tbuckley/cabot-search huggingface dataset:
Nonredundant Roles for CD1d-restricted Natural Killer T Cells and Conventional CD4+ T Cells in the Induction of Immunoglobulin E Antibodies in Response to Interleukin 18 Treatment of Mice
Authors: Tomohiro Yoshimoto, Booki Min, Takaaki Sugimoto, Nobuki Hayashi, Yuriko Ishikawa, Yuki Sasaki, Hitomi Hata, Kazuyoshi Takeda, Ko Okumura, Luc Van Kaer, William E. Paul, Kenji Nakanishi
Journal: The Journal of Experimental Medicine (2003)

Interleukin (IL)-18 synergizes with IL-12 to promote T helper cell (Th)1 responses. Somewhat paradoxically, IL-18 administration alone strongly induces immunoglobulin (Ig)E production and allergic inflammation, indicating a role for IL-18 in the generation of Th2 responses. The ability of IL-18 to induce IgE is dependent on CD4+ T cells, IL-4, and signal transducer and activator of transcription (stat)6. Here, we show that IL-18 fails to induce IgE both in CD1d−/− mice that lack natural killer T (NKT) cells and in class II−/− mice that lack conventional CD4+ T cells. However, class II−/− mice reconstituted with conventional CD4+ T cells show the capacity to produce IgE in response to IL-18. NKT cells express high levels of IL-18 receptor (R)α chain and produce significant amounts of IL-4, IL-9, and IL-13, and induce CD40 ligand expression in response to IL-2 and IL-18 stimulation in vitro. In contrast, conventional CD4+ T cells express low levels of IL-18Rα and poorly respond to IL-2 and IL-18. Nevertheless, conventional CD4+ T cells are essential for B cell IgE responses after the administration of IL-18. These findings indicate that NKT cells might be the major source of IL-4 in response to IL-18 administration and that conventional CD4+ T cells demonstrate their helper function in the presence of NKT cells.
Nonadaptive Explanations for Signatures of Partial Selective Sweeps in Drosophila
Authors: J. M. Macpherson, J. Gonzalez, D. M. Witten, J. C. Davis, N. A. Rosenberg, A. E. Hirsh, D. A. Petrov
Journal: Molecular Biology and Evolution (2008)

A beneficial mutation that has nearly but not yet fixed in a population produces a characteristic haplotype configuration, called a partial selective sweep. Whether nonadaptive processes might generate similar haplotype configurations has not been extensively explored. Here, we consider 5 population genetic data sets taken from regions flanking high-frequency transposable elements in North American strains of Drosophila melanogaster, each of which appears to be consistent with the expectations of a partial selective sweep. We use coalescent simulations to explore whether incorporation of the species' demographic history, purifying selection against the element, or suppression of recombination caused by the element could generate putatively adaptive haplotype configurations. Whereas most of the data sets would be rejected as nonneutral under the standard neutral null model, only the data set for which there is strong external evidence in support of an adaptive transposition appears to be nonneutral under the more complex null model and in particular when demography is taken into account. High-frequency, derived mutations from a recently bottlenecked population, such as we study here, are of great interest to evolutionary genetics in the context of scans for adaptive events; we discuss the broader implications of our findings in this context.
Downregulation of IgE antibody and allergic responses in the lung by epidermal biolistic microparticle delivery
Authors: Mark Kendall, Thomas J. Mitchell, George Costigan, Mark Armitage, Jason C. Lenzo, Jennifer A. Thomas, Christophe von Garnier, Graeme R. Zosky, Debra J. Turner, Phil A. Stumbles, Peter D. Sly, Patrick G. Holt, Wayne R. Thomas
Journal: Journal of Allergy and Clinical Immunology (2005)
A study of morphological basis of corn (Zea mays L.) yield under drought stress condition using correlation and path coefficient analysis
Authors: Maryam Ashofteh Beiragi, Mohsen Ebrahimi, Khodadad Mostafavi, Mohammad Golbashy, Saied Khavari Khorasani
Journal: Journal of Clinical Oncology (2011)

In order to study the morphological basis of corn yield under normal irrigation and drought stress condition, an experiment was carried out on basis of complete randomized block design with three replications and 28 new hybrids of corn; in addition 6 commercial hybrid (as control) under normal irrigation and drought stress condition in Khorasan Razavi Agricultural Research and Natural Resources Center, Mashhad, Iran on 2009. Genotypic and phenotypic correlation coefficients and path coefficients were estimated to determine the association and direct and indirect effects of different characters on total yield. Results of analysis of variance (ANOVA) showed that in both conditions there were significant differences between all hybrids for all traits. In normal irrigation condition KSC500 hybrid and in stress condition N-11 hybrid was better than others in grain yield trait. Under stress condition, number of kernels per row had the highest correlation with grain yield, while under normal irrigation ear diameter had the highest correlation with grain yield. According to this study, kernel No./ear is more closely and significantly related with total yield. This emphasized that selection based on the characters which enhance kernel number per ear will be more effective in improving yield under drought stress condition.
	
	Key words: Corn hybrids, phenotypic correlation, genotypic correlation, drought stress, irrigation.
The ulcer and the clip: which came first?
Authors: M K Heatley
Journal: Gut (2002)

An 80 year old woman was admitted in February 1999 with a history of coffee ground vomiting over a 24 hour period. Her past medical history included renal impairment (1993), pancreatitis secondary to “sludge” in the gall bladder and endoscopic retrograde cholangiopancreatography (December 1994), open cholecystectomy (December 1995), and recently diagnosed bladder tumour (January 1999). On examination, she was pale, although well, and cardiovascularly stable. Pulse was 66 beats/min regular, blood pressure was 120/70 mm Hg, …
A Randomized Controlled Trial of Continuous Positive Airway Pressure in Mild Obstructive Sleep Apnea
Authors: MAREE BARNES, DANIELLE HOUSTON, CHRISTOPHER J. WORSNOP, ALISTER M. NEILL, IVANKA J. MYKYTYN, AMANDA KAY, JOHN TRINDER, NICHOLAS A. SAUNDERS, R. DOUGLAS McEVOY, ROBERT J. PIERCE
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

A common clinical dilemma faced by sleep physicians is in deciding the level of severity at which patients with obstructive sleep apnea (OSA) should be treated. There is particular uncertainty about the need for, and the effectiveness of, treatment in mild cases. To help define the role of nasal continuous positive airway pressure (CPAP) treatment in mild OSA we undertook a randomized controlled cross-over trial of CPAP in patients with an apnea– hypopnea index (AHI) of 5 – 30 (mean, 12.9 ± 6.3 SD). Twenty-four-hour blood pressure and neurobehavioral function were measured at baseline, after 8 wk of treatment with CPAP, and after 8 wk of treatment with an oral placebo tablet. Twenty-eight of 42 patients enrolled in the study completed both treatment arms. Baseline characteristics were not different between those who completed the study and those who did not complete the study. Patients used CPAP for a mean (SD) of 3.53 (2.13) h per night and the mean AHI on the night of CPAP implementation was 4.24 (2.9). Nasal CPAP improved self-reported symptoms of OSA, including snoring, restless sleep, daytime sleepiness, and irritability (in-house questionnaire), more than did placebo, but did not improve objective (Multiple Sleep Latency Test) or subjective (Epworth Sleepiness Scale) measures of daytime sleepiness. We found no benefit of CPAP over placebo in any tests of neurobehavioral function, generic SF-36 (36-item Short Form Medical Outcomes Survey) or sleep-specific (Functional Outcomes of Sleep Questionnaire) quality of life questionnaires, mood score (Profile of Moods States and Beck Depression Index), or 24-h blood pressure. However, the placebo tablet resulted in a significant improvement in a wide range of functional variables compared with baseline. This placebo effect may account for some of the treatment responses to CPAP observed previously in patients with mild OSA.
The Role of Incretins in Glucose Homeostasis and Diabetes Treatment
Authors: Wook Kim, Josephine M. Egan
Journal: Pharmacological Reviews (2008)

Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is secreted after eating. In this manner, as well as others to be described in this review, their final common raison d9être is to aid in disposal of the products of digestion. There are two incretins, known as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), that share many common actions in the pancreas but have distinct actions outside of the pancreas. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase 4 (DPP4). A lack of secretion of incretins or an increase in their clearance are not pathogenic factors in diabetes. However, in type 2 diabetes (T2DM), GIP no longer modulates glucose-dependent insulin secretion, even at supraphysiological (pharmacological) plasma levels, and therefore GIP incompetence is detrimental to β-cell function, especially after eating. GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion. Since 2005, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in T2DM: an incretin mimetic (exenatide, which is a potent long-acting agonist of the GLP-1 receptor) and an incretin enhancer (sitagliptin, which is a DPP4 inhibitor). Exenatide is injected subcutaneously twice daily and its use leads to lower blood glucose and higher insulin levels, especially in the fed state. There is glucose-dependency to its insulin secretory capacity, making it unlikely to cause low blood sugars (hypoglycemia). DPP4 inhibitors are orally active and they increase endogenous blood levels of active incretins, thus leading to prolonged incretin action. The elevated levels of GLP-1 are thought to be the mechanism underlying their blood glucose-lowering effects.
Correlation of Major Cytogenetic Response with a Pharmacogenetic Marker in Chronic Myeloid Leukemia Patients Treated with Imatinib (STI571)
Authors: Marlene A. Dressman, Rachel Malinowski, Lee Anne McLean, Insa Gathmann, Renaud Capdeville, Martee Hensley, Mihael H. Polymeropoulos
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Imatinib, an inhibitor of the Bcr-Abl tyrosine kinase, is indicated for the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia. We examined genotypes from patients enrolled in the International Randomized Study of IFN-α versus STI571 in an attempt to identify factors that associate with cytogenetic response. Experimental Design: Sixty-eight polymorphic loci in 26 genes were examined in a subset of 187 patients (imatinib-treated patients, n = 113; IFN + 1-β-d-arabinofuranosylcytosine-treated patients, n = 74). Correlations between genotype and major cytogenetic response (MCyR) were examined by Fisher’s exact tests. Multivariate and survival analyses were also performed. Results: A significant association between MCyR and the rs2290573 polymorphism mapped to 15q22.33 was observed in imatinib-treated patients (P = 0.00037, Bonferroni corrected P = 0.025). Individuals with a CC genotype at this locus had a MCyR rate of 52% compared with individuals with a CT or TT genotype that had a MCyR rate of 89% (odds ratio, 6.72; 95% confidence interval, 1.51–29.91). In a multivariate analysis, the rs2290573 polymorphism was significant, whereas Sokal score was not. Time to progression analysis illustrated a significant difference based on genotype for the rs2290573 polymorphism. Conclusions: A significant association was identified between the genetic polymorphism rs2290573 and MCyR in imatinib-treated patients. This polymorphism is located in the intronic sequence of a putative gene with a tyrosine kinase domain. Multivariate analysis suggests that an individual’s genotype for rs2290573 has more predictive value for MCyR than prognostic variables such as Sokal score. The clinical relevance of these results requires validation in future clinical trials.
Glycoconjugate expression in normal, metaplastic, and neoplastic human upper gastrointestinal mucosa.
Authors: C Shimamoto, W M Weinstein, C R Boland
Journal: Journal of Clinical Investigation (1987)

Glycoconjugate structure in upper gastrointestinal epithelium was studied using five lectins to determine the relationship between aberrant differentiation and glycoconjugate expression. Specimens of normal esophagus, stomach, and duodenum were examined and compared with specimens of columnar metaplasia in the esophagus (Barrett's esophagus) and specimens of adenocarcinoma of the esophagus and stomach. Specific terminal glycoconjugate structures were found for the esophagus, stomach, and duodenum. Minor differences were found between the antral and fundic gland mucosae, reflecting their respective cell populations. In biopsies of Barrett's esophagus, gastric-type columnar metaplasia expressed glycoconjugates indistinguishable from those in the normal stomach. In specialized-type columnar metaplasia, a more restricted expression of glycoconjugates was seen resembling the normal duodenum. The presence of low grade dysplasia in Barrett's esophagus associated with adenocarcinoma had no impact on glycoconjugate expression. However, a distinctive difference in glycosylation was seen in high grade dysplasia of the columnar-lined esophagus and in adenocarcinoma of the esophagus and stomach. Barrett's esophagus is a morphological mosaic in which the glycoconjugate expression resembles that seen in the normal stomach and duodenum. However, in high grade dysplasia and carcinoma, variable deletion of glycoconjugate expression can be found.
The Effect of Walking on Postprandial Glycemic Excursion in Patients With Type 1 Diabetes and Healthy People
Authors: Chinmay Manohar, James A. Levine, Debashis K. Nandy, Ahmed Saad, Chiara Dalla Man, Shelly K. McCrady-Spitzer, Rita Basu, Claudio Cobelli, Rickey E. Carter, Ananda Basu, Yogish C. Kudva
Journal: Diabetes Care (2012)

Physical activity (PA), even at low intensity, promotes health and improves hyperglycemia. However, the effect of low-intensity PA captured with accelerometery on glucose variability in healthy individuals and patients with type 1 diabetes has not been examined. Quantifying the effects of PA on glycemic variability would improve artificial endocrine pancreas (AEP) algorithms.We studied 12 healthy control subjects (five males, 37.7 ± 13.7 years of age) and 12 patients with type 1 diabetes (five males, 37.4 ± 14.2 years of age) for 88 h. Participants performed PA approximating a threefold increase over their basal metabolic rate. PA was captured using a PA-monitoring system, and interstitial fluid glucose concentrations were captured with continuous glucose monitors. In random order, one meal per day was followed by inactivity, and the other meals were followed by walking. Glucose and PA data for a total of 216 meals were analyzed from 30 min prior to meal ingestion to 270 min postmeal.In healthy subjects, the incremental glucose area under the curve was 4.5 mmol/L/270 min for meals followed by walking, whereas it was 9.6 mmol/L/270 min (P = 0.022) for meals followed by inactivity. The corresponding glucose excursions for those with type 1 diabetes were 7.5 mmol/L/270 min and 18.4 mmol/L/270 min, respectively (P < 0.001).Walking significantly impacts postprandial glucose excursions in healthy populations and in those with type 1 diabetes. AEP algorithms incorporating PA may enhance tight glycemic control end points.
Renal Vascular Reactivity in Mice
Authors: XIAOPING RUAN, MICHAEL I. OLIVERIO, THOMAS M. COFFMAN, WILLIAM J. ARENDSHORST
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The present study describes methodology and its application to evaluate renal reactivity in acute studies on anesthetized mice. Renal blood flow (RBF) was measured using an ultrasonic transit-time flowmeter and a non-cannulating V-shaped probe. An intrarenal artery injection technique established feasibility and reproducibility of studies of renal vascular reactivity to angiotensin II (AngII) in adult wild-type mice. The study also examined whether AngII would affect RBF in mice lacking AT 1A receptors due to gene targeting. Mean arterial pressure averaged 83 and 62 mmHg, respectively, in mice with and without AT 1A receptors. The RBF was similar in both groups, averaging 7 ml/min per g kidney wt. AngII injection (10-μl bolus) into the renal artery produced transient, dose-dependent, selective reductions in RBF in AT 1A knockout mice as well as wild-type mice. The response was considerably greater in mice with AT 1A receptors: 10% for 0.1 ng, 30% for 1 ng, and 45% for 5 ng AngII in control animals versus respective decreases of 6, 15, and 17% in knockout mice. In other studies, angiotensin-converting enzyme (captopril) or renin (CP-71362-14) was inhibited. During inhibition of AngII formation, renal vascular reactivity to AngII increased twofold in both groups. Coadministration of the AT 1 receptor antagonist losartan (1 to 1000 ng) elicited dose-dependent inhibition of AngII effects, with near maximum blockage of 80 to 90% in both groups of mice. The putative AT 2 receptor antagonist PD 123319 inhibited 30 to 40% of AngII-induced vasoconstriction, whereas CGP 42112 had no effect in either group. In conclusion, AngII can elicit renal vasoconstriction, albeit attenuated, in AT 1A knockout mice. The weaker RBF effects are most likely due to the absence of the AT 1A receptor. Inhibition of the response by AT 1 receptor antagonist suggests mediation by the AT 1B receptor in these animals. The residual constrictor effect observed during AT 1 receptor blockade and sensitive to PD 123319 appears to be mediated by a non-AT 1 receptor.
Does environmental endotoxin exposure prevent asthma?
Authors: J Douwes, N Pearce, D Heederik
Journal: Thorax (2002)

The evidence as to whether exposure to environmental airborne endotoxin plays a protective or an inducing role in the development of asthma is reviewed. Studies of endotoxin and atopy, endotoxin and asthma, and farming and asthma are considered and, in each instance, a distinction is made between evidence of primary causation and evidence of secondary causation. It is concluded that, although it is plausible that bacterial endotoxin may protect against the development of asthma, there is considerable reason for caution regarding this hypothesis.
Mast Cell 5-Lipoxygenase Activity Promotes Intestinal Polyposis in APCΔ468 Mice
Authors: Eric C. Cheon, Khashayarsha Khazaie, Mohammad W. Khan, Matthew J. Strouch, Seth B. Krantz, Joseph Phillips, Nichole R. Blatner, Laura M. Hix, Ming Zhang, Kristen L. Dennis, Mohammed R. Salabat, Michael Heiferman, Paul J. Grippo, Hidayatullah G. Munshi, Elias Gounaris, David J. Bentrem
Journal: Cancer Research (2011)

Arachidonic acid metabolism has been implicated in colon carcinogenesis, but the role of hematopoietic 5-lipoxygenase (5LO) that may impact tumor immunity in development of colon cancer has not been explored. Here we show that tissue-specific deletion of the 5LO gene in hematopoietic cells profoundly attenuates polyp development in the APC(Δ468) murine model of colon polyposis. In vitro analyses indicated that mast cells in particular utilized 5LO to limit proliferation of intestinal epithelial cells and to mobilize myeloid-derived suppressor cells (MDSCs). Mice lacking hemapoietic expression of 5LO exhibited reduced recruitment of MDSCs to the spleen, mesenteric lymph nodes, and primary tumor site. 5LO deficiency also reduced the activity in MDSCs of arginase-1, which is thought to be critical for MDSC function. Together, our results establish a pro-tumorigenic role of hematopoietic 5LO in the immune microenvironment and suggest 5LO inhibition as an avenue for future investigation in treatment of colorectal polyposis and cancer.
Insulin Resistance and Associated Compensatory Responses in African-American and Hispanic Children
Authors: Michael I. Goran, Richard N. Bergman, Martha L. Cruz, Richard Watanabe
Journal: Diabetes Care (2002)

OBJECTIVE—The objective of this study was to compare insulin resistance relative to body fat and the associated compensatory responses in 57 healthy children living in Los Angeles, California (14 Caucasians, 15 African-Americans, and 28 Hispanics). RESEARCH DESIGN AND METHODS—Insulin sensitivity and acute insulin response were determined by intravenous glucose tolerance test. Insulin secretion, hepatic insulin extraction, and insulin clearance were estimated by C-peptide and insulin modeling. RESULTS—Insulin sensitivity was significantly lower in Hispanics and African-Americans compared with Caucasian children, and acute insulin response was significantly higher in African-American children. No ethnic differences were noted in the first-phase secretion, but second-phase insulin secretion was significantly higher in Hispanic children than in African-American children (200 ± 53 vs. 289 ± 41 nmol/min; P = 0.03). The greater acute insulin response in African-Americans, despite lower secretion, was explained by a lower hepatic insulin extraction in African-Americans compared with Hispanics (36.6 ± 2.9 vs. 47.3 ± 2.2%; P = 0.0006). CONCLUSIONS—In conclusion, Hispanic and African-American children are more insulin resistant than Caucasian children, but the associated compensatory responses are different across ethnic groups.
Intracellular calcium homeostasis in human primary muscle cells from malignant hyperthermia-susceptible and normal individuals. Effect Of overexpression of recombinant wild-type and Arg163Cys mutated ryanodine receptors.
Authors: K Censier, A Urwyler, F Zorzato, S Treves
Journal: Journal of Clinical Investigation (1998)

Malignant hyperthermia (MH) is a hypermetabolic disease triggered by volatile anesthetics and succinylcholine in genetically predisposed individuals. Nine point mutations in the skeletal muscle ryanodine receptor (RYR) gene have so far been identified and shown to correlate with the MH-susceptible phenotype, yet direct evidence linking abnormal Ca2+ homeostasis to mutations in the RYR1 cDNA has been obtained for few mutations. In this report, we show for the first time that cultured human skeletal muscle cells derived from MH-susceptible individuals exhibit a half-maximal halothane concentration causing an increase in intracellular Ca2+ concentration which is twofold lower than that of cells derived from MH-negative individuals. We also present evidence demonstrating that overexpression of wild-type RYR1 in cells obtained from MH-susceptible individuals does not restore the MH-negative phenotype, as far as Ca2+ transients elicited by halothane are concerned; on the other hand, overexpression of a mutated RYR1 Arg163Cys Ca2+ channel in muscle cells obtained from MH-negative individuals conveys hypersensitivity to halothane. Finally, our results show that the resting Ca2+ concentration of cultured skeletal muscle cells from MH-negative and MH-susceptible individuals is not significantly different.