low maternal birth weight was associated with a twofold higher risk for GDM, independent of major confounders. Such a risk was highest in women with low birth weight who delivered macrosomic babies, and in the group with low birth weight, the relationship between maternal glucose tolerance or insulin resistance and offspring's neonatal weight was much more evident.
Immunoregulatory circuits that modulate responsiveness to suppressor cell signal. Failure of B10 mice to respond to suppressor factors can be overcome by quenching the contrasuppressor circuit.
Authors: K Yamauchi, D R Green, D D Eardley, D B Murphy, R K Gershon
Journal: The Journal of Experimental Medicine (1981)

The in vitro antibody response of spleen cells from B10 strain mice is not suppressed by factor preparations made by primed Ly-2 T cells, although these preparations can suppress the in vitro antibody response of spleen cells from other mouse strains (1-3)2. The factor preparations from Ly-2 cells contain at least two separable activities: one that acts as a suppressor moiety (Ly-2 T cell suppressor factor [Ly-2 TsF]) and a second factor that acts as an inducer of contrasuppression (Ly-2 TcsiF); the latter initiates a series of cellular interactions that leads to the inhibition of suppression that we refer to as contrasuppression. Removal of components (either cellular or humoral) of the contrasuppressor circuit makes spleen cells from B10 strain mice as easily suppressible as are those of other mouse strains. Thus, removal of the contrasuppressor inducer cell and/or its biologically active product with the use of an anit-J serum, or removal of the functional acceptor of the inducer cell with the same or other (Ly-2; Qa-1) antisera breaks the B10 suppressor barrier. Contrasuppressive activity. but not helper activity can be eluted from anit-I-J immunoabsorbents. The addition of B10 T cells to either B6 or B10 spleen cell culture deprived of acceptor cells for the TcsiF reconstitutes contrasuppression more efficiently than does the addition of C57BL/6 T cells. Ly-2 TcsiF is more cross-reactive than is Ly-2 TsF so that absorption of factor preparations from sheep erythrocyte-primed Ly-2 cells with horse erythrocytes also breaks the B10 suppressor barrier. The hyperresponsiveness of splenic T cells from B10 strains to Ly-2 TcsiF may be an in vitro exaggeration of a normal in vivo process. Thus it is possible that one can take advantage of this unusual situation to help dissect out the cellular and subcellular components of T cell circuits that moldulate sensitivity to immunoregulatory signals.
Gene Dose–Dependent Maturation and Receptor Editing of B Cells Expressing Immunoglobulin (Ig)g1 or Igm/Igg1 Tail Antigen Receptors
Authors: Sarah L. Pogue, Christopher C. Goodnow
Journal: The Journal of Experimental Medicine (2000)

Conserved differences between the transmembrane and cytoplasmic domains of membrane immunoglobulin (Ig)M and IgG may alter the function of antigen receptors on naive versus memory B cells. Here, we compare the ability of these domains to signal B cell allelic exclusion and maturation in transgenic mice. A lysozyme-binding antibody was expressed in parallel sets of mice as IgM, IgG1, or a chimeric receptor with IgM extracellular domains and transmembrane/cytoplasmic domains of IgG1. Like IgM, the IgG1 or chimeric IgM/G receptors triggered heavy chain allelic exclusion and supported development of mature CD21+ B cells. Many of the IgG or IgM/G B cells became CD21high and downregulated their IgG and IgM/G receptors spontaneously, resembling memory B cells and B cells with mutations that exaggerate B cell antigen receptor signaling. Unlike IgM-transgenic mice, “edited” B cells that carry non–hen egg lysozyme binding receptors preferentially accumulated in IgG and IgM/G mice. This was most extreme in lines with the highest transgene copy number and diminished in variant offspring with fewer copies. The sensitivity of B cell maturation to transgene copy number conferred by the IgG transmembrane and cytoplasmic domains may explain the diverse phenotypes found in other IgG-transgenic mouse strains and may reflect exaggerated signaling.
Invariant NKT cells reduce the immunosuppressive activity of influenza A virus–induced myeloid-derived suppressor cells in mice and humans
Authors: Carmela De Santo, Mariolina Salio, S. Hajar Masri, Laurel Yong-Hwa Lee, Tao Dong, Anneliese O. Speak, Stefan Porubsky, Sarah Booth, Natacha Veerapen, Gurdyal S. Besra, Hermann-Josef Gröne, Frances M. Platt, Maria Zambon, Vincenzo Cerundolo
Journal: Journal of Clinical Investigation (2008)

Infection with influenza A virus (IAV) presents a substantial threat to public health worldwide, with young, elderly, and immunodeficient individuals being particularly susceptible. Inflammatory responses play an important role in the fatal outcome of IAV infection, but the mechanism remains unclear. We demonstrate here that the absence of invariant NKT (iNKT) cells in mice during IAV infection resulted in the expansion of myeloid-derived suppressor cells (MDSCs), which suppressed IAV-specific immune responses through the expression of both arginase and NOS, resulting in high IAV titer and increased mortality. Adoptive transfer of iNKT cells abolished the suppressive activity of MDSCs, restored IAV-specific immune responses, reduced IAV titer, and increased survival rate. The crosstalk between iNKT and MDSCs was CD1d- and CD40-dependent. Furthermore, IAV infection and exposure to TLR agonists relieved the suppressive activity of MDSCs. Finally, we extended these results to humans by demonstrating the presence of myeloid cells with suppressive activity in the PBLs of individuals infected with IAV and showed that their suppressive activity is substantially reduced by iNKT cell activation. These findings identify what we believe to be a novel immunomodulatory role of iNKT cells, which we suggest could be harnessed to abolish the immunosuppressive activity of MDSCs during IAV infection.
Spectrum of psoriatic spondyloarthropathy in a cohort of 100 Spanish patients
Authors: R Queiro
Journal: Annals of the Rheumatic Diseases (2002)

In their initial work, Moll and Wright recognised five patterns of psoriatic arthritis (PsA)—namely, distal joint disease, oligoarthritis, polyarthritis, arthritis mutilans, and spondylitis.1 Although psoriatic spondyloarthropathy was recognised as a specific pattern of PsA, it has become clear that the presence of isolated spondyloarthropathy (SpA) in PsA is unusual, and in most cases, it occurs with peripheral arthritis.2,3 We undertook the present work to analyse the clinical features of our patients with psoriatic SpA and to compare the different subgroups included within the psoriatic SpA spectrum.

One hundred patients with psoriatic SpA, defined in accordance with the European Spondyloarthropathy Study Group (ESSG) criteria,4 were consecutively recruited and their clinical records were analysed in this retrospective cross sectional study. All patients were evaluated according to a standard protocol, and their functional ability was assessed using the Health Assessment Questionnaire-Specific for SpA (HAQ-S).5 We included patients with isolated axial involvement, as well as those with axial plus peripheral disease. The study group was divided according to the articular patterns seen during …
Potentiation of immunomodulatory antibodies with oncolytic viruses for therapy of poorly-immunogenic tumors
Authors: Dmitriy Zamarin, Rikke B Holmgaard, Tamar Plitt, James Allison, Taha Merghoub, Jedd D Wolchok
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Cancer immunotherapy with antibodies targeting immune checkpoints has demonstrated durable clinical benefit, though responses have not been universal and, in particular, not effective for tumors lacking preexisting lymphocytic infiltration. Oncolytic viruses (OV) have recently
First-in-Human Phase I Dose-Escalation Study of the HSP90 Inhibitor AUY922 in Patients with Advanced Solid Tumors
Authors: Cristiana Sessa, Geoffrey I. Shapiro, Kapil N. Bhalla, Carolyn Britten, Karen S. Jacks, Monica Mita, Vali Papadimitrakopoulou, Tim Pluard, Thomas A. Samuel, Mikhail Akimov, Cornelia Quadt, Cristina Fernandez-Ibarra, Hong Lu, Stuart Bailey, Sandra Chica, Udai Banerji
Journal: Clinical Cancer Research (2013)

A phase I study was conducted with the primary objective of determining the maximum tolerated dose (MTD) of AUY922 in patients with advanced solid tumors. Secondary objectives included characterization of the safety, pharmacokinetic, and pharmacodynamic profiles.Patients with advanced solid tumors received 1-hour i.v. infusions of AUY922 once a week in a 28-day cycle. An adaptive Bayesian logistic regression model that employed observed dose-limiting toxicities (DLT) in the first treatment cycle was used to guide dose-escalation decisions, with the established MTD to be used in phase II studies.One hundred and one patients were enrolled and explored at doses in the range of 2 to 70 mg/m(2). DLTs occurred in 8 patients (22-70 mg/m(2)) and included diarrhea, asthenia/fatigue, anorexia, atrial flutter, and visual symptoms. At 70 mg/m(2), the AUY922 concentration achieved was consistent with active concentrations in a range of xenograft models. There was evidence of target inhibition in peripheral blood mononuclear cells (HSP70 induction) and tumor (client protein depletion and reduction of metabolic activity by (18)F-FDG PET). The recommended phase II dose (RP2D) of 70 mg/m(2) was proposed on the basis of toxicity and pharmacokinetic and pharmacodynamic profiles.At the RP2D of 70 mg/m(2), AUY922 exhibited acceptable tolerability, and phase II single-agent and combination studies have been initiated in patients with HER2-positive breast, gastric, and non-small cell lung cancers.
Male Circumcision: A Globally Relevant but Under-Utilized Method for the Prevention of HIV and Other Sexually Transmitted Infections
Authors: Aaron A.R. Tobian, Seema Kacker, Thomas C. Quinn
Journal: Annual Review of Medicine (2013)

Randomized trials have demonstrated that male circumcision (MC) reduces heterosexual acquisition of HIV, herpes simplex virus type 2, human papillomavirus (HPV), and genital ulcer disease among men, and it reduces HPV, genital ulcer disease, bacterial vaginosis, and trichomoniasis among female partners. The pathophysiology behind these effects is multifactorial, relying on anatomic and cellular changes. MC is cost effective and potentially cost saving in both the United States and Africa. The World Health Organization and Joint United Nations Program on HIV/AIDS proposed reaching 80% MC coverage in HIV endemic countries, but current rates fall far behind targets. Barriers to scale-up include supply-side and demand-side challenges. In the United States, neonatal MC rates are decreasing, but the American Academy of Pediatrics now recognizes the medical benefits of MC and supports insurance coverage. Although MC is a globally valuable tool to prevent HIV and other sexually transmitted infections, it is underutilized. Further research is needed to address barriers to MC uptake.
Nonlinear Changes of Transmembrane Potential During Electrical Shocks
Authors: Eric R. Cheek, Vladimir G. Fast
Journal: Circulation Research (2003)

Defibrillation shocks induce nonlinear changes of transmembrane potential (ΔV m ) that determine the outcome of defibrillation. As shown earlier, strong shocks applied during action potential plateau cause nonmonotonic negative ΔV m , where an initial hyperpolarization is followed by V m shift to a more positive level. The biphasic negative ΔV m can be attributable to (1) an inward ionic current or (2) membrane electroporation. These hypotheses were tested in cell cultures by measuring the effects of ionic channel blockers on ΔV m and measuring uptake of membrane-impermeable dye. Experiments were performed in cell strands (width ≈0.8 mm) produced using a technique of patterned cell growth. Uniform-field shocks were applied during the action potential plateau, and ΔV m was measured by optical mapping. Shock-induced negative ΔV m exhibited a biphasic shape starting at a shock strength of ≈15 V/cm when estimated peak ΔV − m was ≈−180 mV; positive ΔV m remained monophasic. Application of a series of shocks with a strength of 23±1 V/cm resulted in uptake of membrane-impermeable dye propidium iodide. Dye uptake was restricted to the anodal side of strands with the largest negative ΔV m , indicating the occurrence of membrane electroporation at these locations. The occurrence of biphasic negative ΔV m was also paralleled with after-shock elevation of diastolic V m . Inhibition of I f and I K1 currents that are active at large negative potentials by CsCl and BaCl 2 , respectively, did not affect ΔV m , indicating that these currents were not responsible for biphasic ΔV m . These results provide evidence that the biphasic shape of ΔV m at sites of shock-induced hyperpolarization is caused by membrane electroporation.
CHEMOTHERAPEUTIC TRIALS IN PSYCHOSIS: I
Authors: WILLIAM J. TURNER, SIDNEY MERLIS
Journal: American Journal of Psychiatry (1956)

In our experience, Frenquel up to 80 mg. t.i.d. had no effect on 17 schizophrenic patients, 2 alcoholics, and 7 psychoneurotic subjects. A trial of pilocarpine at 10 mg. t.i.d. also proved to be without effect on 26 out of 27 subjects.
Murine liver allograft transplantation: Tolerance and donor cell chimerism
Authors: Shigwang Qian, Anthony J. Demetris, Noriko Murase, Abdul S. Rao, John J. Fung, Thomas E. Starzl
Journal: Hepatology (1994)

Nonarterialized orthotopic liver transplantation with no immunosuppression was performed in 13 mouse-strain combinations. Two strain combinations with major histocompatibility complex class I and class II and minor histocompatibility complex disparity had 20% and 33% survival of more than 100 days, but the other 11 combinations, including four that were fully allogeneic and all with only class I, class II or minor disparities, yielded 45% to 100% survival of more than 100 days. Long-living recipients permanently accepted donor-strain heterotopic hearts transplanted on the same day or donor-strain skin 3 mo after liver transplantation, in spite of detectable antidonor in vitro activity with mixed lymphocyte reaction and cellmediated lymphocytotoxicity testing (split tolerance). In further donor-specific experiments, liver grafts were not rejected by presensitized major histocompatibility complex class I-disparate recipients and they protected donor-strain skin grafts from second set (or any) rejection. Less frequently, liver transplantation rescued rejecting skin grafts placed 1 wk earlier in major histocompatibility complex class I, class II and minor histocompatibility complex, class II or minor histocompatibility complex-disparate strain combinations. Donor-derived leukocyte migration to the central lymphoid organs occurred within 1 to 2 hr after liver transplantation in all animals examined, persisted in the surviving animals until they were killed (&gt;375 days), and was demonstrated with double-immunolabeling to be multilineage. The relation of these findings to so-called hepatic tolerogenicity and to tolerance in general is discussed. (Hepatology 1994;19:916-924.)
Experimental pain models and clinical chronic pain: Is plasticity enough to link them?
Authors: Paolo Marchettini, Marco Lacerenza, Fabio Formaglio
Journal: Behavioral and Brain Sciences (1997)

The central hyperexcitability observed in animal models supports a pathophysiological explanation for chronic human pain. Novel information on cholecystokinin (CCK) upregulation offers a rationale for reduced opioid response in neuropathic pain. However, the basic information provided by scientists should not lead clinicians to equate experimental models to chronic human conditions. Clinicians should provide careful reports and attempt to classify pathophysiologically clinical conditions that have so far been grouped generically. [blumberg et al.; coderre &amp; katz; dickenson; wiesenfeld-hallin et al.]
Role of C'3 and Fc receptors in B-lymphocyte activation.
Authors: G Möller, A Coutinho
Journal: The Journal of Experimental Medicine (1975)

Attempts were made to identify the non-Ig lymphocyte receptor responsible for B-cell induction by antigen and polyclonal B-cell activators (PBA). As a first step, the role of C'3 and Fc receptors was analyzed. It was shown that complement could be fixed onto B cells to such an extent that the lymphocytes could not bind complement-coated red cells, but this did not result in induction of polyclonal antibody synthesis, nor did it inhibit the lymphocytes response to PBA. However, the C'3 receptros possessed a passive focussing role in the induction of polyclonal antibody responses. Thus, PBA that had fixed complement activated polyclonal responses at lower concentrations than the same substances that had not fixed complement. Most likely the dual binding of PBA molecules to B cells by the PBA and the C'3 receptors caused more PBA molecules to be bound to each cell. However, the focussing function of the C'3 receptors was several orders of magnitude smaller than that of the Ig receptors. Analogous studies were carried out with Fc receptors. Binding of different types of antigen-antibody complexes did not cause activation of polyclonal or specific antibody synthesis, nor did it significantly interfere with induction of antibody synthesis by PBA substances.
Economic recession may have caused 10 000 extra suicides
Authors: A. O'Dowd
Journal: BMJ (2014)

Around 10 000 extra suicides in the Western world from 2008 to 2010 were highly likely to be related to the recent economic recession, a study has concluded.1

The study, by the University of Oxford and the London School of Hygiene and Tropical Medicine, was published in the British Journal of Psychiatry on 12 June. It said that suicide rates had risen significantly across Europe, Canada, and the United States …
Customized Adjuvant Phase II Trial in Patients With Non–Small-Cell Lung Cancer: IFCT-0801 TASTE
Authors: Marie Wislez, Fabrice Barlesi, Benjamin Besse, Julien Mazières, Patrick Merle, Jacques Cadranel, Clarisse Audigier-Valette, Denis Moro-Sibilot, Laure Gautier-Felizot, François Goupil, Aldo Renault, Elisabeth Quoix, Pierre-Jean Souquet, Anne Madroszyck, Romain Corre, David Pérol, Franck Morin, Gérard Zalcman, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2014)

Surgical resection plus adjuvant platinum-based chemotherapy is considered standard care for stage II to III non-small-cell lung cancer (NSCLC), but its efficacy is limited, and it involves toxic risks, justifying patient-tailored treatment. Excision repair cross-complementation group 1 (ERCC1) was shown to predict cisplatin-based chemotherapy response; EGFR mutations were predictive of epidermal growth factor receptor inhibition response.This prospective randomized phase II trial enrolled 150 patients with completely resected non-squamous cell stage II or IIIA (non-N2) tumors. Patients in the control arm (n = 74) were treated with four standard-dose courses of cisplatin plus pemetrexed (CP). In the customized treatment arm (n = 76), patients with activated EGFR mutations received erlotinib 150 mg for 1 year; ERCC1-negative patients received four CP courses, whereas ERCC1-positive patients underwent follow-up. The trial sought to demonstrate the feasibility of customized adjuvant chemotherapy based on timely biomarker analysis within a 2-month postsurgery delay. Secondary objectives were tolerability, compliance with adjuvant therapy, and biomarker distribution.In arm A, all patients received CP; in arm B, seven received erlotinib, 53 were administered CP, and 16 underwent follow-up. Median erlotinib exposure was 344 days. Of the 127 patients allocated to CP, 82% received four cycles with good tolerability. The overall success rate of the trial (ie, percentage of patients with complete biomarker status able to start adjuvant treatment within 2 months of surgery) was 80%.The primary end point of the trial was met, demonstrating the feasibility of a national biology-driven trial in the adjuvant NSCLC setting. Nevertheless, the phase III part was canceled because of the unreliability of the ERCC1 immunohistochemical readouts.