tbuckley/cabot-search huggingface dataset:
Metabolism and Circadian Rhythms—Implications for Obesity
Authors: Oren Froy
Journal: Endocrine Reviews (2009)

Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Human homeostatic systems have adapted to daily changes in light and dark in a way that the body anticipates the sleep and activity periods. Mammals have developed an endogenous circadian clock located in the suprachiasmatic nuclei of the anterior hypothalamus that responds to the environmental light-dark cycle. Similar clocks have been found in peripheral tissues, such as the liver, intestine, and adipose tissue, regulating cellular and physiological functions. The circadian clock has been reported to regulate metabolism and energy homeostasis in the liver and other peripheral tissues. This is achieved by mediating the expression and/or activity of certain metabolic enzymes and transport systems. In return, key metabolic enzymes and transcription activators interact with and affect the core clock mechanism. In addition, the core clock mechanism has been shown to be linked with lipogenic and adipogenic pathways. Animals with mutations in clock genes that disrupt cellular rhythmicity have provided evidence for the relationship between the circadian clock and metabolic homeostasis. In addition, clinical studies in shift workers and obese patients accentuate the link between the circadian clock and metabolism. This review will focus on the interconnection between the circadian clock and metabolism, with implications for obesity and how the circadian clock is influenced by hormones, nutrients, and timed meals.
Immunologically nonspecific mechanisms of tissue destruction in the rejection of skin grafts.
Authors: D P Doody, K S Stenger, H J Winn
Journal: The Journal of Experimental Medicine (1994)

When mice are lethally irradiated and reconstituted with allogeneic bone marrow cells, their skin is repopulated over a period of several months with Langerhans cells (LC) of marrow donor origin. Skin from such mice, when transplanted to unirradiated syngeneic recipients, became in many cases the sites of intense inflammatory responses that led to varying degrees of destruction of the transplanted skin and in some instances, to rejection of the entire graft. The frequency and intensity of these responses were influenced by the nature of the immunogenetic disparity between the donors and recipients of the marrow cells. Chimeric skin placed on hybrid mice derived from crosses between the marrow donors and recipients behaved in all respects as syngeneic grafts or autografts. When the recipients of the chimeric skin were presensitized to the antigens of the marrow donor, the responses were especially intense, and resulted in all cases in complete rejection. Thus the immunologically mediated attack on the allogeneic LCs was accompanied by widespread and nonspecific destruction of bystander cells. In all cases, the inflammation and tissue damage were confined sharply to the grafted skin, showing clearly that nonspecific or indirect tissue destruction is entirely consistent with highly selective destruction of grafted tissues. This finding removes a major objection to postulated mechanisms of rejection that involve indirect destruction of grafted tissues.
Marantic Valvular Vegetations
Authors: BRUCE F. WALLER, WILLIAM S. KNAPP, JESSE E. EDWARDS
Journal: Circulation (1973)

Marantic valvular vegetations represent one form of vegetative nonbacterial endocarditis. While any of the cardiac valves may be involved, the mitral valve and/or aortic valve are the most common sites at which this process occurs. Underlying disease of a chronic nature is usually identifiable somewhere in the body, with malignant tumors collectively representing the most common underlying condition. Systemic arterial occlusion, usually multiple when present, may antedate the identification of an underlying malignant tumor. The gross nature of the vegetations requires histologic distinction from metastatic lesions of valves and from bacterial endocarditis. In some instances, the latter process may originate upon marantic vegetations.
Hydrogen peroxide regulation of endothelial function: Origins, mechanisms, and consequences
Authors: H CAI
Journal: Cardiovascular Research (2005)

Increased production of reactive oxygen species (ROS) has been implicated in the pathogenesis of cardiovascular diseases. Enzymatic systems such as the mitochondrial respiratory chain, vascular NAD(P)H oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase (eNOS) produce superoxide anion (O2.−) in vascular cells. While some O2.− rapidly degrades by reacting with nitric oxide (NO.), the O2.− signal preserved by dismutation into hydrogen peroxide (H2O2) exerts prolonged signaling effects. This review focuses on patterns and mechanisms whereby H2O2 modulates different aspects of endothelial cell function including endothelial cell growth and proliferation, endothelial apoptosis, endothelium-dependent vasorelaxation, endothelial cytoskeletal reorganization and barrier dysfunction, endothelial inflammatory responses, and endothelium-regulated vascular remodeling. These modulations of endothelial cell function may at least partially underlie H2O2 contribution to the development of vascular disease.
Mechanism of myocardial injury in dogs with hypokalaemia
Authors: S. SUGIYAMA, T. TAKAMURA, M. AJIOKA, S. NAGAI, T. OZAWA
Journal: Cardiovascular Research (1988)

Hypokalaemia was induced by infusing polystyrene sulphonate into the colon of mongrel dogs. Sixty minutes after infusion adrenaline 10 μg·kg−1 was injected intravenously, which had no effect on serum creatine kinase activity or myocardial histology in the control dogs. However, in dogs with hypokalaemia creatine kinase activity was increased, and pronounced histological changes were seen 60 min after injection. A clear reciprocal relation was found between serum potassium concentration and creatine kinase activity. Premedication with an alpha1 blocking agent prevented the changes associated with hypokalaemia. Heart mitochondria were prepared from other dogs with hypokalaemia 5 min after adrenaline injection and their calcium content measured. Heart mitochondrial calcium content was increased in parallel with the decrease in serum potassium concentration. Alpha1 blockade also prevented the increase in mitochondrial calcium content. These results indicate that the intracellular calcium concentration is considerably increased by alpha1 receptor stimulus under hypokalaemic conditions and that this increase in calcium concentration plays a crucial role in the genesis of myocardial damage. Since adrenaline increases coronary blood flow small doses of adrenaline in subjects with hypokalaemia may lead to the development of myocardial injury not associated with ischaemia.
The Transplant Patient: Biological, Psychiatric, and Ethical Issues in Organ Transplantation
Authors: James Westphal
Journal: Annals of Internal Medicine (2001)

Medical Writings: Book Notes3 April 2001The Transplant Patient: Biological, Psychiatric, and Ethical Issues in Organ TransplantationJames Westphal, MDJames Westphal, MDConsultation/Liaison Psychiatry, Louisiana State University Health Sciences Center, Shreveport, Louisiana. (Westphal)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-7-200104030-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Trzepacz PT, DiMartini AF, eds. 311 pages. New York: Cambridge Univ Pr; 2000. $64.95. ISBN 0521553547. Order phone 800-872-7423.Field of medicine: Transplantation medicine.Format: Hardcover book.Audience: Physicians who select, manage, and advise patients undergoing transplantation and their families.Purpose: To review the psychosocial, psychiatric, and ethical aspects of organ transplantation.Content: The book focuses on the psychosocial aspects of the selection of candidates for transplantation and living organ donation, the quality of life of transplant recipients, cognitive assessment of transplantation candidates, and special issues in the psychopharmacologic treatment of transplant recipients.Highlights: The chapters on quality of life ... Author, Article, and Disclosure InformationAffiliations: Consultation/Liaison Psychiatry, Louisiana State University Health Sciences Center, Shreveport, Louisiana. (Westphal) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCentral importance of emotional and quality-of-life outcomes in the public’s perception of face transplantation 3 April 2001Volume 134, Issue 7Page: 628KeywordsCancer geneticsLiver transplantationOrgan transplantationPharmacokineticsPsychopharmacologyQuality of lifeResearch quality assessmentSoftware toolsStandardized testsTransplantation ePublished: 3 April 2001 Issue Published: 3 April 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Phospholipid exchange between plasma and erythrocytes in man and the dog
Authors: Claude F. Reed
Journal: Journal of Clinical Investigation (1968)

The turnover of the four major erythrocyte phospholipids has been studied with 32P, both in vivo and in vitro, in man and the dog. Phosphatidyl serine and phosphatidyl ethanolamine appeared to be stable erythrocyte lipids in both species. Turnover of the phosphate moiety of lecithin and sphingomyelin in the circulating erythrocytes of these two species seems entirely due to an exchange of the whole molecule with the corresponding plasma compound. Exchangeable and nonexchangeable pools of these two cellular lipids were found. In man about 60% of erythrocyte lecithin is exchangeable. The 12 hr fractional turnover of this pool is approximately 13%. Only 30% of the sphingomyelin in human cells appeared exchangeable; this portion had a 12 hr fractional turnover of about 14%. Similar results were obtained in the dog except that in this species about 75% of the erythrocyte sphingomyelin was exchangeable. Inorganic 32P was not incorporated into any of the four major phospholipids in either species. The present findings aid in estimating quantitatively the effect of plasmaerythrocyte lipid exchange on red blood cell phospholipids.
243 ALBUMIN FOR ACUTE EPISODIC HEPATIC ENCEPHALOPATHY (ALFAE STUDY)
Authors: M. Simón-Talero, R. García-Martínez, M. Torrens, G. Pereira, M. Guevara, E. Roman, G. Soriano, J. Sánchez-Delgado, J. Córdoba
Journal: Journal of Hepatology (2013)
Leishmania braziliensis braziliensis infection of the nipple.
Authors: P D Marsden, E A Almeida, E A Llanos-Cuentas, J L Costa, A V Megalhaes, N E Peterson, C C Cuba, A C Barreto
Journal: BMJ (1985)

3 observations de cette lesion rare: au niveau du mamelon chez un homme de 37 ans, en plusieurs localisations chez une jeune femme allaitant, y compris un mamelon, et au niveau de la levre chez le nourrisson de 3 mois. Excision de granulomes (histologiquement benins). Traitement efficace de la mere et du nourrisson par antimonate de meglumine
Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells
Authors: S Geyh, S Öz, R-P Cadeddu, J Fröbel, B Brückner, A Kündgen, R Fenk, I Bruns, C Zilkens, D Hermsen, N Gattermann, G Kobbe, U Germing, F Lyko, R Haas, T Schroeder
Journal: Leukemia (2013)
Food webs: reconciling the structure and function of biodiversity
Authors: Ross M. Thompson, Ulrich Brose, Jennifer A. Dunne, Robert O. Hall, Sally Hladyz, Roger L. Kitching, Neo D. Martinez, Heidi Rantala, Tamara N. Romanuk, Daniel B. Stouffer, Jason M. Tylianakis
Journal: Trends in Ecology & Evolution (2012)
Abstract 4595: Activating mutations in the <i>NT5C2</i> nucleotidase gene drive chemotherapy resistance in relapsed ALL.
Authors: Gannie Tzoneva, Arianne Perez-Garcia, Zachary Carpenter, Hossein Khiabanian, Valeria Tosello, Maddalena Allegretta, Elisabeth Paietta, Janis Racevkis, Jakob M. Rowe, Martin S. Tallman, Maddalena Paganin, Jana Hoff, Renate Kirschner-Schwabe, Teresa Palomero, Raul Rabadan, Adolfo Ferrando
Journal: Cancer Research (2013)

Abstract Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Despite intensive chemotherapy, 20% of pediatric and over 50% of adult ALL patients fail to achieve a complete remission or relapse after intensified chemotherapy, making disease relapse and resistance to therapy the most significant challenge in the treatment of this disease. Using whole exome sequencing, here we identify mutations in NT5C2, a 5’-nucleotidase enzyme responsible for inactivation of nucleoside analog chemotherapy drugs, in 20/103 (19%) relapse T-ALLs and in 1/35 (3%) relapse B-precursor ALLs analyzed. NT5C2 mutant proteins show increased nucleotidase activity in vitro and conferred resistance to chemotherapy with 6-mercaptopurine and 6-thioguanine when expressed in ALL lymphoblasts. These results support a prominent role for activating mutations in NT5C2 and increased nucleoside analog metabolism in disease progression and chemotherapy resistance in ALL. Citation Format: Gannie Tzoneva, Arianne Perez-Garcia, Zachary Carpenter, Hossein Khiabanian, Valeria Tosello, Maddalena Allegretta, Elisabeth Paietta, Janis Racevkis, Jakob M. Rowe, Martin S. Tallman, Maddalena Paganin, Jana Hoff, Renate Kirschner-Schwabe, Teresa Palomero, Raul Rabadan, Adolfo Ferrando. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4595. doi:10.1158/1538-7445.AM2013-4595
P45 Sputum And Nasal Markers Of Inflammation In Severe Asthma - A Pilot Study
Authors: G. Tavernier, R. Niven
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> The Manchester Severe Asthma Team has successfully been using sputum eosinophil monitoring for several years to help tailor steroid medication. Whilst very useful for patients able to produce a sputum sample, some patients cannot produce a sample. As a result we looked at developing an alternative method of monitoring using nasal lavage samples to study the intra-individual changes in inflammation in severe asthma. <h3>Methods</h3> Patients requiring sputum monitoring as part of their clinical management were invited to take part in this pilot and to provide an additional nasal lavage sample obtained using an olive method. Participants were clear of infection at time of sampling. Sputum was either spontaneous or induced using the traditional 3%-4%-5% nebulised sodium chloride procedure. ECP (Eosinophil Cationic Protein) was measured in sputum and nasal supernatants using a commercial ELISA kit (Mesacup, MBL). Differential cell count (DCC) was attempted for both sputum and nasal sample types. <h3>Results</h3> This abstract show the results obtained for the first 32 consecutive patients. Our patient population is described in Table 1, 69% female, 69% atopic (as defined by positive RAST of elevated total IgE), and 50% were non-smokers, 7.6 current smokers and 42.4% ex-smokers. No patient was immunosuppressed or on IM Triamcinolone. ECP levels were as follows: Sputum: median 2650 (min:20.76–28603 ng/ml), 100% of samples had detectable levels. Nasal lavage: 0(0–7.6), 20%. DCC were as follows: Sputum: 38% patients were eosinophil positive (as defined by &gt;3%), Nasal lavage: no eosinophil was detected, 38.5% of samples had a DCC but interpretation was hindered by low cell yield. Sputum DCC/ECP did not correlate significantly with nasal ECP (Pearson R=0.168, p = 0.374 and R=-0.048, p = 0.807 respectively). Nasal DCC data could not be computed as no patient was found to be eosinophil positive. Sputum DTT and sputum ECP correlated significantly (Pearson R=0.607, p = 0.001) as reported in the literature. <h3>Conclusions</h3> At this stage of our pilot, intermediate data analysis shows that nasal sampling does not appear to be a successful alternative to sputum monitoring in severe asthma.
Characterization of cell types during rat liver development
Authors: Henning C. Fiegel, Jonas J. H. Park, Michael V. Lioznov, Andreas Martin, Stefan Jaeschke-Melli, Peter M. Kaufmann, Boris Fehse, Axel R. Zander, Dietrich Kluth
Journal: Hepatology (2003)

Hepatic stem cells have been identified in adult liver. Recently, the origin of hepatic progenitors and hepatocytes from bone marrow was demonstrated. Hematopoietic and hepatic stem cells share the markers CD 34, c-kit, and Thy1. Little is known about liver stem cells during liver development. In this study, we investigated the potential stem cell marker Thy1 and hepatocytic marker CK-18 during liver development to identify putative fetal liver stem cell candidates. Livers were harvested from embryonic and fetal day (ED) 16, ED 18, ED 20, and neonatal ED 22 stage rat fetuses from Sprague-Dawley rats. Fetal livers were digested by collagenase-DNAse solution and purified by percoll centrifugation. Magnetic cell sorting (MACS) depletion of fetal liver cells was performed using OX43 and OX44 antibodies. Cells were characterized by immunocytochemistry for Thy1, CK-18, and proliferating cell antigen Ki-67 and double labeling for Thy1 and CK-18. Thy1 expression was found at all stages of liver development before and after MACS in immunocytochemistry. Thy1 positive cells were enriched after MACS only in early developmental stages. An enrichment of CK-18 positive cells was found after MACS at all developmental stages. Cells coexpressing Thy1 and CK-18 were identified by double labeling of fetal liver cell isolates. In conclusion, hepatic progenitor cells (CK-18 positive) in fetal rat liver express Thy1. Other progenitors express only CK-18. This indicates the coexistence of different hepatic cell compartments. Isolation and further characterization of such cells is needed to demonstrate their biologic properties.
Zoledronic Acid Reduces Bone Loss and Tumor Growth in an Orthotopic Xenograft Model of Osteolytic Oral Squamous Cell Carcinoma
Authors: Chelsea K. Martin, Jillian L. Werbeck, Nanda K. Thudi, Lisa G. Lanigan, Tobie D. Wolfe, Ramiro E. Toribio, Thomas J. Rosol
Journal: Cancer Research (2010)

Squamous cell carcinoma (SCC) is the most common form of oral cancer. Destruction and invasion of mandibular and maxillary bone frequently occurs and contributes to morbidity and mortality. We hypothesized that the bisphosphonate drug zoledronic acid (ZOL) would inhibit tumor-induced osteolysis and reduce tumor growth and invasion in a murine xenograft model of bone-invasive oral SCC (OSCC) derived from an osteolytic feline OSCC. Luciferase-expressing OSCC cells (SCCF2Luc) were injected into the perimaxillary subgingiva of nude mice, which were then treated with 100 μg/kg ZOL or vehicle. ZOL treatment reduced tumor growth and prevented loss of bone volume and surface area but had no effect on tumor invasion. Effects on bone were associated with reduced osteolysis and increased periosteal new bone formation. ZOL-mediated inhibition of tumor-induced osteolysis was characterized by reduced numbers of tartrate-resistant acid phosphatase-positive osteoclasts at the tumor-bone interface, where it was associated with osteoclast vacuolar degeneration. The ratio of eroded to total bone surface was not affected by treatment, arguing that ZOL-mediated inhibition of osteolysis was independent of effects on osteoclast activation or initiation of bone resorption. In summary, our results establish that ZOL can reduce OSCC-induced osteolysis and may be valuable as an adjuvant therapy in OSCC to preserve mandibular and maxillary bone volume and function.
George S. Eisenbarth: Insulin and Type 1 Diabetes
Authors: Alberto Pugliese, Jay S. Skyler
Journal: Diabetes Care (2013)

George S. Eisenbarth, MD, PhD, could be considered a natural conduit in the research of type 1 diabetes (T1D) and the fields of endocrinology and immunology. His recognition of T1D as a chronic autoimmune disease has advanced the field toward prediction, prevention, and clinical trials. His focus on insulin as the key autoantigen in islet autoimmunity unraveled the molecular basis of the insulin autoimmune response, leading to experimental antigen-specific therapies that are presently approaching clinical translation and represent a model approach for the treatment of human T1D and other autoimmune diseases.

George Eisenbarth was born in 1947, in Brooklyn, New York, to a working-class family of German ancestry. He graduated from Grover Cleveland High School in 1965 and won a Pulitzer Scholarship to Columbia University in New York City. His father feared the scholarship was some sort of scam that would not fully cover tuition, and he had to be convinced to let Eisenbarth enter the program. Eisenbarth obtained a BA degree from Columbia in 1969, followed by his PhD (Physiology-Pharmacology, 1974) and MD (1975) degrees from Duke University Medical School. As a PhD-MD student, Eisenbarth worked under the mentorship of Dr. Harold Lebovitz. According to Dr. Lebovitz, once Eisenbarth joined his laboratory, everyone else started working for him! Eisenbarth did not become a leader over time, he always was one.

Dr. Eisenbarth married his wife Frieda, and they had two children, Stephanie and Stephen, who are both successful in their careers. Nothing gave him more pride than his daughter becoming an immunologist and a productive researcher at Yale University. He was a loving husband, caring father, and proud grandfather. His treasures were family, friends, and his work. Always kind and polite, he was loved and respected by all who knew him and by the many he touched.

Gifted with …
Modifying Akt Signaling in B-Cell Chronic Lymphocytic Leukemia Cells
Authors: Sebastian W. Hofbauer, Josefina D. Piñón, Gabriele Brachtl, Lucia Haginger, Wei Wang, Karin Jöhrer, Ingeborg Tinhofer, Tanja Nicole Hartmann, Richard Greil
Journal: Cancer Research (2010)

Emerging evidence suggests that the survival of B-cell chronic lymphocytic leukemia (CLL) cells is dependent on microenvironmental influences such as antigenic stimulation and support by stromal cells. Akt, also known as protein kinase B, is a central component in prosurvival signaling downstream of these events. We investigated the role of Akt and its modulation by the protooncogene T-cell leukemia 1a (Tcl1a) in the survival pathways of primary CLL samples and CLL-derived prolymphocytic cell lines MEC-1 and MEC-2. Akt activation was increased by the protective presence of human bone marrow stromal cells and B-cell receptor mimicking signals but antagonized by direct Akt blockade with the novel specific inhibitor AiX, with preferential apoptosis induction in CLL cells with an unmutated immunoglobulin status, which predicts poor clinical outcome. In addition, we found a direct interaction of Akt with Tcl1a in an endogenous coimmunoprecipitation assay. Confirming the critical role of Tcl1a in modulating Akt signaling, Akt activation was enhanced by overexpressing Tcl1a in CLL. In contrast, decreasing Tcl1a levels by small interfering RNA reduced Akt activation in the fludarabine-insensitive CLL cell line MEC-2 and sensitized the malignant cells to fludarabine treatment. In summary, our data reveal a significant role for the Akt-Tcl1a axis in CLL survival and propose a further evaluation of this interplay for targeting chemoresistance phenomena.