tbuckley/cabot-search huggingface dataset:
Cellular Dynamics Visualized in Live Cells <b> <i>in Vitro</i> </b> and <b> <i>in Vivo</i> </b> by Differential Dual-Color Nuclear-Cytoplasmic Fluorescent-Protein Expression
Authors: Norio Yamamoto, Ping Jiang, Meng Yang, Mingxu Xu, Kensuke Yamauchi, Hiroyuki Tsuchiya, Katsuro Tomita, Geoffrey M. Wahl, Abdool R. Moossa, Robert M. Hoffman
Journal: Cancer Research (2004)

Abstract We report here the genetic engineering of dual-color fluorescent cells with one color in the nucleus and the other in the cytoplasm that enables real-time nuclear-cytoplasmic dynamics to be visualized in living cells in vivo as well as in vitro. To obtain the dual-color cells, red fluorescent protein (RFP) was expressed in the cytoplasm of HT-1080 human fibrosarcoma cells, and green fluorescent protein (GFP) linked to histone H2B was expressed in the nucleus. Nuclear GFP expression enabled visualization of nuclear dynamics, whereas simultaneous cytoplasmic RFP expression enabled visualization of nuclear cytoplasmic ratios as well as simultaneous cell and nuclear shape changes. Thus, total cellular dynamics can be visualized in the living dual-color cells in real time. The parental HT-1080 and the derived dual-color clones had similar cell proliferation rates, suggesting that expression of GFP and/or RFP does not affect cell cycle progression. The cell cycle position of individual living cells was readily visualized by the nuclear-cytoplasmic ratio and nuclear morphology. Real-time induction of apoptosis was observed by nuclear size changes and progressive nuclear fragmentation. Mitotic cells were visualized by whole-body imaging after injection in the mouse ear. Common carotid artery injection of dual-color cells and a reversible skin flap enabled the external visualization of the dual-color cells in microvessels in the mouse brain where extreme elongation of the cell body as well as the nucleus occurred. Dual-color cells in various positions of the cell cycle were visualized in excised mouse lungs after tail-vein injection of the dual-color cells. In the lung, the dual-color cells were observed frequently juxtaposing their nuclei, suggesting a potential novel form of cell-cell communication. The dual-color cells thus are a useful tool for visualizing living-cell dynamics in vivo as well as in vitro. Drugs that could specifically perturb these processes can now be readily screened in real time in vivo.
HLA DRB1*15‐DPB1*05 haplotype: a susceptible gene marker for isocyanate‐induced occupational asthma?
Authors: S.‐H. Kim, H.‐B. Oh, K.‐W. Lee, E.‐S. Shin, C.‐W. Kim, C.‐S. Hong, D.‐H. Nahm, H.‐S. Park
Journal: Allergy (2006)

Background: There has been no study for evaluating the associations of human leukocyte antigen (HLA) class I and II alleles with toluene diisocyanate (TDI)‐induced asthma in an Asian population. Objective: The aim of this study was to investigate a susceptible or protective marker of HLA class I and II alleles in TDI‐induced asthma. Methods: Fifty‐five patients with TDI‐induced asthma patients (group I) showing positive responses on TDI bronchoprovocation test, 47 asymptomatic exposed subjects (group II) and 95 unexposed healthy nonatopic controls (group III) were enrolled in our study. HLA class I and II genotyping was done by the direct DNA sequencing method. Results: The allelic frequency of C*09 (15.5%) was significantly higher in group I than in group III (6.8%, P = 0.019), but this statistical significance disappeared after correction was made for multiple comparisons. On two‐locus and three‐locus haplotype analysis, the allelic frequency of HLA DRB1*15‐DPB1*05 in group I (10.6%) was significantly higher than that of group II (0%, P = 0.001) and group III (2.5%, P = 0.003). The allelic frequencies of HLA A*02‐DRB1*15, A*02‐DQB1*06, B*62‐C*09 and A*02‐DRB1*15‐DQB1*06 were significantly higher in group I (8.5%, 10.3%, 8.2% and 6.8%, respectively) than those allelic frequencies of group III (1.3%, P = 0.002; 1.6%, P = 0.001; 0.6%, P &lt; 0.0001; 0%, P &lt; 0.0001, respectively). The allelic frequencies of HLA DQB1*06‐DPB1*05 and DRB1*15‐DQB1*06‐DPB1*05 were significantly higher in group I (16.0% and 10.5%) than those in group II (2.5%, P = 0.001; 0%, P = 0.001), while the frequencies of DRB1*09‐DPB1*05 and DRB1*09‐DQB1*0303‐DPB1*05 were significantly lower in group I (0% and 0%) than those of group II (7.4%, P = 0.004; 7.5%, P = 0.004). These differences remained statistically significant even after the correction for multiple comparisons. Conclusions: The HLA haplotype DRB1*15‐DPB1*05 can be a susceptibility gene marker for the development of TDI‐induced asthma among the exposed workers in the Korean population.
Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance
Authors: Jason Miska, Midhat H. Abdulreda, Priyadharshini Devarajan, Jen Bon Lui, Jun Suzuki, Antonello Pileggi, Per-Olof Berggren, Zhibin Chen
Journal: The Journal of Experimental Medicine (2014)

Real-time imaging studies are reshaping immunological paradigms, but a visual framework is lacking for self-antigen-specific T cells at the effector phase in target tissues. To address this issue, we conducted intravital, longitudinal imaging analyses of cellular behavior in nonlymphoid target tissues to illustrate some key aspects of T cell biology. We used mouse models of T cell–mediated damage and protection of pancreatic islet grafts. Both CD4+ and CD8+ effector T (Teff) lymphocytes directly engaged target cells. Strikingly, juxtaposed β cells lacking specific antigens were not subject to bystander destruction but grew substantially in days, likely by replication. In target tissue, Foxp3+ regulatory T (Treg) cells persistently contacted Teff cells with or without involvement of CD11c+ dendritic cells, an observation conciliating with the in vitro “trademark” of Treg function, contact-dependent suppression. This study illustrates tolerance induction by contact-based immune cell interaction in target tissues and highlights potentials of tissue regeneration under antigenic incognito in inflammatory settings.
Capsaicin receptors mediate free radical-induced activation of cardiac afferent endings
Authors: H Schultz
Journal: Cardiovascular Research (1998)

Objective: The effects of capsaicin on sensory neurons are mediated by its interaction with a specific membrane receptor and opening of a non-selective cation channel. In the rat heart, capsaicin-sensitive nerve endings are known to be activated by oxygen radicals. We investigated the possibility that free oxygen radicals stimulate sensory nerve endings by acting upon the capsaicin receptor. Methods: We studied the effects of capsaicin (0.16–16.0 nmol), bradykinin (0.1–10 nmol), H2O2 (1.5–30 μmol), and xanthine+xanthine oxidase (X+XO, 1 μmol+0.03 mU) applied to the surface of the rat heart for 30 s on the activity of cardiac, capsaicin-sensitive, vagal and sympathetic afferent fibers before and after blockade of capsaicin receptors with capsazepine (200 μg/kg, i.v.), a specific antagonist for the capsaicin receptor. Results: Application of capsaicin (0.32–16.0 nmol), H2O2 (9–30 μmol), bradykinin (1–10 nmol), and X+XO increased cardiac vagal and sympathetic afferent activity. Administration of capsazepine had no effect on the baseline activity of either vagal or sympathetic cardiac afferents, but it abolished the response of the afferent fibers to all doses of capsaicin, H2O2, and X+XO tested. Capsazepine had no effect on afferent activation by bradykinin. Administration of another capsaicin receptor blocker, ruthenium red (780 μg/kg, i.v.), had similar effects. Conclusions: The results of these experiments indicate that blockade of capsaicin receptors inhibits activation of vagal and sympathetic cardiac afferent fibers by free oxygen radicals. The fact that capsazepine and ruthenium red did not affect the afferent response to bradykinin suggests that this effect of the blockers was specific for capsaicin receptors. The possible functional implications of this interaction are discussed.
Therapeutic effects on cartilage metabolism in arthritis as measured by release of proteoglycan structures into the synovial fluid.
Authors: T Saxne, D Heinegard, F A Wollheim
Journal: Annals of the Rheumatic Diseases (1986)

Proteoglycans are molecules that are degraded and released from the articular cartilage into the synovial fluid early in an arthritic process. Such released proteoglycans were quantified by an enzyme linked immunosorbent assay (ELISA). The proteoglycan content in synovial fluid from patients with various knee joint arthritides was constant in two samples withdrawn five days apart. To determine if therapeutic measures were paralleled by effects directly on the articular cartilage the patients were treated with local injections of glucocorticoids. In all patients the glucocorticoids induced a reduction of the proteoglycan content in the synovial fluid, reflecting their effects on the cartilage. In two patients with spontaneous remission of their arthritis a reduction in the proteoglycan content in the synovial fluid was also noted. The quantification of proteoglycans in synovial fluid appears to have potential as a useful tool for monitoring the effects of therapy on cartilage metabolism.
Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2
Authors: Allen J. Taylor, Lance E. Sullenberger, Hyun J. Lee, Jeannie K. Lee, Karen A. Grace
Journal: Circulation (2004)

Niacin reduces coronary heart disease morbidity and mortality when taken either alone or in combination with statins; however, the incremental impact of adding niacin to background statin therapy is unknown.This was a double-blind randomized placebo-controlled study of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease and low levels of high-density lipoprotein cholesterol (HDL-C; <45 mg/dL). The primary end point was the change in common carotid intima-media thickness (CIMT) after 1 year. Baseline CIMT (0.884+/-0.234 mm), low-density lipoprotein cholesterol (89+/-20 mg/dL), and HDL-C (40+/-7 mg/dL) were comparable in the placebo and niacin groups. Adherence to niacin exceeded 90%, and 149 patients (89.2%) completed the study. HDL-C increased 21% (39 to 47 mg/dL) in the niacin group. After 12 months, mean CIMT increased significantly in the placebo group (0.044+/-0.100 mm; P<0.001) and was unchanged in the niacin group (0.014+/-0.104 mm; P=0.23). Although the overall difference in IMT progression between the niacin and placebo groups was not statistically significant (P=0.08), niacin significantly reduced the rate of IMT progression in subjects without insulin resistance (P=0.026). Clinical cardiovascular events occurred in 3 patients treated with niacin (3.8%) and 7 patients treated with placebo (9.6%; P=0.20).The addition of extended-release niacin to statin therapy slowed the progression of atherosclerosis among individuals with known coronary heart disease and moderately low HDL-C.
ULTRASTRUCTURAL STUTDY OF THE CUTANEOUS ELASTIC FIBRES IN IN LUPUS ERYTHEMATOSUS
Authors: D. SCHMITT, J. THIVOLET, H. PERROT
Journal: British Journal of Dermatology (1972)

Summary.— During the ultrastructural study of the cutaneous lesions of 5 cases of systemic lupus erythematosus (S.L.E.) and 2 cases of discoid lupus erythematosus (D.L.E.), the authors report the changes observed in dermal elastic fibres. These changes consist in a progressive disappearance of the granular matrix and in the subsequent appearance of the fibrillar component of the elastic fibres. These modifications of which several types are described, end in the formation of fibrillar bodies. The evolution of these changes is compared to the evolution of actinic elastosis.
Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review
Authors: Yu Imamura, Paul Lochhead, Mai Yamauchi, Aya Kuchiba, Zhi Rong Qian, Xiaoyun Liao, Reiko Nishihara, Seungyoun Jung, Kana Wu, Katsuhiko Nosho, Yaoyu E Wang, Shouyong Peng, Adam J Bass, Kevin M Haigis, Jeffrey A Meyerhardt, Andrew T Chan, Charles S Fuchs, Shuji Ogino
Journal: Molecular Cancer (2014)

KRAS mutations in codons 12 and 13 are established predictive biomarkers for anti-EGFR therapy in colorectal cancer. Previous studies suggest that KRAS codon 61 and 146 mutations may also predict resistance to anti-EGFR therapy in colorectal cancer. However, clinicopathological, molecular, and prognostic features of colorectal carcinoma with KRAS codon 61 or 146 mutation remain unclear. We utilized a molecular pathological epidemiology database of 1267 colon and rectal cancers in the Nurse’s Health Study and the Health Professionals Follow-up Study. We examined KRAS mutations in codons 12, 13, 61 and 146 (assessed by pyrosequencing), in relation to clinicopathological features, and tumor molecular markers, including BRAF and PIK3CA mutations, CpG island methylator phenotype (CIMP), LINE-1 methylation, and microsatellite instability (MSI). Survival analyses were performed in 1067 BRAF-wild-type cancers to avoid confounding by BRAF mutation. Cox proportional hazards models were used to compute mortality hazard ratio, adjusting for potential confounders, including disease stage, PIK3CA mutation, CIMP, LINE-1 hypomethylation, and MSI. KRAS codon 61 mutations were detected in 19 cases (1.5%), and codon 146 mutations in 40 cases (3.2%). Overall KRAS mutation prevalence in colorectal cancers was 40% (=505/1267). Of interest, compared to KRAS-wild-type, overall, KRAS-mutated cancers more frequently exhibited cecal location (24% vs. 12% in KRAS-wild-type; P < 0.0001), CIMP-low (49% vs. 32% in KRAS-wild-type; P < 0.0001), and PIK3CA mutations (24% vs. 11% in KRAS-wild-type; P < 0.0001). These trends were evident irrespective of mutated codon, though statistical power was limited for codon 61 mutants. Neither KRAS codon 61 nor codon 146 mutation was significantly associated with clinical outcome or prognosis in univariate or multivariate analysis [colorectal cancer-specific mortality hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.29-2.26 for codon 61 mutation; colorectal cancer-specific mortality HR = 0.86, 95% CI = 0.42-1.78 for codon 146 mutation]. Tumors with KRAS mutations in codons 61 and 146 account for an appreciable proportion (approximately 5%) of colorectal cancers, and their clinicopathological and molecular features appear generally similar to KRAS codon 12 or 13 mutated cancers. To further assess clinical utility of KRAS codon 61 and 146 testing, large-scale trials are warranted.
The Origin of the Haitian Cholera Outbreak Strain
Authors: Chen-Shan Chin, Jon Sorenson, Jason B. Harris, William P. Robins, Richelle C. Charles, Roger R. Jean-Charles, James Bullard, Dale R. Webster, Andrew Kasarskis, Paul Peluso, Ellen E. Paxinos, Yoshiharu Yamaichi, Stephen B. Calderwood, John J. Mekalanos, Eric E. Schadt, Matthew K. Waldor
Journal: New England Journal of Medicine (2010)

Although cholera has been present in Latin America since 1991, it had not been epidemic in Haiti for at least 100 years. Recently, however, there has been a severe outbreak of cholera in Haiti.We used third-generation single-molecule real-time DNA sequencing to determine the genome sequences of 2 clinical Vibrio cholerae isolates from the current outbreak in Haiti, 1 strain that caused cholera in Latin America in 1991, and 2 strains isolated in South Asia in 2002 and 2008. Using primary sequence data, we compared the genomes of these 5 strains and a set of previously obtained partial genomic sequences of 23 diverse strains of V. cholerae to assess the likely origin of the cholera outbreak in Haiti.Both single-nucleotide variations and the presence and structure of hypervariable chromosomal elements indicate that there is a close relationship between the Haitian isolates and variant V. cholerae El Tor O1 strains isolated in Bangladesh in 2002 and 2008. In contrast, analysis of genomic variation of the Haitian isolates reveals a more distant relationship with circulating South American isolates.The Haitian epidemic is probably the result of the introduction, through human activity, of a V. cholerae strain from a distant geographic source. (Funded by the National Institute of Allergy and Infectious Diseases and the Howard Hughes Medical Institute.).
Manometric measurement of human sphincter of Oddi length.
Authors: F I Habib, E Corazziari, D Biliotti, L Primerano, A Viscardi, V Speranza, E De Masi, G Fegiz, A Torsoli
Journal: Gut (1988)

Length of biliary (CBD) and/or pancreatic (PD) sphincter of Oddi (SO) was measured during perendoscopic or intraoperative manometry in 21 control subjects and in 46 patients with biliary disease. When the high resting pressure (HPZ) and the phasic wave zone (PAZ) were considered, SO length was, in the control group, 9.5 +/- 0.5 mm (M +/- SE) and 9.4 +/- 0.6 mm at the level of the CBD-SO, and 7.7 +/- 0.6 mm and 6.9 +/- 0.5 mm at the level of the PD-SO. The physiological sphincter length appeared substantially shorter than the anatomical one, as reported in the literature. No significant differences were found between controls and patients with CBD stones. Endoscopic sphincterotomy without manometry reduced mean sphincter length length of the sphincterotomy was tailored to the manometric findings. Surgical partial sphincterotomy reduced sphincter length by only 46.7 +/- 10.3%.
Chest radiotherapy to achieve lung volume reduction
Authors: J.A. Murray, J. Lyons
Journal: European Respiratory Journal (2012)

we also investigated inflammatory local and systemic cytokine profiles and clinical resolution of infectious parameters.In fact, our results clearly show that neutrophil apoptosis is associated with lower proinflammatory cytokine levels and faster clinical stability.This is a finding that would probably not have been changed if we had obtained lung biopsies.Another comment refers to transepithelial elimination of neutrophils during resolution of NCAP.The interesting proposed hypothesis of inflammatory resolution through egression of leukocytes is very attractive [3].C.G.A. Persson and L. Uller argue that elimination of leukocytes from the airways with bronchial inflammation (transepithelial egression) is a mode of resolving inflammation.This challenging interpretation is nicely presented in human and animal models in asthma and chronic obstructive pulmonary disease.However in pneumonia, the acute inflammatory response of host against microorganisms is a completely different model of airway inflammation.In pneumonia, innate responses and alveolar macrophages orchestrate the inflammatory response in lung parenchyma, and neutrophils exit the pulmonary circulation at the capillary level, that is, mainly in alveolar air spaces.Obviously, our design was not directed to evaluate the neutrophil migration across the alveolar or epithelial lining, although this topic merits attention.Referring to the comments that evidence of neutrophil apoptosis in inflammation resolution is not very strong, it is worth mentioning that our results and those from other researchers seem to indicate the contrary [4-6].We have found a significant correlation between neutrophil apoptosis and pneumonia outcome.Our results agree with the comment made by , indicating that studies in humans suggest that neutrophil apoptosis is inhibited early in acute respiratory distress syndrome but returns to normal as inflammation resolves.These authors also indicate other steps that must be explored to understand all the process, but they were not the objective of our present work.DROEMANN et al. [8] have results in concordance with ours, and the differences in the rate of neutrophil apoptosis are probably due to the initial phase of pneumonia (24 h).So, we consider that the study of cytokine patterns and neutrophil apoptosis in BAL fluid from NACP is currently an excellent available option to evaluate the ongoing inflammatory process ex vivo.With regard to the role of the transepithelial exit of leukocytes from the airway proposed by C.G.A. Persson and L. Uller for asthma and chronic obstructive pulmonary disease, it should not be directly translated to pneumonia, an acute infection with a completely different restitutio in integrum.Finally, we totally agree that regarding the host response against microorganisms and resolution of inflammation, there are still many missing important pieces and new approaches are welcome.
A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase.
Authors: M E Morrison, S Vijayasaradhi, D Engelstein, A P Albino, A N Houghton
Journal: The Journal of Experimental Medicine (1993)

Adenosine deaminase binding protein (ADAbp) is a cell surface glycoprotein that is expressed by normal melanocytes but not by melanoma, the malignant counterpart. ADAbp is specifically downregulated during malignant transformation of melanocytes. Recently, we have developed a system that progressively transforms melanocytes in vitro in defined steps. Transduction with v-Ha-ras oncogene followed by long-term culture leads to a cell phenotype and genotype that specifically mimics human melanoma. Loss of ADAbp expression occurred concomitantly with the emergence of growth factor independence and appearance of specific chromosomal abnormalities. The cellular function of ADAbp has not been defined. To characterize ADAbp, the mature 110-kD form was purified from human kidney. Five tryptic peptides from purified human ADAbp revealed 100% homology to a serine protease, human dipeptidyl peptidase IV (DPP IV), also known as CD26. DPP IV activity was detected in lysates from human melanocytes and renal carcinoma cells but not melanoma cells, and DPP IV activity could be specifically isolated from melanocytes by binding to ADA or to S27 monoclonal antibody against ADAbp. These findings show that ADAbp is a cell surface ectopeptidase that is tightly regulated during neoplastic transformation of melanocytes.
B-Type Natriuretic Peptide Testing, Clinical Outcomes, and Health Services Use in Emergency Department Patients With Dyspnea
Authors: Hans-Gerhard Schneider
Journal: Annals of Internal Medicine (2009)

Background: B-type natriuretic peptide (BNP) is used to diagnose heart failure, but the effects of using the test on all dyspneic patients is uncertain. Objective: To assess whether BNP testing alters clinical outcomes and health services use of acutely dyspneic patients. Design: Randomized, single-blind study. Patients were assigned to a treatment group through randomized numbers in a sealed envelope. Patients were blinded to the intervention, but clinicians and those who assessed trial outcomes were not. Setting: 2 Australian teaching hospital emergency departments. Patients: 612 consecutive patients who presented with acute severe dyspnea from August 2005 to March 2007. Intervention: BNP testing (n = 306) or no testing (n = 306). Measurements: Admission rates, length of stay, and emergency department medications (primary outcomes); mortality and readmission rates (secondary outcomes). Results: There were no between-group differences in hospital admission rates (85.6% [BNP group] vs. 86.6% [control group]; difference, −1.0 percentage point [95% CI, −6.5 to 4.5 percentage points]; P = 0.73), length of admission (median, 4.4 days [interquartile range, 2 to 9 days] vs. 5.0 days [interquartile range, 2 to 9 days]; P = 0.94), or management of patients in the emergency department. Test discrimination was good (area under the receiver-operating characteristic curve, 0.87 [CI, 0.83 to 0.91]). Adverse events were not measured. Limitation: Most patients were very short of breath and required hospitalization; the findings might not apply for evaluating patients with milder degrees of breathlessness. Conclusion: Measurement of BNP in all emergency department patients with severe shortness of breath had no apparent effects on clinical outcomes or use of health services. The findings do not support routine use of BNP testing in all severely dyspneic patients in the emergency department. Primary Funding Source: Janssen-Cilag.