tbuckley/cabot-search huggingface dataset:
Human CTL Epitopes Prostatic Acid Phosphatase-3 and Six-Transmembrane Epithelial Antigen of Prostate-3 as Candidates for Prostate Cancer Immunotherapy
Authors: Arthur Machlenkin, Adrian Paz, Erez Bar Haim, Ofir Goldberger, Eran Finkel, Boaz Tirosh, Ilan Volovitz, Ezra Vadai, Gilles Lugassy, Shmuel Cytron, Francois Lemonnier, Esther Tzehoval, Lea Eisenbach
Journal: Cancer Research (2005)

Abstract Specific immunotherapy of prostate cancer may be an alternative or be complementary to other approaches for treatment of recurrent or metastasized disease. This study aims at identifying and characterizing prostate cancer–associated peptides capable of eliciting specific CTL responses in vivo. Evaluation of peptide-induced CTL activity in vitro was done following immunization of HLA-A2 transgenic (HHD) mice. An in vivo tumor rejection was tested by adoptive transfer of HHD immune lymphocytes to nude mice bearing human tumors. To confirm the existence of peptide-specific CTL precursors in human, lymphocytes from healthy and prostate cancer individuals were stimulated in vitro in the presence of these peptides and CTL activities were assayed. Two novel immunogenic peptides derived from overexpressed prostate antigens, prostatic acid phosphatase (PAP) and six-transmembrane epithelial antigen of prostate (STEAP), were identified; these peptides were designated PAP-3 and STEAP-3. Peptide-specific CTLs lysed HLA-A2.1+ LNCaP cells and inhibited tumor growth on adoptive immunotherapy. Furthermore, peptide-primed human lymphocytes derived from healthy and prostate cancer individuals lysed peptide-pulsed T2 cells and HLA-A2.1+ LNCaP cells. Based on the results presented herein, PAP-3 and STEAP-3 are naturally processed CTL epitopes possessing anti–prostate cancer reactivity in vivo and therefore may constitute vaccine candidates to be investigated in clinical trials.
Localizing Gray Matter Deficits in Late-Onset Depression Using Computational Cortical Pattern Matching Methods
Authors: Martina Ballmaier, Anand Kumar, Paul M. Thompson, Katherine L. Narr, Helen Lavretsky, Laverne Estanol, Heather DeLuca, Arthur W. Toga
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors used magnetic resonance imaging and an image analysis technique known as cortical pattern matching to map cortical gray matter deficits in elderly depressed patients with an illness onset after age 60 (late-onset depression). METHOD: Seventeen patients with late-onset depression (11 women and six men; mean age=75.24, SD=8.52) and 17 group-matched comparison subjects (11 women and six men; mean age=73.88, SD=7.61) were included. Detailed spatial analyses of gray matter were conducted across the entire cortex by measuring local proportions of gray matter at thousands of homologous cortical surface locations in each subject, and these patterns were matched across subjects by using elastic transformations to align sulcal topography. To visualize regional changes, statistical differences were mapped at each cortical surface location in three dimensions. RESULTS: The late-onset depression group exhibited significant gray matter deficits in the right lateral temporal cortex and the right parietal cortex, where decreases were most pronounced in sensorimotor regions. The statistical maps also showed gray matter deficits in the same regions of the left hemisphere that approached significance after permutation testing. No significant group differences were detected in frontal cortices or any other anatomical region. CONCLUSIONS: Regionally specific decreases of gray matter occur in late-onset depression, supporting the hypothesis that this subset of elderly patients with major depression presents with certain unique neuroanatomical abnormalities that may differ from patients with an earlier onset of illness.
Comparing Endovascular and Open Repair of Abdominal Aortic Aneurysm
Authors: Ilias Dalainas
Journal: JAMA (2010)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Mdm2 and Aurora Kinase A Inhibitors Synergize to Block Melanoma Growth by Driving Apoptosis and Immune Clearance of Tumor Cells
Authors: Anna E. Vilgelm, Jeff S. Pawlikowski, Yan Liu, Oriana E. Hawkins, Tyler A. Davis, Jessica Smith, Kevin P. Weller, Linda W. Horton, Colt M. McClain, Gregory D. Ayers, David C. Turner, David C. Essaka, Clinton F. Stewart, Jeffrey A. Sosman, Mark C. Kelley, Jeffrey A. Ecsedy, Jeffrey N. Johnston, Ann Richmond
Journal: Cancer Research (2014)

Therapeutics that induce cancer cell senescence can block cell proliferation and promote immune rejection. However, the risk of tumor relapse due to senescence escape may remain high due to the long lifespan of senescent cells that are not cleared. Here, we show how combining a senescence-inducing inhibitor of the mitotic kinase Aurora A (AURKA) with an MDM2 antagonist activates p53 in senescent tumors harboring wild-type 53. In the model studied, this effect is accompanied by proliferation arrest, mitochondrial depolarization, apoptosis, and immune clearance of cancer cells by antitumor leukocytes in a manner reliant upon Ccl5, Ccl1, and Cxcl9. The AURKA/MDM2 combination therapy shows adequate bioavailability and low toxicity to the host. Moreover, the prominent response of patient-derived melanoma tumors to coadministered MDM2 and AURKA inhibitors offers a sound rationale for clinical evaluation. Taken together, our work provides a preclinical proof of concept for a combination treatment that leverages both senescence and immune surveillance to therapeutic ends.
Systems pharmacology and genome medicine: a future perspective
Authors: Aislyn D Wist, Seth I Berger, Ravi Iyengar
Journal: Genome Medicine (2009)

Genome medicine uses genomic information in the diagnosis of disease and in prescribing treatment. This transdisciplinary field brings together knowledge on the relationships between genetics, pathophysiology and pharmacology. Systems pharmacology aims to understand the actions and adverse effects of drugs by considering targets in the context of the biological networks in which they exist. Genome medicine forms the base on which systems pharmacology can develop. Experimental and computational approaches enable systems pharmacology to obtain holistic, mechanistic information on disease networks and drug responses, and to identify new drug targets and specific drug combinations. Network analyses of interactions involved in pathophysiology and drug response across various scales of organization, from molecular to organismal, will allow the integration of the systems-level understanding of drug action with genome medicine. The interface of the two fields will enable drug discovery for personalized medicine. Here we provide a perspective on the questions and approaches that drive the development of these new interrelated fields.
COL4A3/COL4A4 Mutations and Features in Individuals with Autosomal Recessive Alport Syndrome
Authors: Helen Storey, Judy Savige, Vanessa Sivakumar, Stephen Abbs, Frances A. Flinter
Journal: Journal of the American Society of Nephrology (2013)

Alport syndrome is an inherited disease characterized by hematuria, progressive renal failure, hearing loss, and ocular abnormalities. Autosomal recessive Alport syndrome is suspected in consanguineous families and when female patients develop renal failure. Fifteen percent of patients with Alport syndrome have autosomal recessive inheritance caused by two pathogenic mutations in either COL4A3 or COL4A4. Here, we describe the mutations and clinical features in 40 individuals including 9 children and 21 female individuals (53%) with autosomal recessive inheritance indicated by the detection of two mutations. The median age was 31 years (range, 6–54 years). The median age at end stage renal failure was 22.5 years (range, 10–38 years), but renal function was normal in nine adults (29%). Hearing loss and ocular abnormalities were common (23 of 35 patients [66%] and 10 of 18 patients [56%], respectively). Twenty mutation pairs (50%) affected COL4A3 and 20 pairs affected COL4A4. Of the 68 variants identified, 39 were novel, 12 were homozygous changes, and 9 were present in multiple individuals, including c.2906C>G (p.(Ser969*)) in COL4A4, which was found in 23% of the patients. Thirty-six variants (53%) resulted directly or indirectly in a stop codon, and all 17 individuals with early onset renal failure had at least one such mutation, whereas these mutations were less common in patients with normal renal function or late-onset renal failure. In conclusion, patient phenotypes may vary depending on the underlying mutations, and genetic testing should be considered for the routine diagnosis of autosomal recessive Alport syndrome.
Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer
Authors: Krasimira Aleksandrova, Heiner Boeing, Ute Nöthlings, Mazda Jenab, Veronika Fedirko, Rudolf Kaaks, Annekatrin Lukanova, Antonia Trichopoulou, Dimitrios Trichopoulos, Paolo Boffetta, Elisabeth Trepo, Sabine Westhpal, Talita Duarte-Salles, Magdalena Stepien, Kim Overvad, Anne Tjφnneland, Jytte Halkjær, Marie-Christine Boutron-Ruault, Laure Dossus, Antoine Racine, Pagona Lagiou, Christina Bamia, Vassiliki Benetou, Claudia Agnoli, Domenico Palli, Salvatore Panico, Rosario Tumino, Paolo Vineis, Bas Bueno-de-Mesquita, Petra H. Peeters, Inger Torhild Gram, Eiliv Lund, Elisabete Weiderpass, Ramón J. Quirós, Antonio Agudo, María-José Sánchez, Diana Gavrila, Aurelio Barricarte, Miren Dorronsoro, Bodil Ohlsson, Björn Lindkvist, Anders Johansson, Malin Sund, Kay-Tee Khaw, Nicholas Wareham, Ruth C. Travis, Elio Riboli, Tobias Pischon
Journal: Hepatology (2014)

Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137), or IBD (n=34). Using risk-set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL-6, C-peptide, and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations=1.22; 95% CI=1.02-1.46; P=0.03; 1.90; 95% CI=1.30-2.77; P=0.001; 2.25; 95% CI=1.43-3.54; P=0.0005; and 2.09; 95% CI=1.19-3.67; P=0.01, respectively). CRP was associated also with risk of GBTC (IRR=1.22; 95% CI=1.05-1.42; P=0.01). GLDH was associated with risks of HCC (IRR=1.62; 95% CI=1.25-2.11; P=0.0003) and IBD (IRR=10.5; 95% CI=2.20-50.90; P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide, and non-HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.
Impact of Activated Vitamin D and Race on Survival among Hemodialysis Patients
Authors: Myles Wolf, Joseph Betancourt, Yuchiao Chang, Anand Shah, Ming Teng, Hector Tamez, Orlando Gutierrez, Carlos A. Camargo, Michal Melamed, Keith Norris, Meir J. Stampfer, Neil R. Powe, Ravi Thadhani
Journal: Journal of the American Society of Nephrology (2008)

Contrary to most examples of disparities in health outcomes, black patients have improved survival compared with white patients after initiating hemodialysis. Understanding potential explanations for this observation may have important clinical implications for minorities in general. This study tested the hypothesis that greater use of activated vitamin D therapy accounts for the survival advantage observed in black and Hispanic patients on hemodialysis. In a prospective cohort of non-Hispanic white (n = 5110), Hispanic white (n = 979), and black (n = 3214) incident hemodialysis patients, higher parathyroid hormone levels at baseline were the primary determinant of prescribing activated vitamin D therapy. Median parathyroid hormone was highest among black patients, who were most likely to receive activated vitamin D and at the highest dosage. One-year mortality was lower in black and Hispanic patients compared with white patients (16 and 16 versus 23%; P < 0.01), but there was significant interaction between race and ethnicity, activated vitamin D therapy, and survival. In multivariable analyses of patients treated with activated vitamin D, black patients had 16% lower mortality compared with white patients, but the difference was lost when adjusted for vitamin D dosage. In contrast, untreated black patients had 35% higher mortality compared with untreated white patients, an association that persisted in several sensitivity analyses. In conclusion, therapy with activated vitamin D may be one potential explanation for the racial differences in survival among hemodialysis patients. Further studies should determine whether treatment differences based on biologic differences contribute to disparities in other conditions.
<i>Zbtb46</i> expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages
Authors: Ansuman T. Satpathy, Wumesh KC, Jörn C. Albring, Brian T. Edelson, Nicole M. Kretzer, Deepta Bhattacharya, Theresa L. Murphy, Kenneth M. Murphy
Journal: The Journal of Experimental Medicine (2012)

Distinguishing dendritic cells (DCs) from other cells of the mononuclear phagocyte system is complicated by the shared expression of cell surface markers such as CD11c. In this study, we identified Zbtb46 (BTBD4) as a transcription factor selectively expressed by classical DCs (cDCs) and their committed progenitors but not by plasmacytoid DCs (pDCs), monocytes, macrophages, or other lymphoid or myeloid lineages. Using homologous recombination, we replaced the first coding exon of Zbtb46 with GFP to inactivate the locus while allowing detection of Zbtb46 expression. GFP expression in Zbtb46gfp/+ mice recapitulated the cDC-specific expression of the native locus, being restricted to cDC precursors (pre-cDCs) and lymphoid organ– and tissue-resident cDCs. GFP+ pre-cDCs had restricted developmental potential, generating cDCs but not pDCs, monocytes, or macrophages. Outside the immune system, Zbtb46 was expressed in committed erythroid progenitors and endothelial cell populations. Zbtb46 overexpression in bone marrow progenitor cells inhibited granulocyte potential and promoted cDC development, and although cDCs developed in Zbtb46gfp/gfp (Zbtb46 deficient) mice, they maintained expression of granulocyte colony-stimulating factor and leukemia inhibitory factor receptors, which are normally down-regulated in cDCs. Thus, Zbtb46 may help enforce cDC identity by restricting responsiveness to non-DC growth factors and may serve as a useful marker to identify rare cDC progenitors and distinguish between cDCs and other mononuclear phagocyte lineages.
Inhibition of mast cell PGD<sub>2</sub>release protects against mannitol-induced airway narrowing
Authors: J. D. Brannan, M. Gulliksson, S. D. Anderson, N. Chew, J. P. Seale, M. Kumlin
Journal: European Respiratory Journal (2006)

Mannitol inhalation increases urinary excretion of 9alpha,11beta-prostaglandin F2 (a metabolite of prostaglandin D2 and marker of mast cell activation) and leukotriene E4. The present study tested the hypothesis that beta2-adrenoreceptor agonists and disodium cromoglycate (SCG) protect against mannitol-induced bronchoconstriction by inhibition of mast cell mediator release. Fourteen asthmatic subjects inhaled mannitol (mean dose 252+/-213 mg) in order to induce a fall in forced expiratory volume in one second (FEV1) of > or = 25%. The same dose was given 15 min after inhalation of formoterol fumarate (24 microg), SCG (40 mg) or placebo. Pre- and post-challenge urine samples were analysed by enzyme immunoassay for 9alpha,11beta-prostaglandin F2 and leukotriene E4. The maximum fall in FEV1 of 32+/-10% on placebo was reduced by 95% following formoterol and 63% following SCG. Following placebo, there was an increase in median urinary 9alpha,11beta-prostaglandin F2 concentration from 61 to 92 ng.mmol creatinine(-1), but no significant increase in 9alpha,11beta-prostaglandin F2 concentration in the presence of either formoterol (69 versus 67 ng.mmol creatinine(-1)) or SCG (66 versus 60 ng.mmol creatinine(-1)). The increase in urinary leukotriene E4 following placebo (from 19 to 31 ng.mmol creatinine(-1)) was unaffected by the drugs. These results support the hypothesis that the drug effect on airway response to mannitol is due to inhibition of mast cell prostaglandin D2 release.
Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheumatoid arthritis
Authors: K A Guthrie, N R Tishkevich, J L Nelson
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: Some patients with rheumatoid arthritis (RA) lack RA-associated human leukocyte antigen (HLA) alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results. Methods: We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium (NARAC). Results: Among 620 patients with 1 or both parents having a HLA genotype, patients with RA informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs NIPA revealed no significant difference (27% vs 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset &lt;45 years DR4-encoding NIMA was increased compared to NIPA; among women ⩾45 years at onset the reverse was observed (31% vs 16% compared to 10% vs 60%, p = 0.008). DR4 encoding NIMA vs NIPA did not differ in men. The SE did not differ in men or women. Conclusions: Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA.
Lipid Changes in the Eye Concomitant with the Development of Atherosclerosis in the Aorta in the Rabbit
Authors: HENRY G. ROSCOE, ADOLPH W. VOGEL
Journal: Circulation Research (1968)

The lipid changes that occur in the eyes and aortas of male Dutch belted rabbits maintained on 1% dietary cholesterol for 1 to 3 months were studied. In the cornea, iris, ciliary body, and aorta, the most noteworthy lipid change was in tissue cholesterol, which increased with increased time of feeding cholesterol. The phospholipid content of all the tissues increased to a lesser extent but followed the same pattern as cholesterol with respect to time. No changes in tissue triglyceride could be detected during the experimental period. The iris had the capacity to accumulate large amounts of cholesterol. The total iridic tissue (average wet weight, 75 mg/rabbit) accumulated an average of 10.2 mg of cholesterol after the rabbit had eaten a 1% cholesterol diet for 3 months; the average increase was 14.2 mg in aortic tissue (average wet weight = 380 mg/rabbit). The severity of disease graded visually correlated with the cholesterol concentration in the cornea and aorta. Using cholesterol concentration as the criterion, no significant correlation between aortic and corneal disease was found ( P &gt;0.10), but a good degree of correlation ( P &lt;0.01) existed between the severity of iridic and aortic involvement over the 3-month experimental period.
Cognitive Function in Children and Subsequent Type 2 Diabetes
Authors: Gunilla M. Olsson, Anna-Lena Hulting, Scott M. Montgomery
Journal: Diabetes Care (2008)

To assess whether a diagnosis of type 2 diabetes by age 42 years is associated with prior cognitive deficits in childhood.Logistic regression estimated type 2 diabetes risk among 9,113 members of the 1958 British birth cohort of the National Child Development Study (NCDS). Associations with type 2 diabetes were estimated for general ability and reading comprehension assessments at age 11 years, modeled using SD units. Adjustment was for markers of early-life exposures, social and material family characteristics, sex, and disability, with further adjustment for BMI at age 7 years.Adjusted odds ratios (95% CIs) for type 2 diabetes (n = 69) are 0.67 (0.51-0.87) for general ability and 0.58 (0.44-0.77) for reading comprehension. Neither additional adjustment for BMI, nor limiting the definition of type 2 diabetes to onset after age 33 years altered the associations substantially.Impaired cognitive function may precede clinical onset of type 2 diabetes.
Erratum to: Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP
Authors: Anaïs Aulas, Stéphanie Stabile, Christine Vande Velde
Journal: Molecular Neurodegeneration (2015)

Erratum Since publication of our article [1] we have noticed that an error was introduced during the assembly of Fig. 1d (Fig. 1 here), resulting in the duplication of two panels. Specifically, lanes 7–12 probed for TIA-1 are the same as lanes 13–18 also probed for TIA-1. In addition, lanes 7–12 probed with Actin are the same as lanes 19–24 probed with Actin [1]. We sincerely regret this error. The corrected figure appears below.