tbuckley/cabot-search huggingface dataset:
Induction of cytokine expression by leukemia inhibitory factor.
Authors: P M Villiger, Y Geng, M Lotz
Journal: Journal of Clinical Investigation (1993)

Biological effects of cytokines are in part determined by their interactions in the regulation of cytokine production. This study analyzes the effects of leukemia inhibitory factor (LIF) on cytokine expression in different cell lineages. Recombinant human LIF increases levels of IL-1 beta, IL-6, and IL-8 mRNA in human articular chondrocytes as demonstrated by Northern blotting. These cytokine mRNAs are detectable as early as 1.3 h after stimulation and reach their maximum after 5 h. The LIF effects are dose dependent and of similar magnitude to those of IL-1. By metabolic labeling and immunoprecipitation it is shown that LIF induces synthesis and secretion of IL-6. IL-6 bioactivity in conditioned media, as measured by the B9 hybridoma proliferation assay, is increased by LIF. Effects of LIF on cytokine expression are not confined to connective tissue cells. By PCR it is shown that human blood monocytes express IL-6 mRNA after stimulation with LIF. An increase in IL-6 mRNA levels is detectable 2 h after stimulation, and this starts to decline by 5 h. The response is of shorter duration as compared with IL-1 beta. In addition to increased mRNA expression, LIF also stimulates release of biologically active IL-6 from blood monocytes. In synoviocytes and neuronal as well as epithelial cell lines, LIF increases IL-1 beta and IL-6 gene expression. In summary, LIF induces cytokine expression in a wide variety of tissues. These results suggest that through the induction of cytokines, LIF can modulate inflammation, immune responses, and connective tissue metabolism, and act as a pathogenetic mediator in different disease states.
Neurodevelopmental and Growth Impairment Among Extremely Low-Birth-Weight Infants With Neonatal Infection
Authors: Barbara J. Stoll
Journal: JAMA (2004)

Neonatal infections are frequent complications of extremely low-birth-weight (ELBW) infants receiving intensive care. To determine if neonatal infections in ELBW infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood. Infants weighing 401 to 1000 g at birth (born in 1993-2001) were enrolled in a prospectively collected very low-birth-weight registry at academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth outcomes were assessed at a comprehensive follow-up visit at 18 to 22 months of corrected gestational age and compared by infection group. Eighty percent of survivors completed the follow-up visit and 6093 infants were studied. Registry data were used to classify infants by type of infection: uninfected (n = 2161), clinical infection alone (n = 1538), sepsis (n = 1922), sepsis and necrotizing enterocolitis (n = 279), or meningitis with or without sepsis (n = 193). Cognitive and neuromotor development, neurologic status, vision and hearing, and growth (weight, length, and head circumference) were assessed at follow-up. The majority of ELBW survivors (65%) had at least 1 infection during their hospitalization after birth. Compared with uninfected infants, those in each of the 4 infection groups were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy (range of significant odds ratios [ORs], 1.4-1.7), low Bayley Scales of Infant Development II scores on the mental development index (ORs, 1.3-1.6) and psychomotor development index (ORs, 1.5-2.4), and vision impairment (ORs, 1.3-2.2). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome. This large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood. Additional studies are needed to elucidate the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored.
The isolated sinoatrial node cell in primary culture from the newborn rat.
Authors: W J Marvin, V L Chittick, J K Rosenthal, A Sandra, D L Atkins, K Hermsmeyer
Journal: Circulation Research (1984)

We prepared primary cell cultures of the sinus node region from newborn rat hearts. Sinoatrial node cells were easily distinguished from the other cardiac muscle cells and nonmuscle cells in culture by size, configuration, and rapid, attenuated spontaneous contractions (185.0 +/- 8/min, mean +/- SEM). The spontaneously contracting sinoatrial node cells were extremely sensitive to acetylcholine and norepinephrine, responding to concentrations at least 1000-fold less than other cardiac muscle cells. These same sinoatrial node cells in culture were fixed and precisely relocated by either subsequent scanning or transmission electron microscopy. The ultrastructural features of these sinoatrial node cells in culture were similar to those observed in the cells of intact sinus node sections from the source hearts. This study is the first to present single, spontaneously active, neonatal sinoatrial node cells maintained in vitro with morphological and functional properties desirable for physiological investigations.
Disease Management Advice Provided to African-American and Chinese-American Patients With Type 2 Diabetes
Authors: Lawrence Fisher, Marilyn M. Skaff, Catherine A. Chesla, Kevin M. Chun, Joseph T. Mullan, Richard A. Kanter, Phillip S. Gardiner
Journal: Diabetes Care (2004)

Patients from diverse communities with diabetes have poorer glycemic control (1) and more complications (2) than other patients with diabetes. Ethnicity alone, however, is insufficient to account for these differences because considerable within-group variation also occurs (3). To gain a better understanding of factors that contribute to this variation, we asked African-American and Chinese-American patients with type 2 diabetes what they had been advised to do to manage their disease by their diabetes practitioners and linked their responses to their reports of actual behavior. We also investigated what factors accounted for differences in reported advice received among members of each community. Understanding these issues highlights deficits in informational exchange for these populations and identifies characteristics of minority patients that place them at risk of not obtaining specific kinds of disease-management information.

As part of a larger study (3,4), patients who met the following inclusion criteria were identified from 10 community health care settings: a diagnosis of type 2 diabetes for at least 1 year, age between 25 and 70 years, no evidence of major diabetes complications, living in the U.S. for a minimum of 1 year, and self-identified as Chinese American (born in the U.S. or Asia) or African American (born in the U.S.).

Screening identified 412 eligible Chinese-American patients, and 194 agreed to participate (47%). This modest acceptance rate is consistent with past reports on the many challenges of obtaining a high response rate among Asian Americans (11). Screening identified 300 eligible African-American patients, and 205 agreed to participate (68%). Complete …
Oral tolerance: is it all retinoic acid?
Authors: Harald von Boehmer
Journal: The Journal of Experimental Medicine (2007)

Oral tolerance has been argued to depend on “special” presentation of antigen in the gut. New studies support this idea by showing that the catalysis of vitamin A into retinoic acid (RA) in gut-associated dendritic cells (DCs) enhances the transforming growth factor (TGF)-β–dependent conversion of naive T cells into regulatory T (T reg) cells and also directs T reg cell homing to the gut. These results reveal new tolerance mechanisms that will aid the use of T reg cells in the clinic.
Prion protein lacks robust cytoprotective activity in cultured cells
Authors: Heather M Christensen, David A Harris
Journal: Molecular Neurodegeneration (2008)

The physiological function of the cellular prion protein (PrPC) remains unknown. However, PrPC has been reported to possess a cytoprotective activity that prevents death of neurons and other cells after a toxic stimulus. To explore this effect further, we attempted to reproduce several of the assays in which a protective activity of PrP had been previously demonstrated in mammalian cells. In the first set of experiments, we found that PrP over-expression had a minimal effect on the death of MCF-7 breast carcinoma cells treated with TNF-α and Prn-p 0/0 immortalized hippocampal neurons (HpL3-4 cells) subjected to serum deprivation. In the second set of assays, we observed only a small difference in viability between cerebellar granule neurons cultured from PrP-null and control mice in response to activation of endogenous or exogenous Bax. Taken together, our results suggest either that cytoprotection is not a physiologically relevant activity of PrPC, or that PrPC-dependent protective pathways operative in vivo are not adequately modeled by these cell culture systems. We suggest that cell systems capable of mimicking the neurotoxic effects produced in transgenic mice by N-terminally deleted forms of PrP or Doppel may represent more useful tools for analyzing the cytoprotective function of PrPC.
VariantDB: a flexible annotation and filtering portal for next generation sequencing data
Authors: Geert Vandeweyer, Lut Van Laer, Bart Loeys, Tim Van den Bulcke, R Frank Kooy
Journal: Genome Medicine (2014)

Interpretation of the multitude of variants obtained from next generation sequencing (NGS) is labor intensive and complex. Web-based interfaces such as Galaxy streamline the generation of variant lists but lack flexibility in the downstream annotation and filtering that are necessary to identify causative variants in medical genomics. To this end, we built VariantDB, a web-based interactive annotation and filtering platform that automatically annotates variants with allele frequencies, functional impact, pathogenicity predictions and pathway information. VariantDB allows filtering by all annotations, under dominant, recessive or de novo inheritance models and is freely available at http://www.biomina.be/app/variantdb/.
Natural family planning. Advocates and detractors have different sexual philosophies.
Authors: J Lee
Journal: BMJ (1993)

There is agreement in the correspondence on R. E. J. Ryders review of natural family planning (NFP) at least among the letters by those who are able to be objective that the method works among motivated people who can abstain from sexual intercourse during the fertile phase impossible or unnatural though this may seem to many. What comes through vividly however is the chasm that exists between the primal sexual philosophy that Ryders detractors represent and the more sublime ideals that aficionados of NFP champion. The sexual sensitivities of the two camps differ greatly. This is highlighted by the term periodic  with its emphasis on the loss of intercourse--a description of NFP that its practitioners never use. N. Hampton and D. Mansour refer to baboons and chimpanzees as role models for human sexual behavior. They argue that artificial feeding and artificial contraception are morally symmetrical and should both be condemned or both be endorsed. As it is commonly accepted that artificial feeding is inferior to breast feeding they should have no difficulty denouncing artificial contraception. There is no doubt and on this both sides concur that monkeys cannot use NFP. NFP is alien to those for whom abstinence is a forgotten experience. Couples who use NFP are committed to sexual discipline in a value system that has its origins and its aspirations in God; they choose to live by their fertility rather than to override it. Incidentally neither St. Augustine nor his putative belief that sexual intercourse is good only for procreation is mentioned in Humanae Vitae. Instead this document contains the unequivocal statement that the sexual act has both unitive and procreative meanings and indicates that the Catholic church considers recourse to the infecund periods to be licit. This shows that the church accepts that sexual intercourse has to do not only with procreation but also with the deepening of love. (full text)
Prophylaxis Strategies for Contrast-Induced Nephropathy
Authors: Neesh Pannu, Natasha Wiebe, Marcello Tonelli, for the Alberta Kidney Disease Network
Journal: JAMA (2006)

Context Contrast-induced nephropathy is associated with significant economic and clinical consequences, including prolonged hospitalization, the requirement for dialysis, and an increased risk of death.Objectives To summarize the current state of evidence for prophylaxis of contrastinduced nephropathy, provide evidence-based recommendations regarding management of high-risk patients undergoing angiographic procedures, and identify new avenues for research.Data Sources Systematic searches of peer-reviewed publications were performed in MEDLINE, EMBASE, and the Cochrane database from 1966 to January 2006.Search terms included radio contrast nephropathy, contrast media, acetylcysteine, theophylline, sodium bicarbonate, HMG Co-A reductase inhibitors, ascorbic acid, kidney diseases, renal insufficiency, kidney failure, nephropathy, fenoldopam, diuretics, and saline or half saline.Study Selection Observational studies of risk factors and randomized controlled trials of prophylaxis strategies for contrast-induced nephropathy that specified a definition of contrast-induced nephropathy or postprocedure creatinine level as an outcome measure.Evidence Synthesis Important patient-related risk factors for contrast-induced nephropathy include chronic kidney disease, diabetes mellitus, heart failure, older age, anemia, and left ventricular systolic dysfunction.Non-patient-related risk factors include highosmolar contrast, ionic contrast, contrast viscosity, and contrast volume.Practice guidelines recommend obtaining preprocedural serum creatinine levels among patients with renal disease, diabetes, proteinuria, hypertension, gout, or congestive heart failure.Available evidence, largely based on small-to medium-sized trials, supports the use of hydration, bicarbonate, and low volumes of iso-or low-osmolar contrast in patients at risk.N-acetylcysteine or ascorbic acid may be of value in very high-risk patients.Conclusions While several risk factors for contrast-induced nephropathy have been identified, the development of an effective prophylaxis strategy for contrast-induced nephropathy has been limited by our poor understanding of the pathophysiology and the clinical significance of this condition.Future research should focus on correctly identifying higher-risk patients and testing therapies in the setting of large well-powered clinical trials.
Disruption of Follicular Dendritic Cells–Follicular Lymphoma Cross-talk by the Pan-PI3K Inhibitor BKM120 (Buparlisib)
Authors: Alba Matas-Céspedes, Vanina Rodriguez, Susana G. Kalko, Anna Vidal-Crespo, Laia Rosich, Teresa Casserras, Patricia Balsas, Neus Villamor, Eva Giné, Elías Campo, Gaël Roué, Armando López-Guillermo, Dolors Colomer, Patricia Pérez-Galán
Journal: Clinical Cancer Research (2014)

Abstract Purpose: To uncover the signaling pathways underlying follicular lymphoma–follicular dendritic cells (FL–FDC) cross-talk and its validation as new targets for therapy. Experimental Design: FL primary cells and cell lines were cocultured in the presence or absence of FDC. After 24 and 48 hours, RNA was isolated from FL cells and subjected to gene expression profiling (GEP) and data meta-analysis using DAVID and GSEA softwares. Blockade of PI3K pathway by the pan-PI3K inhibitor BKM120 (buparlisib; Novartis Pharmaceutical Corporation) and the effect of PI3K inhibition on FL–FDC cross-talk were analyzed by means of ELISA, RT-PCR, human umbilical vein endothelial cell tube formation, adhesion and migration assays, Western blot, and in vivo studies in mouse FL xenografts. Results: GEP of FL–FDC cocultures yields a marked modulation of FL transcriptome by FDC. Pathway assignment by DAVID and GSEA software uncovered an overrepresentation of genes related to angiogenesis, cell adhesion, migration, and serum-response factors. We demonstrate that the addition of the pan-PI3K inhibitor BKM120 to the cocultures was able to downregulate the expression and secretion of proangiogenic factors derived from FL–FDC cocultures, reducing in vitro and in vivo angiogenesis. Moreover, BKM120 efficiently counteracts FDC-mediated cell adhesion and impedes signaling and migration induced by the chemokine CXCL12. BKM120 inhibits both constitutive PI3K/AKT pathway and FDC- or CXCL12-induced PI3K/AKT pathway, hampers FDC survival signaling, and reduces cell proliferation of FL cells in vitro and in mouse xenografts. Conclusions: These data support the use of BKM120 in FL therapy to counteract microenvironment-related survival signaling in FL cells. Clin Cancer Res; 20(13); 3458–71. ©2014 AACR.
Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain.
Authors: P Hwu, G E Shafer, J Treisman, D G Schindler, G Gross, R Cowherd, S A Rosenberg, Z Eshhar
Journal: The Journal of Experimental Medicine (1993)

To expand the spectrum of recognition of effector lymphocytes and to redirect them towards predefined targets, we have altered the specificity of human tumor-infiltrating lymphocytes (TIL) through stable modification with chimeric receptor genes consisting of single-chain antibody variable regions linked to the gamma subunit common to the immunoglobulin (Ig)G and IgE Fc receptors. Using either hapten or ovarian carcinoma-specific monoclonal antibodies, we constructed chimeric receptor genes and retrovirally introduced them into CD8+ TIL. Redirected TIL specifically lysed trinitrophenyl-labeled Daudi or a human ovarian carcinoma cell line (IGROV-1), and secreted granulocyte/macrophage colony-stimulating factor upon stimulation with the appropriate antigen. This strategy may allow new approaches towards the adoptive immunotherapy of cancer in humans.
Transient responses of rabbit cerebral blood vessels to norepinephrine: correlation with intrinsic myogenic tone.
Authors: J A Bevan
Journal: Circulation Research (1979)

Transient contractile responses to norepinephrine (NE) of vascular segments from the rabbit vertebral, internal carotid, and basilar arteries rise to a peak within several seconds, and in the presence of the agonist, reverse rapidly, relaxing with a half-time of 15 +/- 3.2 seconds. In the basilar artery, peak contraction is approximately 25% of the maximum response mediated via the "alpha-like" adrenoreceptors and is elicited by NE 10(-7) M. Steady state contractions are seen with higher concentrations. Transient contractile responses are absent in segments from the brachiocephalic and external carotid arteries, and their incidence increases the more rostral along the length of the vertebral and internal carotid artery the origin of the segment studied. They were seen in all preparations of the intracranial vertebral and basilar arteries. There is a good correlation between the occurrence in any particular vascular segment of the transient contractile response and intrinsic tone as assessed by relaxation to papaverine (10(-6) M). The response was blocked by alpha-adrenergic receptor blocking agents and was not elicited by d-NE nor tetrahydrazoline or oxymetazoline. This response may be analogous to the first phase of the biphasic contraction found in many other blood vessels. Since in cerebral vessels the agonist concentration to elicit the first phase is several orders of magnitude lower than the second, it can appear in the absence of the latter.
Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma
Authors: Mario Castro, Michael E. Wechsler, Gerard Cox
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle.Objectives: To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting β2-agonists.Methods: A total of 288 adult subjects (Intent-to-Treat [ITT]) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%).Measurements and Main Results: The improvement from baseline in the integrated AQLQ score was...
Gelatin Hydrogel Microspheres Enable Pinpoint Delivery of Basic Fibroblast Growth Factor for the Development of Functional Collateral Vessels
Authors: Akihiro Hosaka, Hiroyuki Koyama, Toshihiro Kushibiki, Yasuhiko Tabata, Nobuhiro Nishiyama, Tetsuro Miyata, Hiroshi Shigematsu, Tsuyoshi Takato, Hirokazu Nagawa
Journal: Circulation (2004)

Various growth factors promote collateral vessel development and are regarded as promising for the treatment of vascular occlusive diseases. However, an efficacious delivery system for them has yet to be established. We devised a strategy to augment functional collateral vessels by using acidic gelatin hydrogel microspheres (AGHMs) incorporating basic fibroblast growth factor (bFGF). The aim of the present study was to investigate the hypothesis that by intra-arterial (IA) administration of bFGF-impregnated AGHMs, bFGF could be delivered from AGHMs trapped in distal small-diameter vessels and thereby induce functional collateral vessels with an assured blood supply through the process of arteriogenesis.Various sizes of AGHMs (3 mg) incorporating 125I-labeled bFGF were injected into the left internal iliac artery of a rabbit model of hindlimb ischemia. Less than 50% of radioactivity accumulated in the ischemic hindlimb after injection of AGHMs that were 10 mum in diameter, whereas approximately 80% of radioactivity was counted in the ischemic limb after administration of 29- or 59-microm-diameter AGHMs. Calf blood pressure ratio and the ratio of regional blood flow of the bilateral hindlimbs immediately before and after IA administration of 29-microm-diameter AGHMs showed no significant change. Then we evaluated the function of the developed collateral vessels 28 days after IA administration of bFGF-impregnated, 29-microm-diameter AGHMs. IA administration of bFGF-impregnated AGHMs induced marked collateral vessel improvement compared with IA administration of phosphate buffered saline-treated AGHMs and intramuscular administration of bFGF-impregnated AGHMs.IA administration of bFGF-impregnated, 29-microm-diameter AGHMs strongly induced functional collateral vessels without worsening ischemia, indicating the possible therapeutic usefulness of this approach.