tbuckley/cabot-search huggingface dataset:
Activation and homologous desensitization of human endothelial cells by CD40 ligand, tumor necrosis factor, and interleukin 1.
Authors: K Karmann, W Min, W C Fanslow, J S Pober
Journal: The Journal of Experimental Medicine (1996)

We have reported previously that activation of human umbilical vein endothelial cells (HUVECs) through CD40, using a recombinant soluble form of trimerized CD40 ligand, leads to induction of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). Here, we compare the effects of CD40 ligand with those of tumor necrosis factor (TNF) and interleukin 1 (IL-1). All three ligands induce transient increases in E-selectin (peak 4 h) and VCAM-1 (peak 8-24 h), as well as sustained increases in ICAM-1 (plateau 24 h). Quantitatively, TNF is more potent than IL-1, which is much more potent than CD40 ligand. The same hierarchy is observed for transcriptional activation of an E-selectin promoter reporter gene construct in transiently transfected HUVECs. TNF and CD40 ligand each induced activation of the transcription factors NF-kappa B, IRF-1, and ATF-2/c-Jun, measured by electrophoretic mobility shift assays, but this response appeared quantitatively similar. All three agents transiently (peak 30 min) activated Jun NH2-terminal kinase (JNK), which has been implicated in transcription of E-selectin through its actions on ATF-2/c-Jun. Activation of JNK again showed a hierarchy of potency (TNF &amp;gt; IL-1 &amp;gt; CD40 ligand), although the time course of induction was similar for all three agents. After 44 h of pretreatment, TNF, IL-1, and CD40 ligand each display homologous desensitization for reinduction of surface expression of E-selectin. A similar pattern of homologous desensitization for reactivation of JNK was observed. We conclude that TNF, IL-1, and CD40 ligand all activate similar responses in ECs, and that homologous desensitization of JNK may explain the inability of individual cytokines to reinduce E-selectin expression.
Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort
Authors: Alvar Agusti, Lisa D. Edwards, Bartolomé Celli, William MacNee, Peter M. A. Calverley, Hana Müllerova, David A. Lomas, Emiel Wouters, Per Bakke, Steve Rennard, Courtney Crim, Bruce E. Miller, Harvey O. Coxson, Julie C. Yates, Ruth Tal-Singer, Jørgen Vestbo
Journal: European Respiratory Journal (2013)

The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifies patients with chronic obstructive pulmonary disease (COPD) into four groups (A to D). We explored the characteristics, stability and relationship to outcomes of these groups within the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) (n = 2101). Main results showed that: 1) these groups differed in several clinical, functional, imaging and biological characteristics in addition to those used for their own definition; 2) A and D groups were relatively stable over time, whereas groups B and C showed more temporal variability; 3) the risk of exacerbation over 3 years increased progressively from A to D, whereas that of hospitalisation and mortality were lowest in A, highest in D and intermediate and similar in B and C, despite the former having milder airflow limitation. The prevalence of comorbidities and persistent systemic inflammation were highest in group B. The different longitudinal behaviour of group A versus B and C versus D (each pair with similar forced expiratory volume in1 s (FEV1) values supports the 2011 GOLD proposal of assessing COPD patients by more than FEV1 only. However the assumption that symptoms do not equate to risk appears to be naïve, as groups B and C carry equally poor clinical outcomes, though for different reasons.
Seventeen‐year survival in multiple myeloma
Authors: Lisbeth A. Suyehira, H. Jeffrey Lawrence
Journal: American Journal of Hematology (1989)

Abstract We report a case of multiple myeloma surviving 17 years since diagnosis and 13 years in continuous complete remission since a relapse 4 years after initial treatment. Despite the prolonged remission, multiple lytic bone lesions have not healed.
HDGF-related protein-3 is required for anchorage-independent survival and chemoresistance in hepatocellular carcinomas
Authors: Qianyi Xiao, Kai Qu, Chenji Wang, Yahui Kong, Chao Liu, Deke Jiang, Hexige Saiyin, Fan Jia, Canrong Ni, Taoyang Chen, Yuanyuan Zhang, Pingzhao Zhang, Wenxin Qin, Qingwen Sun, Hongyang Wang, Qing Yi, Jun Liu, Haojie Huang, Long Yu
Journal: Gut (2012)

<h3>Objective</h3> Hepatoma-derived growth factor (HDGF)-related proteins (HRPs) comprise a family of six members and are characterised by a conserved HATH domain. Among the family members, HDGF was the first to be identified as a mitogenic factor and shown to play an important role in hepatocellular carcinoma pathogenesis. The aim of the present study is to examine the relevance of HDGF-related protein-3 (HRP-3), another member of the HRP family in hepatocellular carcinoma (HCC). <h3>Design</h3> HRP-3 expression in HCC tissues was measured by quantitative reverse transcriptase PCR, western blot and immunohistochemistry analysis. The biological consequences of overexpression and knockdown of HRP-3 in HCC cell lines were studied in vitro and in vivo. <h3>Results</h3> Expression of HRP-3 mRNA and protein was shown to be highly upregulated in HCC tissues. While knockdown of HRP-3 by small interference RNAs failed to affect anchorage-dependent growth of HCC cells, it inhibited anchorage-independent growth of HCC cells in vitro and xenograft tumour growth in vivo. Further, knockdown of HRP-3 was shown to sensitise HCC cells to anoikis. Moreover, HRP-3 specifically activated the extracellular-signal-regulated kinase (ERK) pathway without affecting c-Jun N-terminal kinase (JNK), p38, AKT and signal transducer and activator of transcription 3 (STAT3). Importantly, inhibition of the ERK pathway diminished HRP-3-mediated protection of HCC cells from anoikis. Finally, knockdown of HRP-3 was shown to enhance apoptosis of HCC cells induced by multiple chemotherapeutic drugs. <h3>Conclusion</h3> These findings indicate that HRP-3 plays an essential role in HCC pathogenesis and suggest that it may serve as a novel prognostic marker and molecular target for development of drugs for treatment of HCC.
Idiopathic Urgency Urinary Incontinence
Authors: Ingrid Nygaard
Journal: New England Journal of Medicine (2010)

At least weekly, a 62-year-old teacher has a strong sense of urgency to urinate, followed by leakage as she rushes to the bathroom. She sometimes leaks urine during exercise. She takes hydrochlorothiazide for mild hypertension. On physical examination, she is found to be obese and not to have abdominal masses or pelvic-organ prolapse.
Neoplastic Epidural Spinal Cord Compression
Authors: Harvey Gilbert
Journal: JAMA (1978)

TREATMENT of epidural involvement by metastatic cancer should be directed to the totality of the invariably present widespread metastatic systemic disease accompanying it. In contrast to patients with metastatic brain disease who frequently have interference with cognitive function, those with epidural compression usually experience the tragedy of remaining fully alert but totally paralyzed. Epidural metastases are particularly devastating in that a growing mass in a closed compartment with a marginal vascular supply can give rise to sudden paraplegia and permanent loss of function; over-whelming nursing problems and untold financial burden result. Patients with back pain from metastatic neoplasm are usually treated for "bone metastasis," and little consideration is paid to the nuances of the specific symptom complex. "Soft" neurological signs, such as pain or sensory changes in a dermatome (radicular) distribution, or minimal weakness may indicate cord compression. All of our efforts should be directed at detecting compression at this
Pregnancy Outcome Following In Utero Exposure to Lithium: A Prospective, Comparative, Observational Study
Authors: Orna Diav-Citrin, Svetlana Shechtman, Esther Tahover, Victoriya Finkel-Pekarsky, Judy Arnon, Debra Kennedy, Aida Erebara, Adrienne Einarson, Asher Ornoy
Journal: American Journal of Psychiatry (2014)

Lithium taken during the first trimester of pregnancy appears to increase the risk of cardiovascular anomalies in infants, although some of these anomalies resolve spontaneously. Lithium also raises the likelihood of miscarriage. On the other hand, the risk of illness recurrence is high for women who discontinue taking medication during pregnancy, and so the decision should be made on an individual basis. It is recommended that women treated with lithium during organogenesis receive fetal echocardiography and level-2 ultrasound.
Asthma symptoms in women employed in domestic cleaning: a community based study
Authors: M Medina-Ramon
Journal: Thorax (2003)

Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. The aim of this study was to assess the risk of asthma in women employed in domestic cleaning.A cross sectional study was conducted in 4521 women aged 30 to 65 years. Information on respiratory symptoms and cleaning work history was obtained using a postal questionnaire with telephone follow up. Asthma was defined as reported symptoms in the last year or current use of drugs to treat asthma. Odds ratios (OR) with 95% confidence intervals (CI) for asthma in different cleaning groups were estimated using adjusted unconditional logistic regression models.593 women (13%) were currently employed in domestic cleaning work. Asthma was more prevalent in this group than in women who had never worked in cleaning (OR 1.46 (95% CI, 1.10 to 1.92)). Former domestic cleaning work was reported by 1170 women (26%), and was strongly associated with asthma (OR 2.09 (1.70 to 2.57)). Current and former non-domestic cleaning work was not significantly associated with asthma. Consistent results were obtained for other respiratory symptoms. Twenty five per cent of the asthma cases in the study population were attributable to domestic cleaning work.Employment in domestic cleaning may induce or aggravate asthma. This study suggests that domestic cleaning work has an important public health impact, probably involving not only professional cleaners but also people undertaking cleaning tasks at home.
PATHWAYS AND STRATEGIES FOR DEVELOPING A MALARIA BLOOD-STAGE VACCINE
Authors: Michael F. Good, David C. Kaslow, Louis H. Miller
Journal: Annual Review of Immunology (1998)

In the past 10 years, our knowledge of the malaria parasite has increased enormously: identification and analysis of parasite antigens, demonstration of protection of monkeys and mice following immunization with these antigens, and better understanding of the mechanisms of immunity to malaria and the pathogenesis of disease in malaria. Powerful new adjuvants have been developed, some of which--it is hoped--will be suitable for human use. Recently, a successful human trial of a vaccine aimed at sporozoites (the stage inoculated by mosquitoes) was completed. However, it is the red blood cell stage of the parasite that causes disease, and it is against this stage--in which the parasite grows at an exponential rate--that it has proven very difficult to induce a protective immune response by vaccination. This review focuses on recent exciting developments toward a blood-stage vaccine. We analyze the major obstacles to vaccine development and outline a strategy involving public- and industry-funded research that should result in development of a vaccine.
New immunosuppressive regimens in lung transplantation
Authors: N Briffa, RE Morris
Journal: European Respiratory Journal (1997)

Survival after lung transplantation is less than 50% after 5 yrs and is limited by infection and obliterative bronchiolitis. There is, therefore, a need for new immunosuppressive regimens if we are to attempt to improve long-term survival. Several trials in lung transplantation of new immunosuppressive agents are in the planning stages. In this article, we review the experience with a new monoclonal agent (interleukin 2 (IL2) receptor antagonist) in kidney transplantation, together with the pharmacokinetic (PK) and pharmacodynamic properties and experience in transplantation in general, of the more promising of the new xenobiotic compounds (cyclosporine microemulsion, mycophenolate mofetil, tacrolimus and sirolimus). Recent novel approaches to the vexing problem of resistant lung rejection and obliterative bronchiolitis, such as the use of aerosolized cyclosporine, methotrexate, total lymphoid irradiation and phototherapy, are discussed. Finally an immunosuppressive regimen, using these new drugs in lung transplantation is suggested.
Topical calcipotriol in childhood psoriasis
Authors: Arnold P. Oranjea, Danielle Marcouxb, Åke Svenssonc, Julie Prendivilled, Bernice Krafchike, J Toolef, Donald Rosenthalg, Flora B. de Waard-van der Speka, Lars Molinh, Mads Axelseni
Journal: Journal of the American Academy of Dermatology (1997)
The protective role of endogenously synthesized nitric oxide in staphylococcal enterotoxin B-induced shock in mice.
Authors: S Florquin, Z Amraoui, C Dubois, J Decuyper, M Goldman
Journal: The Journal of Experimental Medicine (1994)

Nitric oxide (NO) synthesis during experimental endotoxemia has been shown to have both deleterious and beneficial effects. In the present study, we analyzed the in vivo production and the regulatory role of NO in the shock syndrome induced by staphylococcal enterotoxin B (SEB) in mice. First, we found that intraperitoneal administration of 100 micrograms SEB in BALB/c mice induced a massive synthesis of NO as indicated by high serum levels of nitrite (NO2-) and nitrate (NO3-) peaking 16 h after SEB injection. The inhibition of NO2- and NO3- release in mice injected with anti-tumor necrosis factor (TNF) and/or anti-interferon gamma (IFN-gamma) monoclonal antibody (mAb) before SEB challenge revealed that both cytokines were involved in SEB-induced NO overproduction. In vitro experiments indicated that NO synthase (NOS) inhibition by N-nitro-L-arginine methyl ester (L-NAME) enhanced IFN-gamma and TNF production by splenocytes in response to SEB. A similar effect was observed in vivo as treatment of mice with L-NAME resulted in increased IFN-gamma and TNF serum levels 24 h after SEB challenge, together with persistent expression of corresponding cytokine mRNA in spleen. The prolonged production of inflammatory cytokines in mice receiving L-NAME and SEB was associated with a 95% mortality rate within 96 h, whereas all mice survived injections of SEB or L-NAME alone. Both TNF and INF-gamma were responsible for the lethality induced by SEB in L-NAME-treated mice as shown by the protection provided by simultaneous administration of anti-IFN-gamma and anti-TNF mAbs. We conclude the SEB induces NO synthesis in vivo and that endogenous NO has protective effects in this model of T cell-dependent shock by downregulating IFN-gamma and TNF production.
Effect of different prokinetic agents and a novel enterokinetic agent on postoperative ileus in rats
Authors: B Y De Winter, G E Boeckxstaens, J G De Man, T G Moreels, J A J Schuurkes, T L Peeters, A G Herman, P A Pelckmans
Journal: Gut (1999)

<h3>BACKGROUND/AIM</h3> The effects of different prokinetic agents, the motilide erythromycin and the substituted benzamides metoclopramide and cisapride, were investigated in a rat model of postoperative ileus. These effects were compared with that of granisetron, a 5-hydroxytryptamine (5-HT<sub>3</sub>) receptor antagonist, and a novel enterokinetic agent, prucalopride, a 5-HT<sub>4</sub> receptor agonist. <h3>METHODS</h3> Different degrees of inhibition of gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy, or laparotomy plus mechanical stimulation of the gut. <h3>RESULTS</h3> Metoclopramide decreased the transit after laparotomy with or without mechanical stimulation, whereas cisapride increased it after all three operations. Granisetron had no effect on the transit after the three operations when given alone. Prucalopride tended to increase the transit after laparotomy with or without mechanical stimulation when given alone. However, statistical significance was only reached when prucalopride was combined with granisetron. Erythromycin, a motilin receptor agonist, did not improve postoperative ileus in the rat. <h3>CONCLUSIONS</h3> Cisapride, but not metoclopramide or erythromycin, is able to improve postoperative ileus in the rat. The results suggest that a combination of 5-HT<sub>3</sub> receptor antagonist and 5-HT<sub>4</sub> receptor agonist properties may be required to obtain a beneficial effect on surgery induced ileus in the rat. Furthermore, they indirectly indicate that stimulation of the excitatory mechanisms is not able to overcome the inhibitory influence of the neural reflex pathways activated during abdominal surgery.
The Response Evaluation Measure (REM-71): A New Instrument for the Measurement of Defenses in Adults and Adolescents
Authors: H Steiner, K B Araujo, C Koopman
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: There is widespread agreement that the concept of defense is useful, but large-scale studies with representative cohorts are lacking. Self-report measures capturing conscious derivatives of defense can facilitate such studies. The authors report the design and initial performance of a new self-report measure of specific defenses. METHOD: A 71-item questionnaire based on a developmental model of defenses was created, pilot tested, and refined. The item pool was given to two independent clinical researchers for the classification of items (concordance=98.5%). The instrument was then administered to 1,875 nonclinical subjects drawn from two suburban high schools and from a public waiting area of a local airport (1,038 female subjects; mean age=21.0 years, SD=11.9, range=13–89), who were also assessed with a simple screening measure covering demographic variables and satisfaction with life. RESULTS: The internal consistency of the questionnaire items was good. Two factors emerged from a factor analysis of the items, paralleling Vaillant's theoretical model. Most defenses made unique, significant contributions to these factors. Defenses and factors related in the expected direction with scores on life satisfaction in various domains. CONCLUSIONS: The Response Evaluation Measure is a brief, coherent, and potentially useful screening instrument for the assessment of defenses in adults and adolescents.
A Role for the RASSF1A Tumor Suppressor in the Regulation of Tubulin Polymerization and Genomic Stability
Authors: Michele D Vos, Alfredo Martinez, Candice Elam, Ashraf Dallol, Barbara J Taylor, Farida Latif, Geoffrey J Clark
Journal: Cancer Research (2004)

The high frequency with which the novel tumor suppressor RASSF1A is inactivated by promoter methylation suggests that it plays a key role in the development of many primary human tumors. Yet the mechanism of RASSF1A action remains unknown. We now show that RASSF1A associates with microtubules and that this association is essential for RASSF1A to mediate its growth inhibitory effects. Overexpression of RASSF1A promotes the formation of stable microtubules, whereas a dominant-negative fragment of RASSF1A destabilizes microtubule networks. The RASSF1 protein is expressed as two main isoforms, 1A and 1C. The smaller 1C isoform also associates with microtubules but is less effective at stabilizing them. Because RASSF1A and RASSF1C localize to the mitotic spindle, we examined their effects upon genomic instability. RASSF1A and RASSF1C block activated Ras-induced genomic instability. However, a point mutant of RASSF1C, identified in human tumors, was severely defective for stabilizing tubulin and was unable to block the genomic destabilizing effects of Ras. Thus, we identify a role for RASSF1A/C in the control of microtubule polymerization and potentially in the maintenance of genomic stability.
Incidence, Risk Factors, and Clinical Sequelae of Angiographic Peri-Stent Contrast Staining After Sirolimus-Eluting Stent Implantation
Authors: Masao Imai, Kazushige Kadota, Tsuyoshi Goto, Satoki Fujii, Hiroyuki Yamamoto, Yasushi Fuku, Shingo Hosogi, Akitoshi Hirono, Hiroyuki Tanaka, Takeshi Tada, Takeshi Morimoto, Hiroki Shiomi, Ken Kozuma, Katsumi Inoue, Nobuaki Suzuki, Takeshi Kimura, Kazuaki Mitsudo
Journal: Circulation (2011)

Background— We have noted abnormal angiographic findings—at the sites of drug-eluting stent implantation, suggesting contrast staining outside the stent struts—that do not fulfill the classic definition of coronary artery aneurysm. We propose a new term, peri-stent contrast staining (PSS), for these abnormal angiographic findings and assess their incidence, risk factors, and clinical sequelae. Methods and Results— Peri-stent contrast staining was defined as contrast staining outside the stent contour extending to ≥20% of the stent diameter. The study population consisted of 3081 lesions (1998 patients) that were treated exclusively with sirolimus-eluting stents and were evaluated by follow-up angiography within 12 months after sirolimus-eluting stent implantation in a single center. Late acquired PSS was observed in 58 lesions (1.9%) in 49 patients (2.5%). Independent risk factors of PSS included chronic total occlusion, whereas negative risk factors for PSS were left circumflex coronary artery lesion and in-stent restenosis lesion. Stent fracture was more frequently observed in lesions with PSS than in lesions without PSS (43.1% versus 5.4%, P &lt;0.0001). Excluding 269 lesions with target-lesion revascularization within 12 months, the study population for long-term follow-up consisted of 51 lesions (42 patients) with PSS and 2761 lesions (1751 patients) without PSS. Cumulative incidence of target-lesion revascularization and definite very late stent thrombosis at 3 years in the PSS group was higher than that in the non-PSS group (15.0% versus 6.5%, and 8.2% versus 0.2%, respectively). Conclusions— Peri-stent contrast staining found within 12 months after sirolimus-eluting stent implantation appeared to be associated with subsequent target-lesion revascularization and very late stent thrombosis.
Cough-Induced Cardiac Compression
Authors: J. Michael Criley
Journal: JAMA (1976)

Eight patients undergoing coronary angiography were successfully resuscitated from ventricular fibrillation (VF), and three of these patients remained conscious and alert for 24 to 39 seconds after VF by coughing every one to three seconds. The mean aortic systolic pressure induced by cough was 139.7 mm Hg (+/- 3.8) and only 60.7 mm Hg (+/- 5.1) by external cardiopulmonary resuscitation (CPR). Cough-CPR, accomplished by abrupt, forceful coughing maintains consciousness by rhythmic compression of the heart, has several advantages over external CPR in the catheterization laboratory, and may be applicable to other situations where serious rhythm disturbances are recognized before unconsciousness occurs.