tbuckley/cabot-search huggingface dataset:
Selecting B cells and plasma cells to memory
Authors: Thomas Dörner, Andreas Radbruch
Journal: The Journal of Experimental Medicine (2005)

Humoral immunity appears to be based on immunological memory provided by memory plasma cells, which secrete protective antibodies, and memory B cells, which react to antigen challenge by differentiating into plasma cells. How these differentiation pathways relate to each other, how cells are selected into these memory populations, and how these populations are maintained remains enigmatic.
THE EFFECT OF HEMATIN ON THE CIRCULATION AND RESPIRATION
Authors: Wade H. Brown, A. S. Loevenhart
Journal: The Journal of Experimental Medicine (1913)

1. Doses of less than six milligrams of hematin and, under certain conditions, larger doses may cause a slight rise of blood pressure. 2. Large doses of hematin cause a profound and prolonged fall of blood pressure. The principal factor in this fall of blood pressure is the marked dilatation of the splanchnic vessels. The splanchnic dilatation either does not occur at all or but very slightly if the splanchnic nerves are cut. The splanchnic dilatation is partly compensated for by a marked constriction of cutaneous vessels and it seems probable that the cutaneous constriction is active and not simply passive to the splanchnic engorgement. 3. Hematin acts upon the cardio-inhibitory center causing a marked slowing of the rate of heart-beat, and in large doses produces a typical vagal pulse or even marked irregularities in the amplitude and rhythm of the pulse. Under hematin the heart at first shows great loss of tone but later the tone increases beyond the normal. The cardiac output for a time is greatly diminished. 4. In the large doses employed by us, hematin depresses the respiratory center and death under hematin is due to paralysis of this center.
Dactylitis in psoriatic arthritis: a marker for disease severity?
Authors: J E Brockbank
Journal: Annals of the Rheumatic Diseases (2004)

To describe dactylitis in a large cohort of patients with psoriatic arthritis followed prospectively in a specialist clinic, and identify whether it is associated with a worse prognosis.Between 1979 and 1999, 537 patients were registered in the psoriatic arthritis clinic and entered onto a longitudinal database. Patients were followed prospectively at six to 12 month intervals according to a standard protocol, and all information was entered onto a database. The database was searched for patients with dactylitis. Descriptive statistics were used to describe the population and chi(2) tests to relate dactylitis to radiographic changes.Dactylitis was documented in 260 patients (48%); 69% of the episodes were recorded at presentation to the clinic. Dactylitis affected feet only in 65% of cases, hands only in 24%, and both hands and feet in 12%. Recurrent dactylitis occurred in 44% of the patients. Increased radiological progression was noted in digits showing dactylitis compared with those without dactylitis (50% v 38%, respectively; p<0.0001).Dactylitis is common among patients with psoriatic arthritis. It most often affects the feet, in an asymmetrical distribution. It is associated with a greater degree of radiological damage than occurs in digits not affected by dactylitis.
Asymmetric Dimethylarginine Predicts Cardiovascular Events in Patients With Type 2 Diabetes
Authors: Katarzyna Krzyzanowska, Friedrich Mittermayer, Michael Wolzt, Guntram Schernthaner
Journal: Diabetes Care (2007)

Circulating concentrations of an endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are elevated in patients with increased cardiovascular risk. We hypothesized that ADMA predicts cardiovascular events and enhances risk prediction independent of established risk markers in patients with type 2 diabetes.This prospective cohort study included 125 patients with type 2 diabetes. ADMA, L-arginine, high-sensitivity C-reactive protein (CRP), and routine clinical parameters were determined at baseline. First occurrence of cardiovascular events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, carotid revascularization, or all-cause mortality) was defined as a composite end point.During a median follow-up of 21 (interquartile range 11-27) months, 84 events occurred in 48 patients. According to multivariate Cox regression analysis, patients with baseline ADMA or CRP in the highest tertile had a significantly increased hazard ratio for incident cardiovascular events compared with those with ADMA or CRP in tertile 1 (2.37 [95% CI 1.05-5.35], P = 0.038, and 3.63 [1.59-8.28], P = 0.002). Assessing the joint effect of ADMA and CRP revealed that patients with either ADMA or CRP or both in the highest tertile had increased hazard ratios for cardiovascular events compared with patients with neither ADMA nor CRP in the highest tertile before and after adjustment for possible confounders (hazard ratio 4.59 [95% CI 2.07-10.15], P < 0.001).ADMA predicted cardiovascular events and enhanced the predictive role of CRP in patients with type 2 diabetes. ADMA therefore could improve cardiovascular risk assessment in patients with type 2 diabetes.
Susceptibility to tumors induced by polyoma virus is conferred by an endogenous mouse mammary tumor virus superantigen.
Authors: A E Lukacher, Y Ma, J P Carroll, S R Abromson-Leeman, J C Laning, M E Dorf, T L Benjamin
Journal: The Journal of Experimental Medicine (1995)

A dominant gene carried in certain inbred mouse strains confers susceptibility to tumors induced by polyoma virus. This gene, designated Pyvs, was defined in crosses between the highly susceptible C3H/BiDa strain and the highly resistant but H-2k-identical C57BR/cdJ strain. The resistance of C57BR/cdJ mice is overcome by irradiation, indicating an immunological basis. In F1 x C57BR/cdJ backcross mice, tumor susceptibility cosegregates with Mtv-7, a mouse mammary tumor provirus carried by the C3H/BiDa strain. This suggests that Pyvs might encode the Mtv-7 superantigen (SAG) and abrogate polyoma tumor immunosurveillance through elimination of T cells bearing specific V beta domains. DNA typing of 110 backcross mice showed no evidence of recombination between Pyvs and Mtv-7. Strongly biased usage of V beta 6 by polyoma virus-specific CD8+ cytotoxic T lymphocytes in C57BR/cdJ mice implicates T cells bearing this Mtv-7 SAG-reactive V beta domain as critical anti-polyoma tumor effector cells in vivo. These results indicate identity between Pyvs and Mtv-7 sag, and demonstrate a novel mechanism of inherited susceptibility to virus-induced tumors based on effects of an endogenous superantigen on the host's T cell repertoire.
Skin manifestations in acute arsenic poisoning from the Wakayama curry-poisoning incident
Authors: K. Uede, F. Furukawa
Journal: British Journal of Dermatology (2003)

Four people died and 63 others became ill after eating arsenic-laced curry served at a community festival in Wakayama, Japan, on 25 July 1998. Although dermatological manifestations after the acute ingestion of arsenic have seldom been documented, they were observed in 56% of the victims in the Wakayama curry-poisoning incident.To characterize the skin manifestations due to acute arsenic poisoning.Four of the 67 patients with arsenic poisoning died, and the remaining 63 patients served as subjects for this study. The dermatological findings were extracted from the medical charts at the institutions which admitted the victims, and from the results of a medical inquiry and examinations during a health screening 3 months after the incident.Dermatological findings were observed in 56% of the victims during the acute stage of poisoning. Facial oedema was observed in 13 patients, transient flushing erythema in five, conjunctival haemorrhage in 15, maculopapular eruptions in the intertriginous areas in eight, acral desquamation in 11, and herpesvirus infection in three. The histopathological findings of the maculopapular eruptions showed moderate to marked perivascular infiltration with endothelial swelling. Examination of 21 patients at 3 months after their exposure to arsenic revealed ungual changes including Mee's or Beau's lines in 17 cases, periungual pigmentation in nine, and acral desquamation in four cases.Our observations indicate that skin lesions are common in patients with acute arsenic poisoning; these findings may provide information of diagnostic significance.
Disruptive Mood Dysregulation Disorder: A New Diagnostic Approach to Chronic Irritability in Youth
Authors: Amy Krain Roy, Vasco Lopes, Rachel G. Klein
Journal: American Journal of Psychiatry (2014)

Disruptive mood dysregulation disorder (DMDD), a newcomer to psychiatric nosology, addresses the need for improved classification and treatment of children exhibiting chronic nonepisodic irritability and severe temper outbursts. In recent years, many of these children have been diagnosed with bipolar disorder, despite the lack of distinct mood episodes. This diagnostic practice has raised concerns, in part because of the escalating prescription of atypical antipsychotics. This article provides an overview of the limited literature on DMDD, including its history and relevant studies of assessment and treatment. A case study is included to illustrate key points, including diagnostic issues that clinicians may encounter when considering a diagnosis of DMDD.
MicroRNA-133 Controls Vascular Smooth Muscle Cell Phenotypic Switch In Vitro and Vascular Remodeling In Vivo
Authors: Daniele Torella, Claudio Iaconetti, Daniele Catalucci, Georgina M. Ellison, Angelo Leone, Cheryl D. Waring, Angela Bochicchio, Carla Vicinanza, Iolanda Aquila, Antonio Curcio, Gianluigi Condorelli, Ciro Indolfi
Journal: Circulation Research (2011)

MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac muscle biology and pathophysiology. However, their expression and regulation in vascular cell physiology and disease is currently unknown.The aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in vascular smooth muscle cell (VSMC) phenotypic switch in vitro and in vivo.We demonstrate here that miR-133 is robustly expressed in vascular smooth muscle cells (VSMCs) in vitro and in vivo, whereas miR-1 vascular levels are negligible. miR-133 has a potent inhibitory role on VSMC phenotypic switch in vitro and in vivo, whereas miR-1 does not have any relevant effect per se. miR-133 expression is regulated by extracellular signal-regulated kinase 1/2 activation and is inversely correlated with VSMC growth. Indeed, miR-133 decreases when VSMCs are primed to proliferate in vitro and following vascular injury in vivo, whereas it increases when VSMCs are coaxed back to quiescence in vitro and in vivo. miR-133 loss- and gain-of-function experiments show that miR-133 plays a mechanistic role in VSMC growth. Accordingly, adeno-miR-133 reduces but anti-miR-133 exacerbates VSMC proliferation and migration in vitro and in vivo. miR-133 specifically suppresses the transcription factor Sp-1 expression in vitro and in vivo and through Sp-1 repression regulates smooth muscle gene expression.Our data show that miR-133 is a key regulator of vascular smooth muscle cell phenotypic switch in vitro and in vivo, suggesting its potential therapeutic application for vascular diseases.
Does general exercise training before and during pregnancy influence the pelvic floor “opening” and delivery outcome? A 3D/4D ultrasound study following nulliparous pregnant women from mid-pregnancy to childbirth
Authors: Kari Bø, Gunvor Hilde, Jette Stær-Jensen, Franziska Siafarikas, Merete Kolberg Tennfjord, Marie Ellstrøm Engh
Journal: British Journal of Sports Medicine (2014)

It has been suggested that women who are regular exercisers have a tighter pelvic floor and thereby have more difficulty during childbirth than non-exercising women. We investigated whether women exercising before and during pregnancy have a narrower levator hiatus (LH) area than their sedentary counterparts. We also studied whether regular exercise at gestational week 37 influences delivery outcome.Cohort study of 274 nulliparous pregnant women assessed at mid-pregnancy and gestational week 37 by three-dimensional/four-dimensional transperineal ultrasonography of the LH area. Exercisers were defined as those exercising ≥30 min three times per week and non-exercisers as not exercising. Exercise data were collected via electronic questionnaire at mean gestational weeks 21 and 37. Labour and delivery outcomes were collected from the women's electronic medical birth records. Differences between exercisers and non-exercisers were analysed using independent sample t test or χ(2) test. p Value was set to ≤0.05.At gestational week 37, exercisers had a significantly larger LH area than non-exercisers at rest and during PFM contraction (mean difference -1.6 cm(2) (95% CI -3.0 to -0.3), p=0.02 and -1.1 cm(2) (95% CI -2.0 to -0.1), p=0.04, respectively). No significant differences were found between exercisers and non-exercisers at week 37 in any labour or delivery outcomes.The results of the present study do not support the hypothesis that women exercising regularly before or during pregnancy have a narrower LH area or more complicated childbirths than non-exercising women.ClinicalTrials.gov: NCT01045135.
Prevalence of wearing-off and dyskinesia among the patients with Parkinson’s disease on levodopa therapy: a multi-center registry survey in mainland China
Authors: Wei Chen, Qin Xiao, Ming Shao, Tao Feng, Wei-Guo Liu, Xiao-Guang Luo, Xiao-Chun Chen, An-Mu Xie, Chun-Feng Liu, Zhen-Guo Liu, Yi-Ming Liu, Jian Wang, Sheng-Di Chen
Journal: Translational Neurodegeneration (2014)

Chronic levodopa (L-dopa) treatment in Parkinson's disease (PD) is often associated with the development of motor complications, but the corresponding epidemiological data is rare in Chinese PD patients. The present survey was to investigate the prevalence rate of wearing-off (WO) and dyskinesia among the patients with PD in China. From May 2012 to October 2012, a 3-step registry survey for wearing off (WO) and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China. There were 1,558 PD patients fulfilling the inclusion criteria. Among them, 1,051 had at least one positive response of 9-item wearing off questionnaire (WOQ-9), 724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists, respectively. The overall prevalence rates of WO and dyskinesia were 46.5% (95% CI 44.0% - 48.9%) and 10.3% (95% CI 8.8% - 11.8%), respectively. The mean score of WOQ-9 for those with WO was 3.8 (SD = 1.8), with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms. Better improvement of motor symptoms (n = 354, 87.8%) and long-term disease control and drug selection (n = 288, 71.5%) were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO. This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from mainland China. WO prevalence rate among Chinese PD patients was in line with, while dyskinesia prevalence rate was lower than previous reports from other Countries.
Human colorectal mucosal O6-alkylguanine DNA-alkyltransferase activity and DNA-N7-methylguanine levels in colorectal adenoma cases and matched referents
Authors: N P Lees, K L Harrison, C N Hall, G P Margison, A C Povey
Journal: Gut (2006)

O(6)-alkylguanine DNA-alkyltransferase (MGMT) provides protection against alkylating agent-induced GC-->AT transition mutations. Such mutations are frequently seen in the KRAS oncogene of large colorectal adenomas, but whether adenoma or mutational risk in humans is influenced by MGMT activity and alkylating agent exposure is unclear. Hence, MGMT activity and, as an indicator of alkylating agent exposure, DNA-N7-methylguanine (N7-MeG) levels were determined in the normal tissue of patients with and without adenomas.Biopsy specimens of normal colorectal mucosa were collected during colonoscopy from 85 patients with histologically proved colorectal adenomas (cases) and from 85 patients free of gastrointestinal neoplasia (referents) matched by age, sex and biopsy location. MGMT activity and N7-MeG levels were measured in colorectal tissue extracts and DNA, respectively.MGMT activity was higher in the normal mucosa of cases than in referents (6.65+/-3.03 vs 5.61+/-2.74 fmol/micro g DNA, p = 0.01). On stratification of cases, MGMT activity was found to be considerably greater in the normal mucosa of cases with large adenomas (p = 0.003) and slightly higher in cases with a GC-->AT transition mutation in the K-ras gene (p = 0.03). Elevated MGMT levels were associated with an increased risk of adenoma (OR 1.17, 95% CI 1.03 to 1.33 per unit increase in activity). Detectable levels of N7-MeG were found in DNA from 89% of cases and 93% of referents, with levels ranging from <0.1 to 7.7 micro mol/mol dG. Cases and referents had similar DNA-N7-MeG levels.Human exposure to methylating agents is widespread. MGMT activity is increased in the normal mucosa of patients with adenomas.
Prospective Study of a Risk Score in the Prediction of Advanced Colorectal Neoplasia at Colonoscopy
Authors: Ji Chen, Rupert W. Leong
Journal: Clinical Gastroenterology and Hepatology (2013)

We aimed to validate a clinical risk score predictive of risk for advanced colorectal neoplasia in an asymptomatic Australian population, and determine the viability of including body mass index (BMI) and ethnicity in the risk score.
Effect of Glimepiride on Insulin-Stimulated Glycogen Synthesis in Cultured Human Skeletal Muscle Cells
Authors: Axel Haupt, Christiana Kausch, Dominik Dahl, Oliver Bachmann, Michael Stumvoll, Hans-U. Häring, Stephan Matthaei
Journal: Diabetes Care (2002)

OBJECTIVE—To examine the effect of glimepiride on insulin-stimulated glycogen synthesis in cultured human skeletal muscle cells in comparison with glibenclamide. RESEARCH DESIGN AND METHODS—Myotubes derived from glucose-tolerant subjects were incubated with glimepiride or glibenclamide (0–100 μmol/l) for 4 h and with or without insulin (100 nmol/l) for 2 h, and subsequently glycogen synthesis was determined. RESULTS—Glimepiride had no significant effect on basal glycogen synthesis; in contrast, glimepiride caused a dose-dependent increase of insulin-stimulated glycogen synthesis, with a maximal effect of 39.97 ± 8.4% (mean ± SEM, n = 4, P &amp;lt; 0,02). The time course of this glimepiride effect on insulin-stimulated glycogen synthesis showed a peak after 12 h incubation with a half maximal effect after 4 h. Preincubation of the myotubes with wortmannin (100 nmol/l), an inhibitor of phosphatidylinositol (PI)- 3 kinase, caused an inhibition of this glimepiride effect on insulin-stimulated glycogen synthesis. In contrast to glimepiride, incubation of myotubes with glibenclamide (0–100nmol/l), a second generation sulfonylurea, had no significant effect on basal or insulin-stimulated glycogen synthesis. CONCLUSIONS—Incubation of cultured human skeletal muscle cells derived from glucose-tolerant subjects with glimepiride caused a dose-dependent increase of insulin-stimulated glycogen synthesis using therapeutic glimepiride concentrations. This glimepiride effect seems to be mediated via the PI3 kinase pathway. In contrast to glimepiride, glibenclamide had no significant effect on basal or insulin-stimulated glycogen synthesis. These results suggest that glimepiride, beside its well-known effect to stimulate insulin secretion, possess an insulin-sensitizing action in cultured human skeletal muscle cells in support of the concept of an extrapancreatic action of glimepiride.
A Statistical Evaluation of Dose Expansion Cohorts in Phase I Clinical Trials
Authors: Philip S. Boonstra, Jincheng Shen, Jeremy M.G. Taylor, Thomas M. Braun, Kent A. Griffith, Stephanie Daignault, Gregory P. Kalemkerian, Theodore S. Lawrence, Matthew J. Schipper
Journal: JNCI Journal of the National Cancer Institute (2015)

Phase I trials often include a dose expansion cohort (DEC), in which additional patients are treated at the estimated maximum tolerated dose (MTD) after dose escalation, with the goal of ensuring that data are available from more than six patients at a single dose level. However, protocols do not always detail how, or even if, the additional toxicity data will be used to reanalyze the MTD or whether observed toxicity in the DEC will warrant changing the assigned dose. A DEC strategy has not been statistically justified. We conducted a simulation study of two phase I designs: the "3+3" and the Continual Reassessment Method (CRM). We quantified how many patients are assigned the true MTD using a 10 to 20 patient DEC and how a sensible reanalysis using the DEC changes the probability of selecting the true MTD. We compared these results with those from an equivalently sized larger CRM that does not include a DEC. With either the 3+3 or CRM, reanalysis with the DEC increased the probability of identifying the true MTD. However, a large CRM without a DEC was more likely to identify the true MTD while still treating 10 or 15 patients at this dose level. Where feasible, a CRM design with no explicit DEC is preferred to designs that fix a dose for all patients in a DEC.
When the Sphingosine Kinase 1/Sphingosine 1-Phosphate Pathway Meets Hypoxia Signaling: New Targets for Cancer Therapy
Authors: Isabelle Ader, Bernard Malavaud, Olivier Cuvillier
Journal: Cancer Research (2009)

The reduction in the normal level of tissue oxygen tension or hypoxia is a characteristic of solid tumors that triggers the activation of signaling pathways promoting neovascularization, metastasis, increased tumor growth, and resistance to treatments. The activation of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) has been identified as the master mechanism of adaptation to hypoxia. In a recent study, we identified the sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) pathway, which elicits various cellular processes including cell proliferation, cell survival, or angiogenesis, as a new modulator of HIF-1alpha activity under hypoxic conditions. Here, we consider how the SphK1/S1P signaling pathway could represent a very important target for therapeutic intervention in cancer.