tbuckley/cabot-search huggingface dataset:
Active and Passive Immunotherapy for Neurodegenerative Disorders
Authors: David L. Brody, David M. Holtzman
Journal: Annual Review of Neuroscience (2008)

Immunotherapeutic strategies to combat neurodegenerative disorders have galvanized the scientific community since the first dramatic successes in mouse models recreating aspects of Alzheimer disease (AD) were reported. However, initial human trials of active amyloid-beta (Abeta) vaccination were halted early because of a serious safety issue: meningoencephalitis in 6% of subjects. Nonetheless, some encouraging preliminary data were obtained, and rapid progress has been made toward developing alternative, possibly safer active and passive immunotherapeutic approaches for several neurodegenerative conditions. Many of these are currently in human trials for AD. Despite these advances, our understanding of the essential mechanisms underlying the effects seen in preclinical models and human subjects is still incomplete. Antibody-induced phagocytosis of pathological protein deposits, direct antibody-mediated disruption of aggregates, neutralization of toxic soluble proteins, a shift in equilibrium toward efflux of specific proteins from the brain, cell-mediated immune responses, and other mechanisms may all play roles depending on the specific immunotherapeutic scenario.
The most frequent comorbidies in COPD and their inflence on the prognosis of the disease
Authors: Jagoda Stojkovic, Dragana Stojkovic
Journal: European Respiratory Journal (2013)

Patients with all stages of obstructive pulmonary disease (COPD), especially older have increased risk of death from comorbidities more than COPD itself. We made a study to asses the most common comorbid diseases, and their prognostic role in patients with COPD. For that reason there have been evaluated 270 patients with different stages of COPD. The mean age was 67 ± 5 yesrs. Smoking history, age, sex, FEV1 and comorbid condition were collected from clinical records. Follow-up was made by the visits of patients every four months during three years. The mean value of FEV1 was 1,49 ± 0,37 L. The most common disease was hypertension (26%), coronary artery disease (11%), diabetes mellitus (4,2%), heart failure (4%), cancer (3,5%) OSA (3%), and cerebrovascular disease (1,7%). Hyperlipidemia was found in 43% of the evaluated subjects. 19 patients die during follow up.  We concluded that deaths were more associated with level of FEV1, heart failure, cancer and cerebrovascular accidents.
Single daily dose corticosteroid treatment.
Authors: A B Myles, L F Schiller, D Glass, J R Daly
Journal: Annals of the Rheumatic Diseases (1976)

Thirteen patients with rheumatoid or psoriatic arthritis who had not previously received corticosteroids were treated with prednisolone in a single-dose each morning. Insulin-hypoglycaemia tests were performed before starting steroids in each patient, and again at the conclusion of the study in twelve of the thirteen (duration of steroid treatment 8-40 m). There was no difference in the mean basal or peak levels of corticosteroids, or the mean peak of growth hormone (GH) in the tests done before or during treatment, although one patient lost GH responsiveness. There was thus no evidence of hypothalamo-pituitary-adrenal (HPA) suppression in any of the twelve patients, and there was a good therapeutic response in twelve out of thirteen. One patient was dropped from the trial because treatment failed. In contrast, of seven patients who had received a similar total dose of prednisolone twice daily, three showed HPA suppression and two had lost GH responsiveness.
Quality of life following radiofrequency ablation of dysplastic Barrett’s esophagus
Authors: N. Shaheen, A. Peery, R. Hawes, R. Rothstein, S. Spechler, J. Galanko, M. Campbell, C. Carr, B. Fowler, J. Walsh, A. Siddiqui, A. Infantolino, H. Wolfsen
Journal: Endoscopy (2010)

Background and study aims: The impact of the diagnosis and treatment of dysplastic Barrett's esophagus on quality of life (QoL) is poorly understood. This study assessed the influence of dysplastic Barrett's esophagus on QoL and evaluated whether endoscopic treatment of dysplastic Barrett's esophagus with radiofrequency ablation (RFA) improves QoL.
Electrophysiological parameters indicative of sudden cardiac death in the dog with chronic complete AV-block
Authors: J van Opstal
Journal: Cardiovascular Research (2001)

Background: The dog model of chronic complete AV-block (CAVB) demonstrates a considerable incidence of (witnessed) sudden death (16/117 dogs). In this study we tried to: (1) elucidate the mechanisms of sudden death using an ECG telemetry device and (2) identify retrospectively the risk parameters indicative of this arrhythmogenic death. Methods: Between 1994 and 1998, 78 anesthetized dogs underwent an extensive electrophysiological study including: (1) left- (LV) and right ventricular (RV) monophasic action potential (MAP) recordings to assess ΔMAPD (LV APD minus RV APD) and (2) pacing protocols (PES) to induce torsade de pointes arrhythmias (TdP) at 4–6 weeks CAVB. Eight animals experienced sudden cardiac death (SCD) during the follow-up period (mean 7±3 weeks CAVB). Since the response of the CAVB dog to class III drugs is not uniform we also made comparisons among the SCD group, TdP drug responders and non-responders. For this purpose we selected all animals which (1) received almokalant (n = 15, 0.12 mg/kg/5 min) or ibutilide (n = 9, 0.025 mg/kg/5 min) as an additional challenge to induce TdP and (2) had a follow-up period of at least 4 weeks. Results: Six out of eight SCD dogs showed inducible TdP at baseline. Two of eight dogs had telemetric ECG surveillance and both revealed polymorphic VT as the cause of SCD. Baseline ΔMAPD of the SCD (90±15 ms) was significantly higher than the non-scD group (n = 70, 60±30 ms). Of the 24 dogs which received class III drugs, 12 belonged to the TdP responder group. ΔMAPD of the TdP responder group (80±15 ms) was similar to the SCD group and significantly higher compared to the non-responder group (n = 12, 40±25 ms). QT-time and cycle length of idioventricular rhythm were not different. Conclusion: In the CAVB dog model, SCD is (1) most probably related to TdP while (2) inducible TdP and the measure of ΔMAPD at baseline indicate susceptibility to SCD.
Multitargeted Effects of Statin-Enhanced Thrombolytic Therapy for Stroke With Recombinant Human Tissue-Type Plasminogen Activator in the Rat
Authors: Li Zhang, Zheng Gang Zhang, Guang Liang Ding, Quan Jiang, Xianshuang Liu, He Meng, Ann Hozeska, Chunling Zhang, Lian Li, Dan Morris, Rui Lan Zhang, Mei Lu, Michael Chopp
Journal: Circulation (2005)

Background— Microvascular dysfunction posttreatment of stroke with recombinant human tissue-type plasminogen activator (rht-PA) constrains the therapeutic window to 3 hours. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) promote vascular thrombolysis and reduce the inflammation response. We therefore investigated the neuroprotective effects of a combination of atorvastatin and delayed rht-PA treatment in a rat model of embolic stroke. Methods and Results— Rats subjected to embolic middle cerebral artery occlusion were treated with atorvastatin in combination with rht-PA 4 hours after stroke. Magnetic resonance imaging measurements revealed that combination treatment with atorvastatin and rht-PA blocked the expansion of the ischemic lesion, which improved neurological function compared with saline-treated rats. Real-time reverse transcription–polymerase chain reaction analysis of single endothelial cells isolated by laser-capture microdissection from brain tissue and immunostaining showed that combination treatment downregulated expression of tissue factor, von Willebrand factor, protease-activated receptor-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9, which concomitantly reduced cerebral microvascular thrombosis and enhanced microvascular integrity. Combination treatment did not increase cerebrovascular endothelial nitric oxide synthase (eNOS) levels or eNOS activity, and inhibition of NOS activity with N -nitro- l -arginine methyl ester did not block the beneficial effects of combination treatment on stroke. Furthermore, combination treatment compared with thrombolytic monotherapy increased cerebral blood flow and reduced infarct volume in eNOS-null mice. Conclusions— These data demonstrate that combination treatment with atorvastatin and rht-PA exerts a neuroprotective effect when administered 4 hours after stroke and that the therapeutic benefits are likely attributed to its multitargeted effects on cerebrovascular patency and integrity.
Non-Thiotepa-Based HDT and ASCT for Relapsed/Refractory Secondary Central Nervous System Lymphoma
Authors: I. Shimizu, N. Ichikawa, W. Takeda, T. Kirihara, K. Sato, T. Ueki, Y. Hiroshima, M. Sumi, M. Ueno, H. Kobayashi
Journal: Annals of Oncology (2013)
Lung injury after hepatoenteric ischemia-reperfusion: role of xanthine oxidase.
Authors: V G Nielsen, S Tan, A Weinbroum, A T McCammon, P N Samuelson, S Gelman, D A Parks
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Oxidant stress plays a major role in the pathophysiologic processes associated with ischemia-reperfusion injury. Xanthine oxidase (XO) is often implicated as a significant source of oxidants and increases in the circulation after hepatoenteric ischemia-reperfusion. We hypothesized that pulmonary injury is associated with hepatic ischemia-reperfusion resulting from descending thoracic aorta occlusion-reperfusion (AoOR). We also proposed that this remote pulmonary injury is attenuated through inactivation of circulating and tissue XO by tungstate, implicating an XO-dependent mechanism. Aortic occlusion was established in rabbits (standard or tungstate diet) for 40 min by 2 h reperfusion. Sham operated rabbits (standard or tungstate diet) served as controls. Hepatic reperfusion injury, as manifested by release of the hepatocellular enzyme alanine aminotransferase (ALT), was markedly increased after AoOR. Suprarenal-infrahepatic occlusion failed to increase ALT release. Tungstate pretreatment significantly (p < 0.05) reduced XO activity and ameliorated liver and intestinal injury (p < 0.05). Lung injury, manifested by increased bronchoalveolar lavage (BAL) protein concentration, BAL lactate dehydrogenase (LDH) activity and increased lung edema was significantly associated with liver injury (p < 0.05) and circulating XO activity (p < 0.001). XO inactivation significantly decreased BAL protein concentration, BAL LDH activity, and lung edema (p < 0.05). We conclude that remote pulmonary injury is significantly influenced by the extent of liver injury and circulating XO activity.
Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease
Authors: Coro Paisán-Ruı́z, Shushant Jain, E.Whitney Evans, William P. Gilks, Javier Simón, Marcel van der Brug, Adolfo López de Munain, Silvia Aparicio, Angel Martı́nez Gil, Naheed Khan, Janel Johnson, Javier Ruiz Martinez, David Nicholl, Itxaso Marti Carrera, Amets Saénz Peňa, Rohan de Silva, Andrew Lees, José Félix Martı́-Massó, Jordi Pérez-Tur, Nick W. Wood, Andrew B. Singleton
Journal: Neuron (2004)
Dynamic DNA methylation change in the CpG island region of p15 during human myeloid development
Authors: Kazuo Sakashita, Kenichi Koike, Tatsuya Kinoshita, Masaaki Shiohara, Takehiko Kamijo, Shun’ichiro Taniguchi, Takeo Kubota
Journal: Journal of Clinical Investigation (2001)

We examined the kenetics of p15 methylation and expression during myeloid development. We treated human cord blood CD34+ cells with either GM-CSF alone or in combination with stem cell factor and followed methylation at this locus using bisulfite genomic sequencing. CD34+ cells were found to be either fully methylated or completely unmethylated at 27 CpG dinucleotide sites in exon 1 and at 18 CpG sites in the promoter region of the p15 gene. A time-course study showed that the percentage of the allelic methylation of p15 CpG island increased to approximately 50% to 60% until 7 days after cytokine stimulation, then decreased to less than 10% after 21 days. The methylation was also observed in bone marrow CD34+ cells exposed to GM-CSF. p15 expression varied inversely with methylation. Expression was negligible or at low levels until 14 days, after which it increased substantially. The frequency of myeloid colony-forming cells in the progeny decreased and myeloid-specific markers increased in the later stages. Based on our observations on cells grown with GM-CSF and 5-aza-2'-deoxycytidine, DNA methylation of the p15 promoter region CpG island appears to be associated with proliferation rather than differentiation of normal human myeloid progenitors.
Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system
Authors: E. Dale Abel, Mary-Ellen Boers, Carmen Pazos-Moura, Egberto Moura, Helen Kaulbach, Marjorie Zakaria, Bradford Lowell, Sally Radovick, M. Charles Liberman, Fredric Wondisford
Journal: Journal of Clinical Investigation (1999)

Thyroid hormone receptors (TRs) modulate various physiological functions in many organ systems. The TRα and TRβ isoforms are products of 2 distinct genes, and the β1 and β2 isoforms are splice variants of the same gene. Whereas TRα1 and TRβ1 are widely expressed, expression of the TRβ2 isoform is mainly limited to the pituitary, triiodothyronine-responsive TRH neurons, the developing inner ear, and the retina. Mice with targeted disruption of the entire TRβ locus (TRβ-null) exhibit elevated thyroid hormone levels as a result of abnormal central regulation of thyrotropin, and also develop profound hearing loss. To clarify the contribution of the TRβ2 isoform to the function of the endocrine and auditory systems in vivo, we have generated mice with targeted disruption of the TRβ2 isoform. TRβ2-null mice have preserved expression of the TRα and TRβ1 isoforms. They develop a similar degree of central resistance to thyroid hormone as TRβ-null mice, indicating the important role of TRβ2 in the regulation of the hypothalamic-pituitary-thyroid axis. Growth hormone gene expression is marginally reduced. In contrast, TRβ2-null mice exhibit no evidence of hearing impairment, indicating that TRβ1 and TRβ2 subserve divergent roles in the regulation of auditory function.
Management of cervical dyskaryosis
Authors: W P Soutter
Journal: BMJ (1994)

our observations were incorrect, as Wilmshurst suggests.4There are about 50000 subaqua divers in Britain; about 15 000 would be expected to have a patent foramen ovale.About 100 episodes of neurological decompression sickness occur in Britain each year.A shunt will not necessarily result in decompression sickness, even in experienced divers.'Published evidence suggests that a shunt may increase the risk of a diver developing some form of decompression sickness.This extra risk, however, is small.
Glycerol and the skin: holistic approach to its origin and functions
Authors: J.W. Fluhr, R. Darlenski, C. Surber
Journal: British Journal of Dermatology (2008)

Glycerol is a trihydroxy alcohol that has been included for many years in topical dermatological preparations. In addition, endogenous glycerol plays a role in skin hydration, cutaneous elasticity and epidermal barrier repair. The aquaporin-3 transport channel and lipid metabolism in the pilosebaceous unit have been evidenced as potential pathways for endogenous delivery of glycerol and for its metabolism in the skin. Multiple effects of glycerol on the skin have been reported. The diverse actions of the polyol glycerol on the epidermis include improvement of stratum corneum hydration, skin barrier function and skin mechanical properties, inhibition of the stratum corneum lipid phase transition, protection against irritating stimuli, enhancement of desmosomal degradation, and acceleration of wound-healing processes. Even an antimicrobial effect has been demonstrated. Topical application of glycerol-containing products improves skin properties in diseases characterized by xerosis and impaired epidermal barrier function, such as atopic dermatitis. The increase of epidermal hydration by glycerol is critical in skin conditions aggravated by dry and cold environmental conditions, e.g. winter xerosis. This paper provides a review on effects of glycerol on the skin, the mechanisms of its action, and the potential applications of glycerol in dermatology.
Functional Organization of the Genome May Shape the Species Boundary in the House Mouse
Authors: Václav Janoušek, Pavel Munclinger, Liuyang Wang, Katherine C. Teeter, Priscilla K. Tucker
Journal: Molecular Biology and Evolution (2015)

Genomic features such as rate of recombination and differentiation have been suggested to play a role in species divergence. However, the relationship of these phenomena to functional organization of the genome in the context of reproductive isolation remains unexplored. Here, we examine genomic characteristics of the species boundaries between two house mouse subspecies (Mus musculus musculus/M. m. domesticus). These taxa form a narrow semipermeable zone of secondary contact across Central Europe. Due to the incomplete nature of reproductive isolation, gene flow in the zone varies across the genome. We present an analysis of genomic differentiation, rate of recombination, and functional composition of genes relative to varying amounts of introgression. We assessed introgression using 1,316 autosomal single nucleotide polymorphism markers, previously genotyped in hybrid populations from three transects. We found a significant relationship between amounts of introgression and both genomic differentiation and rate of recombination with genomic regions of reduced introgression associated with higher genomic differentiation and lower rates of recombination, and the opposite for genomic regions of extensive introgression. We also found a striking functional polarization of genes based on where they are expressed in the cell. Regions of elevated introgression exhibit a disproportionate number of genes involved in signal transduction functioning at the cell periphery, among which olfactory receptor genes were found to be the most prominent group. Conversely, genes expressed intracellularly and involved in DNA binding were the most prevalent in regions of reduced introgression. We hypothesize that functional organization of the genome is an important driver of species divergence.
Molecular Imaging of Inflammation in Atherosclerosis With Targeted Ultrasound Detection of Vascular Cell Adhesion Molecule-1
Authors: Beat A. Kaufmann, John M. Sanders, Christopher Davis, Aris Xie, Patrick Aldred, Ian J. Sarembock, Jonathan R. Lindner
Journal: Circulation (2007)

Background— The ability to image vascular inflammatory responses may allow early diagnosis and treatment of atherosclerosis. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) expression with contrast-enhanced ultrasound (CEU) could be used for this purpose. Methods and Results— Attachment of VCAM-1–targeted and control microbubbles to cultured endothelial cells was assessed in a flow chamber at variable shear stress (0.5 to 12.0 dynes/cm 2 ). Microbubble attachment to aortic plaque was determined by en face microscopy of the thoracic aorta 10 minutes after intravenous injection in wild-type or apolipoprotein E–deficient mice on either chow or hypercholesterolemic diet. CEU molecular imaging of the thoracic aorta 10 minutes after intravenous microbubble injection was performed for the same animal groups. VCAM-1–targeted but not control microbubbles attached to cultured endothelial cells, although firm attachment at the highest shear rates (8 to 12 dynes/cm 2 ) occurred only in pulsatile flow conditions. Aortic attachment of microbubbles and targeted CEU signal was very low in control wild-type mice on chow diet. Aortic attachment of microbubbles and CEU signal for VCAM-1–targeted microbubbles differed between treatment groups according to extent of VCAM-1–positive plaque formation (median CEU videointensity, 1.8 [95% CI, 1.2 to 1.7], 3.7 [95% CI, 2.9 to 7.3], 6.8 [95% CI, 3.9 to 7.6], and 11.2 [95% CI, 8.5 to 16.0] for wild-type mice on chow and hypercholesterolemic diet and for apolipoprotein E–deficient mice on chow and hypercholesterolemic diet, respectively; P &lt;0.001). Conclusions— CEU molecular imaging of VCAM-1 is capable of rapidly quantifying vascular inflammatory changes that occur in different stages of atherosclerosis. This method may be potentially useful for early risk stratification according to inflammatory phenotype.
Commentaries on this month's Cardiovascular Controversy: the merits and demerits of animal experimentation From D J Sheridan
Authors: D J Sheridan
Journal: Cardiovascular Research (1994)

Commentaries on this month's Cardiovascular Controversy: the merits and demerits of animal experimentation From D J Sheridan Get access D J Sheridan D J Sheridan Academic Cardiology Unit, St Mary's Hmpital Medical School, London W2, UK. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 7, July 1994, Pages 1113–1114, https://doi.org/10.1093/cvr/28.7.1113b Published: 01 July 1994
Cancer Cell Death Enhances the Penetration and Efficacy of Oncolytic Herpes Simplex Virus in Tumors
Authors: Satoshi Nagano, Jean Yannis Perentes, Rakesh K. Jain, Yves Boucher
Journal: Cancer Research (2008)

Abstract The success of tumor oncolytic virotherapy is limited by the poor penetration of virus in tumors. Interstitial collagen fibers and the narrow spacing between cancer cells are major barriers hindering the movement of large viral particles. To bypass the cellular barrier, we tested the hypothesis that the void space produced by cancer cell apoptosis enhances the initial spread and efficacy of oncolytic herpes simplex virus (HSV). In mice with mammary tumors, apoptosis was induced by doxycycline-regulated expression/activation of CD8/caspase-8, paclitaxel, or paclitaxel plus tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). In both collagen-poor and collagen-rich tumors, apoptosis or necrosis increased the initial intratumoral spread of HSV. Compared with the isolated pattern of HSV infection generally located in the center of control tumors, apoptosis induction and a single i.t. injection of virus produced an interconnected and diffuse pattern of infection, which extended from the tumor center to the periphery. This interconnected pattern of viral infection correlated with the formation of void spaces and channel-like structures in apoptosis-rich tumor areas. We also show that the i.t. injection of HSV after caspase-8 activation or paclitaxel-TRAIL pretreatment retards tumor growth, whereas HSV administration before tumor cell death induction did not improve therapeutic efficacy. Hence, our findings show that the induction of cancer cell death before the injection of oncolytic HSV enhances intratumoral virus delivery/penetration and antitumor efficacy. [Cancer Res 2008;68(10):3795–802]
Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer
Authors: G. Sonpavde, V. Matveev, J.M. Burke, J.R. Caton, M.T. Fleming, T.E. Hutson, M.D. Galsky, W.R. Berry, P. Karlov, J.T. Holmlund, B.A. Wood, M. Brookes, L. Leopold
Journal: Annals of Oncology (2011)