tbuckley/cabot-search huggingface dataset:
Targeting CCR8 Induces Protective Antitumor Immunity and Enhances Vaccine-Induced Responses in Colon Cancer
Authors: Daniel O. Villarreal, Andrew L'Huillier, Susan Armington, Cristina Mottershead, Elena V. Filippova, Brandon D. Coder, Robert G. Petit, Michael F. Princiotta
Journal: Cancer Research (2018)

Abstract CCR8 is a chemokine receptor expressed principally on regulatory T cells (Treg) and is known to be critical for CCR8+ Treg-mediated immunosuppression. Recent studies have demonstrated that CCR8 is uniquely upregulated in human tumor-resident Tregs of patients with breast, colon, and lung cancer when compared with normal tissue-resident Tregs. Therefore, CCR8+ tumor-resident Tregs are rational targets for cancer immunotherapy. Here, we demonstrate that mAb therapy targeting CCR8 significantly suppresses tumor growth and improves long-term survival in colorectal tumor mouse models. This antitumor activity correlated with increased tumor-specific T cells, enhanced infiltration of CD4+ and CD8+ T cells, and a significant decrease in the frequency of tumor-resident CD4+CCR8+ Tregs. Tumor-specific CD8+ T cells displayed lower expression of exhaustion markers as well as increased functionality upon restimulation. Treatment with anti-CCR8 mAb prevented de novo induction and suppressive function of Tregs without affecting CD8+ T cells. Initial studies explored a combinatorial regimen using anti-CCR8 mAb therapy and a Listeria monocytogenes–based immunotherapy. Anti-CCR8 mAb therapy synergized with L. monocytogenes–based immunotherapy to significantly delay growth of established tumors and to prolong survival. Collectively, these findings identify CCR8 as a promising new target for tumor immunotherapy and provide a strong rationale for further development of this approach, either as a monotherapy or in combination with other immunotherapies. Significance: Inhibition of CCR8 represents a promising new cancer immunotherapy strategy that modulates tumor-resident regulatory T cells to enhance antitumor immunity and prolong patient survival. Cancer Res; 78(18); 5340–8. ©2018 AACR.
A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for Grading of Coronary Artery Disease, Council on Cardiovascular Surgery, American Heart Association
Authors: WGAusten, JEEdwards, RLFrye, GGGensini, VLGott, LSGriffith, DCMcGoon, MLMurphy, BBRoe
Journal: Circulation (1975)
Nonheavy Drinking and Worsening of Noninvasive Fibrosis Markers in Nonalcoholic Fatty Liver Disease
Authors: Yoosoo Chang, Yong Kyun Cho, Yejin Kim, Eunju Sung, Jiin Ahn, Hyun‐Suk Jung, Kyung Eun Yun, Hocheol Shin, Seungho Ryu
Journal: Hepatology (2018)

The effect of modest alcohol consumption on fibrosis progression in the general population with nonalcoholic fatty liver disease (NAFLD) remains unclear. We examined the association of nonheavy alcohol consumption with worsening of noninvasive fibrosis indices in a large‐scale, low‐risk population with NAFLD. A cohort study was performed in 58,927 Korean adults with NAFLD and low fibrosis scores who were followed for a median of 4.9 years. Non‐, light, and moderate drinkers were defined as 0 g/day, 1‐9.9 g/day, and 10‐29.9 g/day (10‐19.9 g/day for women), respectively. Progression from low to intermediate or high probability of advanced fibrosis was assessed using noninvasive indices including NAFLD fibrosis score (NFS) and Fibrosis‐4 Index (FIB‐4). A parametric proportional hazards model was used to estimate the multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). During 347,925.4 person‐years of follow‐up, 5,630 subjects with low FIB‐4 progressed to intermediate or high FIB‐4. The multivariable‐adjusted HRs (95% CI) for worsening of FIB‐4 comparing light and moderate drinkers with nondrinkers were 1.06 (0.98‐1.16) and 1.29 (1.18‐1.40), respectively. Similarly, using NFS, corresponding HRs (95% CI) comparing light and moderate drinkers with nondrinkers were 1.09 (1.02‐1.16) and 1.31 (1.23‐1.40), respectively. Furthermore, the association of moderate drinkers with worsening of either FIB‐4 or NFS remained significant after introducing alcohol use and confounders treated as time‐varying covariates. Conclusion: In this large‐scale cohort of young and middle‐aged individuals with NAFLD, nonheavy alcohol consumption, especially moderate alcohol consumption, was significantly and independently associated with worsening of noninvasive markers of fibrosis, indicating that even moderate alcohol consumption might be harmful.
Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society—Lancet Commission
Authors: Linda-Gail Bekker, George Alleyne, Stefan Baral, Javier Cepeda, Demetre Daskalakis, David Dowdy, Mark Dybul, Serge Eholie, Kene Esom, Geoff Garnett, Anna Grimsrud, James Hakim, Diane Havlir, Michael T Isbell, Leigh Johnson, Adeeba Kamarulzaman, Parastu Kasaie, Michel Kazatchkine, Nduku Kilonzo, Michael Klag, Marina Klein, Sharon R Lewin, Chewe Luo, Keletso Makofane, Natasha K Martin, Kenneth Mayer, Gregorio Millett, Ntobeko Ntusi, Loyce Pace, Carey Pike, Peter Piot, Anton Pozniak, Thomas C Quinn, Jurgen Rockstroh, Jirair Ratevosian, Owen Ryan, Serra Sippel, Bruno Spire, Agnes Soucat, Ann Starrs, Steffanie A Strathdee, Nicholas Thomson, Stefano Vella, Mauro Schechter, Peter Vickerman, Brian Weir, Chris Beyrer
Journal: The Lancet (2018)
Extracellular Matrix Glycoprotein Biglycan Enhances Vascular Smooth Muscle Cell Proliferation and Migration
Authors: RyokoShimizu-Hirota, HiroyukiSasamura, MariKuroda, EmiKobayashi, MatsuhikoHayashi, TakaoSaruta
Journal: Circulation Research (2004)

Proteoglycans are produced and secreted by vascular smooth muscle cells, but the pathophysiological role of these glycoproteins in the vasculature is an enigma. Because the small leucine-rich proteoglycan (SLRP) biglycan is overexpressed in arteriosclerotic lesions, we produced mice constitutively overexpressing biglycan in the vascular smooth muscle, in order to examine the effects on vascular pathology. In the aorta and renal vasculature, increased vascular proliferation was seen both in the basal state and after infusion of angiotensin II (Ang II) in the transgenic mice compared with wild-type controls. In addition, the combination of biglycan overexpression and Ang II infusion resulted in marked increases in vascular smooth muscle cell proliferation and migration in the coronary arteries, as well as increases in fibrosis surrounding the vessels. In vitro, biglycan caused an increase in thymidine incorporation and migration of vascular smooth muscle cells, whereas these parameters were unchanged or red...
Mildly Oxidized LDL Evokes a Sustained Ca2+-Dependent Retraction of Vascular Smooth Muscle Cells
Authors: NathalieAugé, GuylèneFitoussi, Jean-LoupBascands, Marie-ThérèsePieraggi, DidierJunquero, PhilippeValet, Jean-PierreGirolami, RobertSalvayre, AnneNègre-Salvayre
Journal: Circulation Research (1996)

Oxidized low density lipoprotein (LDL) is thought to play a major role in atherogenesis. Atherosclerotic arteries exhibit structural changes associated with profound alterations in vascular tone that are potentially involved in arterial spasm and ischemic heart disease. We report here the role of oxidized LDL in the retraction of vascular smooth muscle cells. Mildly oxidized LDL elicited a broad and sustained peak in cytosolic calcium concentration ([Ca2+]i) in cultured arterial smooth muscle cells. Concomitant with the [Ca2+]i rise, oxidized LDL evoked a sustained and intense retraction of smooth muscle cells, as shown by the changes in cross-sectional area of single cells. Cell retraction was dependent on time, the concentration of oxidized LDL, and the level of LDL oxidation (native LDL induced neither a significant [Ca2+]i rise nor cell retraction). Oxidized LDL but not native LDL also elicited a delayed (12±2 hours) and sustained (14±2 hours) increase in isometric tension in deendothelialized arteria...
Complete Isolation of Left Atrium Surrounding the Pulmonary Veins
Authors: FeifanOuyang, DietmarBänsch, SabineErnst, AnselmSchaumann, HitoshiHachiya, MinglongChen, JulianChun, PeterFalk, AfsanehKhanedani, MatthiasAntz, Karl-HeinzKuck
Journal: Circulation (2004)

Background— Paroxysmal atrial fibrillation (PAF) can be eliminated with continuous circular lesions (CCLs) around the pulmonary veins (PVs), but it is unclear whether all PVs are completely isolated. Methods and Results— Forty-one patients with symptomatic PAF underwent 3D mapping, and all PV ostia were marked on the 3D map based on venography. Irrigated radiofrequency energy was applied at a distance from the PV ostia guided by 2 Lasso catheters placed within the ipsilateral superior and inferior PVs. The mean radiofrequency duration was 1550±511 seconds for left-sided PVs and 1512±506 seconds for right-sided PVs. After isolation, automatic activity was observed in the right-sided PVs in 87.8% and in the left-sided PVs in 80.5%. During the procedure, a spontaneous or induced PV tachycardia (PVT) with a cycle length of 189±29 ms was observed in 19 patients. During a mean follow-up of 6 months, atrial tachyarrhythmias recurred in 10 patients. Nine patients underwent a repeat procedure. Conduction gaps in t...
FDA Prods “Clean Meat” Discussion
Authors: Rebecca Voelker
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Myocyte Enhancer Factor 2 Mediates Vascular Inflammation via the p38-Dependent Pathway
Authors: EtsuSuzuki, HiroshiSatonaka, HiroakiNishimatsu, ShigeyoshiOba, RyoTakeda, MasaoOmata, ToshiroFujita, RyozoNagai, YasunobuHirata
Journal: Circulation Research (2004)

Although it has been established that myocyte enhancer factor 2 (MEF2) plays pivotal roles in the development of the cardiovascular system as well as skeletal muscle cells, little is known of its role in vascular inflammatory diseases such as atherosclerosis and restenosis after angioplasty. To investigate the role of MEF2 in vascular inflammation and that of p38 in the activation of MEF2, we infected cultured rat vascular smooth muscle cells (VSMCs) with an adenovirus construct expressing a dominant-negative mutant of MEF2A (MEF2ASA) or mitogen-activated protein kinase kinase 6 (MEK6AA), and examined their effects on the expression of monocyte chemoattractant protein-1 (MCP-1), which is known to play important roles in vascular inflammation. We also examined the role of MEF2 in vivo using a rat model of transluminal wire-induced injury of the femoral artery. Angiotensin II (Ang II)–induced expression of MCP-1 mRNA was significantly inhibited by infection with adenoviruses encoding MEF2ASA (AdMEF2ASA) or ...
Multiple Modes of Adaptation: Regulatory and Structural Evolution in a Small Heat Shock Protein Gene
Authors: Sumaetee Tangwancharoen, Gary W Moy, Ronald S Burton
Journal: Molecular Biology and Evolution (2018)

Thermal tolerance is a key determinant of species distribution. Despite much study, the genetic basis of adaptive evolution of thermal tolerance, including the relative contributions of transcriptional regulation versus protein evolution, remains unclear. Populations of the intertidal copepod Tigriopus californicus are adapted to local thermal regimes across their broad geographic range. Upon thermal stress, adults from a heat tolerant southern population, San Diego (SD), upregulate several heat shock proteins (HSPs) to higher levels than those from a less tolerant northern population, Santa Cruz (SC). Suppression of a specific HSP, HSPB1, significantly reduces T. californicus survival following acute heat stress. Sequencing of HSPB1 revealed population specific nucleotide substitutions in both promoter and coding regions of the gene. HSPB1 promoters from heat tolerant populations contain two canonical heat shock elements (HSEs), the binding sites for heat shock transcription factor (HSF), whereas less tolerant populations have mutations in these conserved motifs. Allele specific expression of HSPB1 in F1 hybrids between tolerant and less tolerant populations showed significantly biased expression favoring alleles from tolerant populations and supporting the adaptive divergence in these cis-regulatory variants. The functional impact of population-specific nonsynonymous substitutions in HSPB1 coding sequences was tested by assessing the thermal stabilization properties of SD versus SC HSPB1 protein variants. Recombinant HSPB1 from the southern SD population showed greater capacity for protecting protein structure under elevated temperature. Our results indicate that both regulatory and protein coding sequence evolution within a single gene appear to contribute to thermal tolerance phenotypes and local adaptation among conspecific populations.
Abstract 14409: Cardiac Angiogenesis and Arteriogenesis Suppression After Myocardial Infarction Through Activation of Dipeptidyl Peptidase I
Authors: Mikhail A Kolpakov, Bahman Hooshdaran, Xinji Guo, Khadija Rafiq, Liudmila Vlasenko, Yulia V Bashkirova, Tao Wang, Zhao Qi, Venkata N Garikipati, Raj Kishore, Abdelkarim Sabri
Journal: Circulation (2016)

Introduction: Inflammatory cells participation in new blood vessel formation is critical for tissue repair in response to tissue injury, such as myocardial infarction (MI). However, the mechanism(s...
Clofazimine improves clinical outcomes in multidrug-resistant tuberculosis: a randomized controlled trial
Authors: H. Duan, X. Chen, Z. Li, Y. Pang, W. Jing, P. Liu, T. Wu, C. Cai, J. Shi, Z. Qin, H. Yin, C. Qiu, C. Li, Y. Xia, W. Chen, Z. Ye, Z. Li, G. Chen, S. Wang, Y. Liu, L. Chu, M. Zhu, T. Xu, Q. Wang, J. Wang, Y. Du, J. Wang, N. Chu, S. Xu
Journal: Clinical Microbiology and Infection (2018)

ObjectivesWe carried out a randomized multicentre study in China to investigate whether the clofazimine would improve the efficacy of the standardized regimen in patients with multidrug-resistant tuberculosis (MDR-TB).MethodsPatients with MDR-TB managed in 17 TB specialist hospitals in China between September 2009 and September 2011 were randomly assigned to the treatment groups at enrolment. In the intervention group, 100 mg clofazimine per day was added to the standardized regimen. The primary outcome was the proportion of patients with successful outcomes.ResultsFrom the 156 patients that were screened, 74 were assigned to the control group and 66 to the clofazimine group. Of the 66 cases analysed for clinical outcome in the clofazimine group, 36 patients were cured, and seven completed treatment, yielding a favourable outcome rate of 65.1%. The proportion of patients with favourable outcomes receiving the control regimen was 47.3% (35/74), which was significantly lower than that in the clofazimine group (p 0.034, relative risk 0.661, 95% CI 0.243–0.949).ConclusionsThe addition of clofazimine to the standard regimen improved the treatment of MDR-TB.
GP fails in legal bid to prevent patient seeing GMC report
Authors: Clare Dyer
Journal: BMJ (2018)

A GP who took legal action to try to stop the General Medical Council releasing an expert’s report to a patient who planned to sue him has lost his case in the Court of Appeal, after initially winning in the High Court.1

The patient, who has bladder cancer, complained to the GMC that the GP’s treatment of him led to a year’s avoidable delay in his diagnosis. Both patient and doctor have been made anonymous in the court judgments to protect their identities.

The GMC commissioned an expert’s report, which concluded that the doctor’s care had been below—but not seriously below—the standard …
Risankizumab in patients with moderate to severe Crohn's disease: an open-label extension study
Authors: Brian G Feagan, Julián Panés, Marc Ferrante, Arthur Kaser, Geert R D'Haens, William J Sandborn, Edouard Louis, Markus F Neurath, Denis Franchimont, Olivier Dewit, Ursula Seidler, Kyung-Jo Kim, Christian Selinger, Steven J Padula, Ivona Herichova, Anne M Robinson, Kori Wallace, Jun Zhao, Mukul Minocha, Ahmed A Othman, Adina Soaita, Sudha Visvanathan, David B Hall, Wulf O Böcher
Journal: The Lancet. Gastroenterology & hepatology (2018)
Abstract 16515: Reperfusion Therapy With Sacubitril/Valsartan Attenuates Infarct Size and Preserves Left Ventricular Function in a Rabbit Model of Myocardial Infarction
Authors: Juan Torrado, Chad Cain, Ramzi A Ockaili, Francisco Romeo, John Nestler, Teja Devarakonda, Anindita Das, Fadi N Salloum
Journal: Circulation (2017)

Background:  The combination drug sacubitril (neprilysin inhibitor)/valsartan (Ang-II receptor blocker) is FDA-approved for treatment of HFrEF patients and NYHA class II-IV symptoms. Whether SAC/VAL attenuates acute myocardial infarction (MI) and related adverse cardiac remodeling is unknown.   Methods and Results:  Dose-finding pharmacodynamic studies were performed in adult male NZW rabbits (~2.5 kg). After treatment with SAC/VAL or placebo (volume-matched water), blood pressure was monitored via ear artery for 6 hours. A subset of rabbits received a bolus of ANP 3h or 6h after treatment to determine cGMP plasma levels and optimal SAC/VAL dose. In the experimental MI group, the heart was exposed through a left thoracotomy for implantation of an inflatable balloon occluder on top of the left coronary artery secured on the LV wall. Seven days later, rabbits were sedated (4 mg/kg diazepam) and underwent conscious MI with 45 min of ischemia by balloon inflation followed by 72h of reperfusion. LV function and infarct size were assessed by echocardiography and TTC staining, respectively. Plasma cardiac troponin levels were measured 2h post MI. At the onset of reperfusion, rabbits were randomized to oral treatment with SAC/VAL (20 mg/kg), valsartan (VAL, 9.1 mg/kg) or placebo. The SAC/VAL dose was based on hemodynamic response and plasma cGMP at 3h (Fig. A). There was a significant drop in mean blood pressure with SAC/VAL at 1h and 2h after treatment at reperfusion, which returned to baseline by 4h (Fig. B). Compared to placebo, SAC/VAL and VAL significantly reduced infarct size (Fig. C) and plasma cardiac troponin (Fig. D), however, only SAC/VAL preserved LV function (Fig. E) at 72h post MI.   Conclusion:  Reperfusion therapy with SAC/VAL offers acute infarct-sparing benefits similar to VAL, however, LV function at 72h post MI is significantly preserved with SAC/VAL compared to VAL, which may indicate superior long-term benefits of SAC/VAL in prevention of MI-induced heart failure.
Decreased Total Interstitial Inflammation with Higher Mycophenolate Mofetil Dose after Kidney Transplantation
Authors: Karlo Mihovilovic, Petar Senjug, Bojana Maksimovic, Danica Galessic Ljubanovic, Renata Zunec, Biserka Palfi, Mladen Knotek
Journal: Journal of the American Society of Nephrology (2014)
Ataluren, a New Therapeutic for Alpha-1 Antitrypsin–Deficient Individuals with Nonsense Mutations
Authors: Emer P. Reeves, Ciara A. O’Dwyer, Danielle M. Dunlea, Mark R. Wormald, Padraig Hawkins, Mohammad Alfares, Darrell N. Kotton, Steven M. Rowe, Andrew A. Wilson, Noel G. McElvaney
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Figure 1).This injurious inflation pattern is known to cause overstretch and tidal recruitment in dependent, atelectatic lung, and thereby worsen dependent lung injury (7-9).Reverse triggering increased dependent lung stretch equivalent to that applied by VT of up to 15 ml/kg during muscle paralysis, despite a constant VT (Figure 2).Second, the magnitude of negative swing in Pes during reverse triggering is proportional to the local lung stretch in dependent lung, reflecting greater propensity to injury.Monitoring Pes or electrical activity of diaphragm could contribute in two ways.Each of these modalities increases the recognition of reverse triggering, and they quantify the magnitude of inspiratory muscle force during reverse triggering.Although reverse triggering associated with breath stacking is readily detected, in the absence of breath stacking it is likely to be unnoticed by clinicians relying on standard waveforms (e.g., airway pressure and flow).In addition, it will be underestimated when VT is controlled (4).Reverse triggering occurs in deeply sedated patients, a scenario in which clinicians consider the risk for asynchrony to be minimal (4), in contrast to easily detected vigorous effort, which is widely recognized to be harmful (2, 10).Thus, sedation may reduce harm from vigorous effort but increase the incidence of subtle and unsuspected reverse triggering.Finally, estimation of inspiratory muscle force during reverse triggering may be important to decrease dependent lung stretch and potentially lessen injury.It is uncertain whether the inflation pattern associated with reverse triggering is also observed with other ventilator modes.In conclusion, during reverse triggering, injurious inflation occurred in dependent lung despite the constant overall VT, and dependent lung stretch was proportional to the negative deflection in Pes.Early recognition of reverse triggering may be beneficial.