tbuckley/cabot-search huggingface dataset:
Scavenger receptors target glycolipids for natural killer T cell activation
Authors: Stefan Freigang, Elise Landais, Victoria Zadorozhny, Lisa Kain, Kenji Yoshida, Yang Liu, Shenglou Deng, Wulf Palinski, Paul B. Savage, Albert Bendelac, Luc Teyton
Journal: Journal of Clinical Investigation (2012)

NKT cells are innate-like T cells with powerful regulatory functions that are a promising target for immunotherapy. The efficacy of glycolipids, such as the prototypic NKT cell antagonist α-galactosylceramide (αGalCer), is currently being evaluated in clinical trials, but little is known about factors that target lipid antigens for CD1d presentation and NKT cell activation in vivo. Lipid uptake via the LDL receptor (LDLR) has been shown for digalactosylceramide; however, whether this pathway contributes to CD1d presentation of other important NKT cell agonists remains unclear. We therefore investigated receptor-mediated uptake pathways for CD1d presentation using a panel of structurally diverse lipid antigens. We found that uptake via scavenger receptors was essential for the CD1d presentation of αGalCer and Sphingomonas glycolipids. Moreover, in vivo NKT cell responses, i.e., cytokine production, proliferation, and NKT cell help for adaptive CD4+ and CD8+ T cells, required the uptake of αGalCer via scavenger receptor A. Importantly, our data indicate that structural characteristics of glycolipids determine their receptor binding and direct individual lipids toward different uptake pathways. These results reveal an important contribution of scavenger receptors in the selection of lipids for CD1d presentation and identify structural motifs that may prove useful for therapeutic NKT cell vaccination.
Maternal Hypercholesterolemia During Pregnancy Promotes Early Atherogenesis in LDL Receptor-Deficient Mice and Alters Aortic Gene Expression Determined by Microarray
Authors: Claudio Napoli, Filomena de Nigris, John S. Welch, Federico B. Calara, Robert O. Stuart, Christopher K. Glass, Wulf Palinski
Journal: Circulation (2002)

Maternal hypercholesterolemia during pregnancy is associated with markedly enhanced fatty streak formation in human fetal aortas and accelerated progression of atherosclerosis in normocholesterolemic children.To establish the causal role of maternal hypercholesterolemia in a genetically homogeneous murine model and to test the hypothesis that pathogenic events during fetal development result in persistent changes in arterial gene expression, female LDL receptor-deficient (LDLR(-/-)) mice were fed regular chow or high-fat diets supplemented with 0.075% or 1.25% cholesterol during pregnancy. Lesion sizes were determined in the aortic origin of their chow-fed offspring at 3 months. Maternal hypercholesterolemia more than doubled lesion sizes in male offspring (P<0.0001 for the 0.0075% cholesterol group). Microarray analysis of the expression of 11 000 murine genes in the nonatherosclerotic descending aorta by Affymetrix gene chips suggested that 139 genes were significantly regulated in offspring of hypercholesterolemic mothers. A subset of 12 of the upregulated transcripts was subjected to secondary analysis by semiquantitative PCR of pooled RNA and 4 genes were found to be upregulated >1.7-fold. Quantitative PCR for one of these genes using RNA from individual mice yielded similar results. Comparative immunostaining for several of the above genes also indicated increased protein content in offspring of hypercholesterolemic mothers.These findings establish an atherogenic effect of maternal hypercholesterolemia in genetically uniform mice and indicate that changes in aortic gene expression persist long after fetal exposure to hypercholesterolemia. In addition to elucidating pathogenic mechanisms initiated during fetal development, this approach may identify genes in morphologically normal arteries that influence the susceptibility to classical risk factors of atherosclerosis.
UTMB Is 100 Years Old
Authors: Thomas N. James
Journal: JAMA (1991)

Galveston Island, home of The University of Texas Medical Branch (UTMB), lies near the northern shore of the Gulf of Mexico and has one of the world's greatest natural deep water harbors. Discovered by Spanish explorers only a few decades after Christopher Columbus landed in the New World, Galveston has been the home of shipwrecked sailors, marauding pirates (Jean Lafitte lived here), and countless numbers and varieties of migratory birds (it is, in fact, one of America's favorite sites for bird watching). From humble beginnings in a climate plagued by yellow fever and malaria, Galveston came into its own near the middle of the last century when it blossomed as a center for shipping, banking, cotton and sugar export, and related commercial activities not only for Texas, but for much of the southwest. Wise civic leaders also established it as a cultural center, and much of this legacy survives with
Responsiveness of human skin mast cells to repeated activation: an <i>in vitro</i> study
Authors: E. Rubinchik, M. Shalit, F. Levi‐Schaffer
Journal: Allergy (1998)

To assess human mast‐cell (MC) behavior after repetitive activation, we cocultured human foreskin MC (SMC) with human foreskin fibroblasts (F). Under these conditions, we have previously demonstrated that SMC keep their viability and functional activity for up to 8 days. SMC were presensitized with atopic serum and repeatedly activated by consecutively increasing concentrations of anti‐IgE antibodies (α‐IgE, 0.0002–0.1). This treatment, which mimics the “rush desensitization” procedure, led to complete SMC unresponsiveness to activation by a‐IgE at optimal concentrations, as evaluated by histamine release. However, presensitization of SMC with IgE antibodies before exposure to α‐IgE restored their sensitivity to this stimulus. These data indicate that desensitization was probably due to lack of membrane‐bound IgE rather than to downregulation of intracellular mechanisms. In fact, SMC challenged by an optimal concentration of α‐lgE could release histamine upon a second activation by 2 h after the first activation, if the cells had been presensitized before the second challenge. SMC incubation with increasing concentrations of compound 48/80 (0.2–10μg/ml) led to MC unresponsiveness to an optimal concentration of this stimulus. Furthermore, SMC activated by an optimal concentration of compound 48/80 and rechallenged with the same agent were insensitive to the second activation for at least 24 h. In summary, we have shown that it is possible to induce “desensitization” in SMC to both IgEdependent and IgE‐independent stimuli by incubating the cultures with consecutively increasing concentrations of the activator. SMC can release histamine when reactivated with a‐IgE antibodies after presensitization by 2 h after the first challenge, while they reacquire their susceptibility to reactivation with compound 48/80 in only 2–3 days.
Intratumoral Vaccination and Diversified Subcutaneous/ Intratumoral Vaccination with Recombinant Poxviruses Encoding a Tumor Antigen and Multiple Costimulatory Molecules
Authors: Chie Kudo-Saito, Jeffrey Schlom, James W. Hodge
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Intratumoral (i.t.) vaccination represents a potential modality for the therapy of tumors. Previous i.t. vaccination studies have focused on the efficacy of i.t. vaccination alone. There are no reports that clearly compared i.t. vaccination with systemic vaccination achieved by s.c., intradermal, or i.m. injection, or combining both modalities of systemic and i.t. vaccination. Here, we compared the antitumor effects induced by a systemic vaccination regimen (s.c.) and i.t. vaccination, and a sequential s.c/i.t. vaccination regimen. In this study, we used a recombinant vaccinia virus containing the transgenes for carcinoembryonic antigen (CEA) and a triad of T-cell costimulatory molecules (B7–1, ICAM-1, and LFA-3; designated rV-CEA/TRICOM) for s.c. priming and a replication defective avipox (fowlpox) virus containing the same four transgenes (designated rF-CEA/TRICOM) for i.t. vaccination or s.c. booster vaccinations. Experimental Design: Vaccination was started on day 8 after s.c. implantation with CEA-positive tumors. We compared the antitumor activity induced by these vaccines when administered via the i.t. route versus the s.c. route. Subsequent therapy studies examined the sequential combination of these routes, s.c. priming with rV-CEA/TRICOM followed by i.t. boosting with rF-CEA/TRICOM. Initial studies were conducted in conventional mice to define optimal vaccine regimens and then in CEA-transgenic mice that expressed CEA as a “self” antigen in a manner similar to that of an advanced colorectal cancer patient. Results: The results demonstrate that the antitumor activity induced by i.t. vaccination is superior to that induced by s.c. vaccination. For more advanced tumors, a s.c. priming vaccination, followed by i.t. boosting vaccinations was superior to either s.c. or i.t. vaccination alone. Both of these phenomena were observed in tumor models where the tumor-associated antigen is a foreign antigen and in a CEA-transgenic tumor model where the tumor-associated antigen is a self-antigen. The cytokine, granulocyte macrophage colony-stimulating factor admixed in vaccines, was shown to be essential in inducing the antitumor activity. Conclusions: These studies demonstrate that the diversified vaccine regimens that consisted of s.c. prime and i.t. boosts with CEA/TRICOM vectors could induce antitumor therapy superior to that seen by either route alone.
1197 Incidence, risk factors and treatment of mood disorders associated with peginterferon and ribavirin therapy in patients with chronic hepatitis C: results of a prospective study
Authors: L CASTERA, A CONSTANT, C HENRY, P CHAMPBENOIT, G SAUVE, V DELEDINGHEN, P BERNARD, J FOUCHER, J DEMOTESMAINARD, P COUZIGOU
Journal: Hepatology (2003)
Oral Contraceptives and Endometrial Cancer
Authors: Philip Cole
Journal: New England Journal of Medicine (1980)

The exemplary study of Weiss and Sayvetz of the risk of endometrial cancer among oral contraceptive (OC) users is reported. The only study limitation is that the cases available were too few to provide highly precise estimates of all the associations seen. Yet the study did show that women who took the sequential drug Oracon have a risk of endometrial cancer that is appreciably higher than that of women who did not take OCs. The study also provides some evidence that the combined drugs do not increase the risk of endometrial cancer and that they might actually be protective. The study can only suggest that other sequential drugs are not as harmful as Oracon and that they may even be protective like the combined drugs. Oracon differed from all other OCs in 3 ways, and each contributed to making it the most estrogenic: 1) only Oracon used the weak progestogen dimethisterone; 2) only Oracon supplied 100 mg daily of the estrogen ethinyl estradiol; and 3) Oracon's monthly sequence included 16 days of estrogen alone while other sequential drugs included 14 or 15 days, and the combined OCs have no estrogen-only day. The finding of Weiss and Sayvets that, if accurate, will prove to be of greatest importance is the apparent anticarcinogenic effect of combined oral contraceptives.
Brief Communication: The Relationship between Having a Living Will and Dying in Place
Authors: Howard B. Degenholtz, YongJoo Rhee, Robert M. Arnold
Journal: Annals of Internal Medicine (2004)

Background: Living wills, a type of advance directive, are promoted as a way for patients to document preferences for life-sustaining treatments should they become incompetent. Previous research, however, has found that these documents do not guide decision making in the hospital. Objective: To test the hypothesis that people with living wills are less likely to die in a hospital than in their residence before death. Design: Secondary analysis of data from a nationally representative longitudinal study. Setting: Publicly available data from the Asset and Health Dynamics Among the Oldest Old (AHEAD) study. Patients: People older than 70 years of age living in the community in 1993 who died between 1993 and 1995. Measurements: Self-report and proxy informant interviews conducted in 1993 and 1995. Results: Having a living will was associated with lower probability of dying in a hospital for nursing home residents and people living in the community. For people living in the community, the probability of in-hospital death decreased from 0.65 (95% CI, 0.58 to 0.71) to 0.52 (CI, 0.42 to 0.62). For people living in nursing homes, the probability of in-hospital death decreased from 0.35 (CI, 0.23 to 0.49) to 0.13 (CI, 0.07 to 0.22). Limitations: Retrospective survey data do not contain detailed clinical information on whether the living will was consulted. Conclusion: Living wills are associated with dying in place rather than in a hospital. This implies that previous research examining only people who died in a hospital suffers from selection bias. During advance care planning, physicians should discuss patients' preferences for location of death.
Alexithymia, Depression and Social Support among Japanese Workers
Authors: Masayo Kojima, Yoshihiro Senda, Teruo Nagaya, Shinkan Tokudome, Toshiaki A. Furukawa
Journal: Psychotherapy and Psychosomatics (2003)

&lt;i&gt;Background:&lt;/i&gt; A number of studies have shown that social support has a direct beneficial effect on well-being and also serves as a buffer to protect people from health problems due to excessive stress. Although preliminary studies report a positive relationship of alexithymia both with depression and reduced social support, there is no study examining whether the beneficial effect of social support on depression differs with the presence of alexithymia. &lt;i&gt;Methods:&lt;/i&gt; A total of 120 workers aged 19–39 completed the 20-item Toronto Alexithymia Scale (TAS-20) to measure alexithymia, the Beck Depression Inventory-II (BDI-II) to evaluate depressive symptomatology, and the Job Content Questionnaire (JCQ) to assess job strain based on Karasek’s demand-control-support model. The interrelationship among TAS-20, BDI-II and 3 subscales of JCQ (job demand, control, and support) were examined. &lt;i&gt;Results:&lt;/i&gt; A significant association of depression with low support and high alexithymia was observed. Alexithymia was also associated with reduced support. Further, a statistically significant interaction between alexithymia and support in terms of their effect on depression was observed. Nonalexithymic individuals with low support showed a significantly higher depression score than those who received high support, while alexithymics did not differ in their depression score depending on the degree of support. Consistent results were obtained from the logistic regression analysis examining the odds ratio for depression by support by alexithymia; a significantly increased odds ratio for depression associated with low social support was observed only among nonalexithymics. &lt;i&gt;Conclusions:&lt;/i&gt; Alexithymic individuals might be unable to benefit from social support because of their cognitive deficits of emotion.
Advances Toward the Implantable Artificial Pancreas for Treatment of Diabetes
Authors: Jacob Jaremko, Otto Rorstad
Journal: Diabetes Care (1998)

Recent research on development of the implantable artificial pancreas for treatment of diabetes is reviewed, based on a Medline literature search that focused on glucose sensors, insulin pumps, and pump control systems. To achieve a closed feedback loop, a clinically applicable implantable artificial pancreas requires miniaturization and coordination of three components: an insulin pump, a blood glucose monitor, and a control system. Recent clinical studies have demonstrated that implantable insulin pumps are feasible for satisfactory control of diabetes for over a year, with the major complication being obstruction of the infusion catheter. Research on continuous glucose sensors has predominantly used the glucose-oxidase reaction or near-infrared light spectroscopy. Implantable glucose oxidase sensors have been limited by local factors causing unstable signal output, whereas optical sensors must overcome interference by substances with absorption spectra similar to glucose. Investigators have developed control algorithms in an effort to stabilize operation of the integrated artificial pancreas in the face of variations in sensor output and pump function. The ultimate goals of fully automatic glucose control by an artificial pancreas include prevention or delay of chronic complications of diabetes, lowered risk of hypoglycemia, and less patient inconvenience and discomfort than with multiple daily glucose self-tests and insulin injection. The recent developments of optical glucose sensing, radiotelemetry systems to link pump and sensor, and miniaturization and refinement of insulin pumps are significant steps toward a clinically applicable artificial pancreas.
Clinical Evaluation of 1-Hydrazinophthalazin (C-5968) in Hypertension
Authors: ROBERT L. JOHNSON, EDWARD D. FREIS, HAROLD W. SCHNAPER
Journal: Circulation (1952)

Single oral doses of 1-hydrazinophthalazine frequently lowered blood pressure particularly diastolic pressure in hypertensive patients. Prolonged therapy was less successful, apparently as a result of development of tolerance or side effects. The best long-term results were obtained when l-hydrazinophthalazine was alternated with hexamethonium.
STUDIES ON THE RELATIONSHIP OF 5-HYDROXYTRYPTAMINE AND THE ENTEROCHROMAFFIN CELL TO ANAPHYLACTIC SHOCK IN MICE
Authors: Michael D. Gershon, Leonard L. Ross
Journal: The Journal of Experimental Medicine (1962)

Protection against anaphylactic shock in mice by reserpine has been shown to be a delayed phenomenon, probably not dependent upon a direct effect of reserpine. The release and depletion of catechol amines by reserpine show little likelihood of being responsible for protection because these substances are in themselves protective against anaphylactic shock, while ß-TM 10, a drug which interferes with their release is not. Since L-α-methyl dopa and reserpine both deplete serotonin, and since both protect against anaphylactic shock, it is proposed that serotonin depletion is responsible for the protection. Enterochromaffin substance is depleted in anaphylactic shock. It is also depleted by reserpine and serotonin, both of which protect against anaphylactic shock when given prior to challenge with antigen. The amount of enterochromaffin substance seems to correlate with susceptibility to anaphylactic shock. The behavior of animals undergoing anaphylactic shock and the effect of shock on body temperature is similar to the effects on behavior and temperature of treatment with reserpine, which is known to release serotonin. The effect of monoamine oxidase inhibition on animals undergoing anaphylactic shock is also similar to the effect of monoamine oxidase inhibition on animals given reserpine. These results are consistent with the views that the release of serotonin is causally related to anaphylactic shock in mice and that serotonin is accumulated in the chromogenic material of the enterochromaffin cell.
The Oral D-Xylose Test in Healthy Infants and Children
Authors: Philip Lanzkowsky
Journal: JAMA (1963)

THE ORAL D-xylose test, based upon the determination of 5-hour urinary recovery of D-xylose ( hereinafter referred to as xylose) after a loading dose of the pentose, has been widely employed in adults as a test of absorption. Since xylose is a simple sugar, digestion is unnecessary and absorption is independent of bile, intestinal, or pancreatic secretions. Xylose is absorbed chiefly in the duodenum and proximal jejunum. The primary use of this test, therefore, is in the demonstration of malabsorption states arising from lesions involving the upper small bowel wall such as gluten-induced enteropathy. This test is simple, reproducible, inexpensive, and valuable in the investigation of malabsorption states in adults.1-3In infants and children the performance of this test presents certain practical difficulties: (1) prolonged fasting with resultant dehydration in young infants, (2) the necessity for meticulous urine collection with its difficulties in young children; and (3) the necessity, on
Apixaban reduced stroke and systemic embolism compared with aspirin in adults with AF for whom VKA therapy was unsuitable
Authors: Andrew Dunn
Journal: Annals of Internal Medicine (2011)

ACP Journal Club19 April 2011Apixaban reduced stroke and systemic embolism compared with aspirin in adults with AF for whom VKA therapy was unsuitableAndrew Dunn, MD, FACP, FHMAndrew Dunn, MD, FACP, FHMMount Sinai School of Medicine, New York, New York, USA (A.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-154-8-201104190-02003 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationConnolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806-17. https://pubmed.ncbi.nlm.nih.gov/21309657Clinical Impact RatingsGIM/FP/GP: Cardiology: Hematology: References1 Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. [PMID: 19717844] Google Scholar2 Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009;360:2066-78. [PMID: 19336502] Google Scholar3 Lopes RD, Alexander JH, Al-Khatib SM, et al. Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J. 2010;159:331-9. [PMID: 20211292] Google Scholar4 Stroke Prevention in Atrial Fibrillation Investigators. Stroke prevention in atrial fibrillation study: final results. Circulation. 1991;84:527-39. [PMID: 1860198] Google Scholar Author, Article, and Disclosure InformationAffiliations: Mount Sinai School of Medicine, New York, New York, USA (A.D.)This article was published at Annals.org on 5 April 2011. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 April 2011Volume 154, Issue 8Page: JC4-3KeywordsAtrial fibrillationHemorrhageHospitalizationsIschemic strokeSafetyStrokeVitamin K ePublished: 19 April 2011 Issue Published: 19 April 2011 CopyrightCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...