tbuckley/cabot-search huggingface dataset:
Kinetics of Eotaxin Generation and Its Relationship to Eosinophil Accumulation in Allergic Airways Disease: Analysis in a Guinea Pig Model In Vivo
Authors: Alison A. Humbles, Dolores M. Conroy, Sylvie Marleau, Sara M. Rankin, Roger T. Palframan, Amanda E.I. Proudfoot, Timothy N.C. Wells, Dechun Li, Peter K. Jeffery, David A. Griffiths-Johnson, Timothy J. Williams, Peter J. Jose
Journal: The Journal of Experimental Medicine (1997)

Challenge of the airways of sensitized guinea pigs with aerosolized ovalbumin resulted in an early phase of microvascular protein leakage and a delayed phase of eosinophil accumulation in the airway lumen, as measured using bronchoalveolar lavage (BAL). Immunoreactive eotaxin levels rose in airway tissue and BAL fluid to a peak at 6 h falling to low levels by 12 h. Eosinophil numbers in the tissue correlated with eotaxin levels until 6 h but eosinophils persisted until the last measurement time point at 24 h. In contrast, few eosinophils appeared in BAL over the first 12 h, major trafficking through the airway epithelium occurring at 12–24 h when eotaxin levels were low. Constitutive eotaxin was present in BAL fluid. Both constitutive and allergen-induced eosinophil chemoattractant activity in BAL fluid was neutralized by an antibody to eotaxin. Allergen-induced eotaxin appeared to be mainly in airway epithelium and macrophages, as detected by immunostaining. Allergen challenge of the lung resulted in a rapid release of bone marrow eosinophils into the blood. An antibody to IL-5 suppressed bone marrow eosinophil release and lung eosinophilia, without affecting lung eotaxin levels. Thus, IL-5 and eotaxin appear to cooperate in mediating a rapid transfer of eosinophils from the bone marrow to the lung in response to allergen challenge.
Posing the Question Again
Authors: Orson W. Moe
Journal: Journal of the American Society of Nephrology (2009)

The question of whether hyperuricemia can induce chronic direct renal injury has been argued for many decades. Despite continued efforts and strong motivations to seek an answer, the current evidence still cannot definitively prove or refute the hypothesis. Recent data in rodents do favor causality between hyperuricemia and renal disease. Human epidemiologic data are quite varied, but positive studies do exist. Pathophysiologic models of biology for this entity are sparse in animals and nonexistent in humans.
Modulation of host inflammatory mediators as a treatment strategy for periodontal diseases
Authors: DAVID W. PAQUETTE, RAY C. WILLIAMS
Journal: Periodontology 2000 (2000)

Studies ranging from preclinical animal models to human clinical trials support the basic hypothesis that the inhibition of local arachidonic acid metabolites with nonsteroidal anti-inflammatory drugs slows periodontal disease progression. Data on modulation of other host mediators such as cytokines and NO remain restricted to laboratory or preclinical investigations, but appear promising. It is unlikely that such agents, following regulatory approval, will be used ubiquitously in patient populations, but rather may be targeted for at-risk patients. In the emerging field of periodontal medicine, patient cohorts are currently being identified with genetically based inflammatory mediator hyper-responses (48, 49, 68, 115). Such cohorts who respond to the endotoxin challenge posed by periodontitis with a robust release of cytokines or prostaglandins may benefit most in terms of slowing periodontitis progression and potentially improving systemic susceptibility (3, 67).
Low density lipoproteins transfer bacterial lipopolysaccharides across endothelial monolayers in a biologically active form.
Authors: M Navab, G P Hough, B J Van Lenten, J A Berliner, A M Fogelman
Journal: Journal of Clinical Investigation (1988)

Rabbit aortic endothelial cells (RAECs) were grown on micropore filters in a device that allowed in situ determination of transendothelial electrical resistance (TEER). Incubation of confluent RAEC monolayers with 2 ng.ml-1 of bacterial LPS for 3 h did not change the protein content or the number of cells on the filters, but resulted in a marked decline in TEER (from 14.1 +/- 0.9 to 5.1 +/- 0.6 omega.cm2) and a significant increase in LDL transport across the monolayers (from 154 +/- 13 to 456 +/- 41 ng. h-1 per cm2). In contrast, exposure of RAEC monolayers for 3 d to as much as 5 micrograms.ml-1 of LPS complexed to LDL (LPS-LDL) did not alter the TEER or LDL transport. LPS-LDL was transported across the monolayers at the same rate as LDL. While microgram quantities of LPS complexed to LDL did not disrupt the integrity of the endothelial monolayer, incubation of RAECs with transported LPS-LDL at concentrations of 25-100 ng LPS.ml-1 resulted in a two- to ninefold increase in the secretion of monocyte chemotactic activity by these cells. Incubation of rabbit aortic smooth muscle cells with transported LPS-LDL at concentrations of 25-100 ng LPS.ml-1 resulted in a two- to threefold increase in the secretion of monocyte chemotactic activity. We propose that LDL protects endothelial cells from the acute toxicity of LPS but the resulting complexes are transported across the endothelium in a biologically active form that can initiate an inflammatory response.
Intralesional triamcinolone acetonide using the Port-O-Jet and needle injections in localized dermatoses
Authors: J.J. BLEEKER
Journal: British Journal of Dermatology (1974)

Journal Article Intralesional triamcinolone acetonide using the Port‐O‐Jet and needle injections in localized dermatoses Get access J.J. BLEEKER J.J. BLEEKER Dermatology Departments, General Hospitals, Lidkoping and Skovde, Sweden *Reprint requests to: Dr J. J. Bleeker, Linjevagen 11, S‐531 00, Lidkoping, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue 1, 1 July 1974, Pages 97–101, https://doi.org/10.1111/j.1365-2133.1974.tb06724.x Published: 01 July 1974 Article history Accepted: 18 September 1973 Published: 01 July 1974
Diminished endothelium-derived relaxing factor activity in an experimental model of chronic heart failure.
Authors: M Ontkean, R Gay, B Greenberg
Journal: Circulation Research (1991)

Abnormalities in vasomotor tone, including enhanced vasoconstriction at rest and diminished vasodilation in response to various stimuli, develop as a consequence of chronic heart failure. This study was undertaken to evaluate whether a specific local mechanism, namely endothelium-derived relaxing factor (EDRF) activity, might be impaired in an experimental model of chronic heart failure. Segments of thoracic aorta (TA) and pulmonary artery (PA) were isolated from a group of rats that had hemodynamic evidence of heart failure 10 weeks after ligation of the left coronary artery (n = 25) and from a group of sham-operated control rats (n = 18). Both endothelium-dependent and endothelium-independent vascular responses were assessed by exposing arterial segments to increasing concentrations of agonists. All studies were performed in the presence of 10 microM indomethacin to avoid the influence of vasoactive prostanoids. The dose-response curve for EDRF-mediated relaxation to acetylcholine was shifted rightward in rats with heart failure, and the concentrations of acetylcholine required to achieve 50% maximal relaxation (EC50) were increased compared with those of control rats in both TA and PA segments. Additionally, the dose-response curve for relaxation to ADP was shifted rightward with significantly increased EC50 in PA segments from rats with heart failure. In contrast, EDRF-mediated relaxation to the calcium ionophore A23187 was similar in the groups. Endothelium-independent relaxation to nitroglycerin was slightly increased in TA but not PA segments in the heart-failure group. Basal EDRF activity, as assessed by the increase in force after exposure to hemoglobin, was diminished in PA segments from rats with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
A Phase I Pharmacokinetic and Pharmacodynamic Study of OGX-011, a 2′-Methoxyethyl Antisense Oligonucleotide to Clusterin, in Patients With Localized Prostate Cancer
Authors: Kim N. Chi, Elizabeth Eisenhauer, Ladan Fazli, Edward C. Jones, S. Larry Goldenberg, Jean Powers, Dongsheng Tu, Martin E. Gleave
Journal: JNCI Journal of the National Cancer Institute (2005)

Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 is a 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA and has been reported to inhibit clusterin expression and enhance drug efficacy in xenograft models. The primary objective of this clinical study was to determine a biologically effective dose of OGX-011 that would inhibit clusterin expression in human cancer.Subjects (n = 25) with localized prostate cancer with high-risk features who were candidates for prostatectomy were treated with OGX-011 by 2-hour intravenous infusion on days 1, 3, and 5 and then weekly from days 8-29 combined with androgen blockade starting on day 1; prostatectomy was performed on days 30-36. Six different doses were tested, from 40 to 640 mg. OGX-011 plasma and prostate tissue concentrations were measured by an enzyme-linked immunosorbent assay method, and the pharmacokinetics of OGX-011 were determined from these data. Prostate cancer tissue, lymph nodes, and serial samples of peripheral blood mononuclear cells were assessed for clusterin expression using quantitative real-time polymerase chain reaction and immunohistochemistry. All statistical tests were two-sided.Only grade 1 and 2 toxicities were observed. The plasma half-life of OGX-011 was approximately 2-3 hours, and the area under the concentration versus time curve and CMAX (peak plasma concentration) increased proportionally with dose (Ptrend < .001). OGX-011 in prostate tissue increased with dose (Ptrend < .001). Dose-dependent decreases in prostate cancer and lymph node clusterin expression were observed by polymerase chain reaction of greater than 90% (Ptrend = .008 and Ptrend < .001, respectively) and by immunohistochemistry (Ptrend < .001 and Ptrend = .01, respectively).OGX-011 is well tolerated and reduces clusterin expression in primary prostate tumors. The optimal biologic dose for OGX-011 at the schedule used is 640 mg.
Effect of Diabetes and Associated Conditions on Long-Term Survival After Coronary Artery Bypass Graft Surgery
Authors: Bruce J. Leavitt, Lynne Sheppard, Christopher Maloney, Robert A. Clough, John H. Braxton, David C. Charlesworth, Ronald M. Weintraub, Felix Hernandez, Elaine M. Olmstead, William C. Nugent, Gerald T. O’Connor, Cathy S. Ross
Journal: Circulation (2004)

Background— The effects of diabetes on short-term results of coronary artery bypass graft (CABG) surgery are known, but less is known about the long-term effects of diabetes and diabetic-related sequelae for patients undergoing this surgery. We studied the 10-year survival of nondiabetic and diabetic patients undergoing CABG surgery. Methods and Results— A prospective regional cohort study was conducted of 36 641 consecutive isolated CABG patients in northern New England from 1992 through 2001. Patient records were linked to the National Death Index to assess mortality. There were 154 140 person-years of follow-up and 5779 deaths. Kaplan–Meier techniques were used. Survival was stratified into three categories: no diabetes, diabetes without peripheral vascular disease and renal failure, and diabetes with peripheral vascular disease and/or renal failure. The overall annual incidence rate of death was 3.7 deaths per 100 person-years. Annual incidence rates for nondiabetic subjects and diabetic subjects were similar: 3.1 deaths per 100 person-years and 4.4 deaths per 100 person-years, respectively. The annual incidence rate for diabetic subjects with renal failure, peripheral vascular disease, or both was 9.4 deaths per 100 person-years. The log-rank test showed that the survival curves were significantly different ( P &lt;0.001). Conclusion— Patients that have diabetes without the sequelae of renal failure and/or peripheral vascular disease have long-term survival similar to but slightly less than patients without diabetes who undergo CABG surgery. Survival of CABG surgery patients with diabetes is greatly affected by associated comorbidities of peripheral vascular disease and renal failure. This knowledge may help guide the patient as well as the cardiologist and cardiac surgeon in making appropriate decisions in these critically ill patients.
ST-Segment Elevation Myocardial Infarction in Women With Type 2 Diabetes
Authors: Edyta Radomska, Marcin Sadowski, Jacek Kurzawski, Marek Gierlotka, Lech Poloński
Journal: Diabetes Care (2013)

To evaluate the effect of type 2 diabetes on the clinical course and prognosis of women with ST-segment elevation myocardial infarction (STEMI) and diabetes.
<i>MYC</i> Amplification and Polysomy 8 in Chondrosarcoma: Array Comparative Genomic Hybridization, Fluorescent In Situ Hybridization, and Association With Outcome
Authors: Carl Morrison, Michael Radmacher, Nehad Mohammed, David Suster, Herbert Auer, Susie Jones, Judy Riggenbach, Nicole Kelbick, Gary Bos, Joel Mayerson
Journal: Journal of Clinical Oncology (2005)

To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion.Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation.Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance.MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.
Molecular pathogenesis and clinical management of Fanconi anemia
Authors: Younghoon Kee, Alan D. D’Andrea
Journal: Journal of Clinical Investigation (2012)

Fanconi anemia (FA) is a rare genetic disorder associated with a high frequency of hematological abnormalities and congenital anomalies. Based on multilateral efforts from basic scientists and clinicians, significant advances in our knowledge of FA have been made in recent years. Here we review the clinical features, the diagnostic criteria, and the current and future therapies of FA and describe the current understanding of the molecular basis of the disease.
The Role of Inflammatory Cytokines in Diabetic Nephropathy
Authors: Juan F. Navarro-González, Carmen Mora-Fernández
Journal: Journal of the American Society of Nephrology (2008)

Cytokines act as pleiotropic polypeptides regulating inflammatory and immune responses through actions on cells. They provide important signals in the pathophysiology of a range of diseases, including diabetes mellitus. Chronic low-grade inflammation and activation of the innate immune system are closely involved in the pathogenesis of diabetes and its microvascular complications. Inflammatory cytokines, mainly IL-1, IL-6, and IL-18, as well as TNF-alpha, are involved in the development and progression of diabetic nephropathy. In this context, cytokine genetics is of special interest to combinatorial polymorphisms among cytokine genes, their functional variations, and general susceptibility to diabetic nephropathy. Finally, the recognition of these molecules as significant pathogenic mediators in diabetic nephropathy leaves open the possibility of new potential therapeutic targets.
Neurodevelopment of Children Following Prenatal Exposure to Venlafaxine, Selective Serotonin Reuptake Inhibitors, or Untreated Maternal Depression
Authors: Irena Nulman, Gideon Koren, Joanne Rovet, Maru Barrera, Ariel Pulver, David Streiner, Brian Feldman
Journal: American Journal of Psychiatry (2012)

Effects on child neurodevelopment of neurotransmitter reuptake inhibitors used as antidepressants during pregnancy have not been adequately studied. The authors compared the effects of prenatal exposure to venlafaxine (serotonin-norepinephrine reuptake inhibitor), selective serotonin reuptake inhibitors (SSRIs), and maternal depression.A cohort derived from a prospectively collected database included four groups of children born to 1) depressed women who took venlafaxine during pregnancy (N=62), 2) depressed women who took SSRIs during pregnancy (N=62), 3) depressed women who were untreated during pregnancy (N=54), and 4) nondepressed, healthy women (N=62). The children's intelligence and behavior outcomes were evaluated with standardized instruments at one time point between the ages of 3 years and 6 years, 11 months.The children exposed to venlafaxine, SSRIs, and maternal depression during pregnancy had similar full-scale IQs (105, 105, and 108, respectively). The IQs of the venlafaxine and SSRI groups were significantly lower than that of the children of nondepressed mothers (112). The three groups exposed to maternal depression had consistently, but nonsignificantly, higher rates of most problematic behaviors than the children of nondepressed mothers. Severity of maternal depression in pregnancy and at testing predicted child behavior. Maternal IQ and child sex predicted child IQ. Antidepressant dose and duration during pregnancy did not predict any cognitive or behavioral outcome.Factors other than antidepressant exposure during pregnancy strongly predict children's intellect and behavior. Depression during pregnancy is a significant risk factor for postpartum depression. Children of depressed mothers may be at risk of future psychopathology.
Empirical Evaluation of Gene and Environment Interactions: Methods and Potential
Authors: R. L. Prentice
Journal: JNCI Journal of the National Cancer Institute (2011)

In this issue of the Journal, Campa et al. (1) empirically examine interactions between single-nucleotide polymorphisms (SNPs) that have been associated with disease incidence and certain risk factors, for breast cancer. The authors analyzed data from 8576 breast cancer case subjects and 11 892 control subjects from the Breast and Prostate Cancer Cohort Consortium (BPC3), more than 80% of whom are of European ancestry, for interactions between 17 SNPs that were “strongly and statistically significantly” associated with breast cancer risk in previous studies, and nine established breast cancer risk factors. They summarize that “this study does not support the hypothesis that known common breast cancer susceptibility loci strongly modify the association between established risk factors and cancer,” and they argue that “these findings are important given the size, prospective design, and comprehensive approach of the study.”
T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection Requires T Cell Expression of the Histone Demethylase UTX
Authors: Kevin D. Cook, Karl B. Shpargel, Joshua Starmer, Fatima Whitfield-Larry, Bridget Conley, Denise E. Allard, Julia E. Rager, Rebecca C. Fry, Marsha L. Davenport, Terry Magnuson, Jason K. Whitmire, Maureen A. Su
Journal: Immunity (2015)
Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: A double-blind RCT
Authors: J García-Pagán
Journal: Hepatology (2003)

Nonselective β-blockers are very effective in preventing first variceal bleeding in patients with cirrhosis. Treatment with isosorbide-5-mononitrate (IS-MN) plus propranolol achieves a greater reduction in portal pressure than propranolol alone. The present multicenter, prospective, double-blind, randomized, controlled trial evaluated whether combined drug therapy could be more effective than propranolol alone in preventing variceal bleeding. A total of 349 consecutive cirrhotic patients with gastroesophageal varices were randomized to receive propranolol + placebo (n = 174) or propranolol + IS-MN (n = 175). There were no significant differences in the 1- and 2-year actuarial probability of variceal bleeding between the 2 groups (propranolol + placebo, 8.3% and 10.6%; propranolol + IS-MN, 5% and 12.5%). The only independent predictor of variceal bleeding was a variceal size greater than 5 mm. However, among patients with varices greater than 5 mm (n = 196), there were no significant differences in the incidence of variceal bleeding between the 2 groups. Survival was also similar. Adverse effects were significantly more frequent in the propranolol + IS-MN group due to a greater incidence of headache. There were no significant differences in the incidence of new-onset or worsening ascites or in impairment of renal function. In conclusion, propranolol effectively prevents variceal bleeding. Adding IS-MN does not further decrease the low residual risk of bleeding in patients receiving propranolol. However, the long-term use of this combination drug therapy is safe and may be an alternative in clinical conditions associated with a greater risk of bleeding.
Report on M, Pasteur's Researches on Rabies and the Treatment of Hydrophobia by Preventive Inoculation
Authors: M. W. Vignal
Journal: BMJ (1886)

ANIMALS-A Prophylactic for Hydrophobia.-Statments of HM.Ctollier and Gibier negatited byZf.Pasteur.-Virclence of Virus Attenuated by Passage through a Scries of Monlkeys.-Virilcnec of Virus increased by Panage through a Series of Rabbits and (uinca- Pigs.Virulence of Viru brought to a Maximuma in Rabbits persits; if usd forInoculating Dogs, itproduces Fatal Babies.-Atenu-ated Virus from Monkeys regains its Maximunm Virulence aftcr Passage through a Series of Babbits.Virts of Dierest Degrees of Virlzzence obtained.-Inoculatwwith Rabid Virus described: Viru- lence of Virus gradually increases.-Jethod of Rendering Dogs Befractory to Jadness.-Possibility of Prophylactic I1noculation for Hydrophobia sugested.-Commission of Inquiry apointed by the Minister of Public Instruction: Report: Twcentty-tl-cc Dogs success- fully InoculateLd A Prophylacic against Hydrophobia.-OnMlay 19th, 1884, M1.Pas- teur 1 stated to the Academy of Sciences that he had advanced a step further in his experiments, for the purpose of rendering animals re- fractory to the virus of rabies by inoculation with an attenuated virus.