tbuckley/cabot-search huggingface dataset:
Gut-Derived Incretin Hormones and New Therapeutic Approaches
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2004)

This is the first of a series of articles on presentations at the American Diabetes Association Annual Meeting, Orlando, Florida, 4–8 June 2004, addressing an important theme of the meeting: new therapeutic approaches based on gut-derived incretin hormones.

### Physiology of glucagon-like peptide 1 action

Alan Cherrington (Nashville, TN) described a series of studies of peripheral and hepatic arterial and portal vein flow measurement and sampling that allowed for the assessment of hepatic glucose balance and effects of glucagon-like peptide (GLP)-1. In a study comparing peripheral with portal venous glucose delivery during hyperglycemia (glucose increased from 75 to 150 mg/dl), with somatostatin to suppress endogenous insulin and glucagon and administration of glucagon to replace basal levels and insulin to levels approximately four times greater than basal, there was a similar increase in the hepatic glucose load, from ∼25 to 50 mg · kg−1 · min−1, but portal glucose delivery doubled hepatic glucose uptake. Net hepatic glucose uptake remained considerably greater with intraportal glucose delivery when the hepatic glucose load was varied from 50 to 75 to 100 mg · kg−1 · min−1. Thus, Cherrington suggested, hepatic glucose entry depends on insulin and glucose levels and a “portal signal.” Portal glucose delivery, then, can be said to “activate the liver,” which may be in part the mechanism of increased hepatic glucose uptake following oral glucose delivery. When measuring hepatic sinusoidal insulin, as levels increase, the net hepatic glucose uptake increases but there is further uptake with activation of the portal glucose signal. In further studies varying peripheral and portal vein glucose delivery and maintaining hyperinsulinemia, a fivefold increase in hepatic glucose uptake was demonstrated, as portal glucose delivery ranged from nil to 100%. Conversely, when glucose was infused peripherally versus in the portal vein at 2.5 mg · kg−1 · min …
Multidrug-resistant tuberculosis in UK children: presentation, management and outcome: Table 1–
Authors: Bhanu Williams, Shiva Ramroop, Pooja Shah, Laura Anderson, Sreena Das, Anna Riddell, Sue Liebeschuetz, Robin Basu Roy, Maria O'Callaghan, Katherine Sloper, Jolanta Bernatoniene, Delane Shingadia, Beate Kampmann
Journal: European Respiratory Journal (2013)

To the Editor: 

Multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin, is an increasing problem globally [1]. Children are not usually included in global surveys of MDR-TB incidence and prevalence [2] due to the diagnostic challenges of paucibacillary TB [3]. Data on the burden of MDR-TB in children are, therefore, lacking globally [1, 4, 5] and no published data from the UK exist. The current World Health Organization (WHO) [6] and National Institute for Clinical Excellence (NICE) [7] TB guidelines for the management of MDR-TB do not explicitly address paediatric disease. As a consequence, the complex management of this condition is left to individual clinicians' judgment. In general, childhood TB is paucibacillary, most cases are treated on clinical grounds without drug susceptibility testing [2], and correct and timely diagnosis of childhood MDR-TB is therefore challenging. There are limited data on the pharmacokinetics, dosing and safety of the many second-line drugs used to treat MDR-TB in children [5]. Our group is the first to review the management of a paediatric cohort with MDR-TB in the UK, and represents the largest available dataset from children with culture-confirmed MDR-TB from western …
New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach
Authors: H. Duffau, L. Taillandier
Journal: Neuro-Oncology (2014)

Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a "wait and see" policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity. However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation. Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring. This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL. New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology.
In Memoriam: Ernst Knobil (1926–2000)
Authors: Jimmy D. Neill
Journal: Endocrine Reviews (2001)

in his 73rd year of life, thus ending a remarkable career of outstanding scientific accomplishments, of leadership positions in physiology and endocrinology, and of mentorship to numerous students and fellows.He was noted for his clarity of thought, his endless pursuit of excellence, and his abiding interest in integrative biology.Dr. Knobil was a visionary leader and a pioneer in many areas of endocrinology, including growth and reproduction.Dr. Knobil's now classic contributions include the species-specific effects of GH, a model for positive and negative estrogen feedback control of the menstrual cycle, and elucidation of the hypothalamic GnRH pulse generator.His discovery that pulsatile GnRH stimulates LH, whereas continuous GnRH desensitizes pituitary LH secretion, has forever altered the field of reproductive endocrinology.This remarkable experimental observation unmasked a pivotal role for pulsatile secretion as a mechanism of hormonal control.The elder son of an Austrian father (Jakob Knobil) and a German mother (Regina Seidmann), Ernst was born in Berlin, Germany on September 20, 1926.When Ernst was about 6 yr old, the Knobil family moved to Paris due to the deteriorating political conditions in Germany.Then, in 1940, when the Germans invaded Paris and Ernst was 13, the family emigrated to New York City.Ernst entered the New York State College of Agriculture at Cornell in 1942, at the age of 15.He chose Animal Science as his major due to interests developed from time spent on farms in France during the summers, and from attending the Kinderhook Farm Camp, after moving to New York.Upon graduating from Cornell in 1948 (including a 2-yr interruption for service in the U.S. Army), he entered graduate school in zoology
Development of a provisional core set of response measures for clinical trials of systemic sclerosis
Authors: D Khanna, D J Lovell, E Giannini, P J Clements, P A Merkel, J R Seibold, M Matucci-Cerinic, C P Denton, M D Mayes, V D Steen, J Varga, D E Furst
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To develop a provisional core set of response measures for clinical trials of systemic sclerosis (SSc). <h3>Methods:</h3> The Scleroderma Clinical Trials Consortium (SCTC) conducted a structured, 3-round Delphi exercise to reach consensus on a core set of measures for clinical trials of SSc. Round 1 asked the SCTC investigators to list items in 11 pre-defined domains (skin, musculoskeletal, cardiac, pulmonary, cardio-pulmonary, gastrointestinal, renal, Raynaud phenomenon and digital ulcers, health-related quality of life and function, global health, and biomarkers) for SSc clinical trials. Round 2 asked respondents to rate the importance of the chosen items and was followed by a meeting, during which the Steering Committee discussed the feasibility, reliability, redundancy and validity of the items. Round 3 sought to obtain broader consensus on the core set measures. Members also voted on items that had data on feasibility but lacked data on reliability and validity, but may still be useful research outcome measures for future trials. <h3>Results:</h3> A total of 50 SCTC investigators participated in round 1, providing 212 unique items for the 11 domains. In all, 46 (92%) participants responded in round 2 and rated 177 items. The ratings of 177 items were reviewed by the Steering Committee and 31 items from the 11 domains were judged to be appropriate for inclusion in a 1-year multi-centre clinical trial. In total, 40 SCTC investigators completed round 3 and ranked 30 of 31 items as acceptable for inclusion in the core set. The Steering Committee also proposed 14 items for a research agenda. <h3>Conclusion:</h3> Using a Delphi exercise, we have developed a provisional core set of measures for assessment of disease activity and severity in clinical trials of SSc.
Abnormal Conduction and Morphology in the Atrioventricular Node of Mice With Atrioventricular Canal–Targeted Deletion of Alk3/Bmpr1a Receptor
Authors: Dina Myers Stroud, Vinciane Gaussin, John B.E. Burch, Cindy Yu, Yuji Mishina, Michael D. Schneider, Glenn I. Fishman, Gregory E. Morley
Journal: Circulation (2007)

Background— The atrioventricular (AV) node is essential for the sequential excitation and optimized contraction of the adult multichambered heart; however, relatively little is known about its formation from the embryonic AV canal. A recent study demonstrated that signaling by Alk3, the type 1a receptor for bone morphogenetic proteins, in the myocardium of the AV canal was required for the development of both the AV valves and annulus fibrosus. To test the hypothesis that bone morphogenetic protein signaling also plays a role in AV node formation, we investigated conduction system function and AV node morphology in adult mice with conditional deletion of Alk3 in the AV canal. Methods and Results— High-resolution optical mapping with correlative histological analysis of 28 mutant hearts revealed 4 basic phenotypic classes based on electrical activation patterns and volume-conducted ECGs. The frequency of AV node conduction and morphological abnormalities increased from no detectable anomalies (class I) to severe defects (class IV), which included the presence of bypass tracts, abnormal ventricular activation patterns, fibrosis of the AV node, and twin AV nodes. Conclusion— The present findings demonstrate that bone morphogenetic protein signaling is required in the myocardium of the AV canal for proper AV junction development, including the AV node.
Farmer's lung in Devon.
Authors: J T Smyth, G E Adkins, L Margaret, B Moore, E McWhite
Journal: Thorax (1975)

Farmer9s lung is a cause of disability to agricultural workers in Devon and there is no evidence that the incidence is falling. A survey of known cases was made to assess the degree of disability in relation to the clinical history, the presence of farmer9s lung precipitins, tests of lung function, and radiographic changes. Information was obtained about 200 patients diagnosed between 1939 and 1971. A survey of 148 of these patients showed that the disease was most commonly diagnosed in men aged 40 to 50 years and the most important symptom at diagnosis was dyspnoea related to occupational exposure to hay or grain. The onset was often insidious and only 67 patients (45%) were diagnosed during the first year of the disorder. Disability was severe in about one-third of the cases. The degree of disability did not seem to be related to the serological changes recorded either at diagnosis or at the time of our survey. Disability was commonly associated with restriction and reduced gas transfer factor and with airways obstruction in more severe cases. Many individuals reporting significant disability had only slightly abnormal ventilatory function tests at rest. Radiographic changes were found at survey in about one-third of the subjects reporting disability. Many farmers had not used an efficient mask. Treatment is unsatisfactory but steroid therapy is effective in acute episodes.
GFRα1 Is an Essential Receptor Component for GDNF in the Developing Nervous System and Kidney
Authors: Grace Cacalano, Isabel Fariñas, Li-Chong Wang, Kelly Hagler, Alison Forgie, Mark Moore, Mark Armanini, Heidi Phillips, Anne M Ryan, Louis F Reichardt, Mary Hynes, Alun Davies, Arnon Rosenthal
Journal: Neuron (1998)
Dietary Intake of Eicosapentaenoic and Docosahexaenoic Acid and Diabetic Nephropathy: Cohort Analysis of the Diabetes Control and Complications Trial
Authors: Cheetin C. Lee, Stephen J. Sharp, Deborah J. Wexler, Amanda I. Adler
Journal: Diabetes Care (2010)

OBJECTIVE To investigate the association between dietary n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) and the degree and development of albuminuria in type 1 diabetes. RESEARCH DESIGN AND METHODS We analyzed longitudinal data from 1,436 participants in the Diabetes Control and Complications Trial. We defined the average intake of eicosapentaenoic and docosahexaenoic acid from diet histories. Urinary albumin excretion rates (UAERs) were measured over 24 h; incident albuminuria was considered the first occurrence of an UAER &amp;gt;40 mg/24 h sustained for ≥1 year in normoalbuminuric individuals. RESULTS In a mean follow-up of 6.5 years, we observed a lower mean UAER (difference 22.7 mg/24 h [95% CI 1.6–43.8)]) in the top versus the bottom third of dietary n-3 LC-PUFAs, but we found no association with incident albuminuria. CONCLUSIONS Dietary n-3 LC-PUFAs appear inversely associated with the degree but not with the incidence of albuminuria in type 1 diabetes. These findings require further investigation in prospective studies.
Monoclonal Antibody CC188 Binds a Carbohydrate Epitope Expressed on the Surface of Both Colorectal Cancer Stem Cells and their Differentiated Progeny
Authors: Mai Xu, Yuan Yuan, Yang Xia, Samuel Achilefu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Recently, cancer stem cells (CSC), undifferentiated cancer progenitor cells, have been successfully isolated from colorectal tumors. Targeting both CSCs and differentiated, rapidly proliferating tumor cells with therapeutic drugs provides a focused strategy to treat cancer. In this study, we isolated the monoclonal antibody (mAb) CC188 and characterized the epitope recognized by mAb CC188, which is useful for developing biological reagents that target CSCs. Experimental Design: We used a hybridoma technique to generate mAbs and an immunomagnetic method to isolate colon CSCs. We characterized mAb CC188 binding epitope and examined the epitope distribution in normal and tumor tissues, particularly in CSCs using tissue arrays and immunofluorescence staining method. We also evaluated the effect of mAb CC188 on invasiveness of NSY tumor cells. Results: mAb CC188 was generated and 98.9% (187 of 189 cases) of colon cancer were positively stained by mAb CC188. “+”, “++,” and “+++” staining were 25.9%, 28.6%, and 43.4%, respectively. The mAb CC188 binding epitope was identified as a carbohydrate, which was expressed on the surface of colon CSCs (CD133+), differentiated colon cancer cells (CD133−), and cells from various types of epithelial tumors. In contrast, the expression of the carbohydrate epitope was low in normal prostate muscle and pancreatic acinar cells, as well as in some normal epithelial cells of the breast duct, cervix, and skin. A functional study indicated that mAb CC188 suppressed the invasiveness of NSY tumor cells. Conclusion: mAb CC188 selectively targets a carbohydrate epitope expressed on cancer cells, providing a viable method for specific tumor imaging and targeted therapy.
Can Ischemia Modified Albumin and Brain Natriuretic Peptide Levels Predict The Extension of Coronary Artery Disease in Low-Intermediate Risk Unstable Angina Pectoris?
Authors: Abdullah Orhan Demirtas, Turgut Karabağ, Muhammet Rasit Sayin, Ibrahim Akpinar, Nesimi Yavuz, Mustafa Aydin
Journal: Journal of the American College of Cardiology (2013)
Resistance to activated protein C: a common anticoagulant deficiency in patients with venous leg ulceration
Authors: S. MUNKVAD, M. JØRGENSEN
Journal: British Journal of Dermatology (1996)

Patients with leg ulcers caused by venous insufficiency often show evidence of previous deep venous thrombosis. Resistance to activated protein C (APC resistance) is a newly identified, autosomal dominant inherited defect in the anticoagulant system which significantly predisposes affected individuals to develop venous thrombosis. To elucidate the significance of APC resistance in venous leg ulcer patients, APC resistance was determined in plasma samples obtained from 46 unselected, consecutive patients with venous leg ulcers, admitted to hospital during a 6-month period. Twelve of the 46 patients (26%: 95% confidence limits, 14-41%) had APC resistance. APC resistance is thus a common anticoagulant deficiency among patients with venous leg ulceration and should be considered a risk factor for the development of venous leg ulcer disease.
Impairment of Executive Function But Not Memory in First-Degree Relatives of Patients With Bipolar I Disorder and in Euthymic Patients With Unipolar Depression
Authors: Luke Clark, Antonina Sarna, Guy M Goodwin
Journal: American Journal of Psychiatry (2005)

The authors' goal was to characterize cognitive flexibility and verbal learning in relatives of patients with bipolar disorder and in euthymic patients with recurrent major depression.The intradimensional/extradimensional shift task and California Verbal Learning Test were administered to 27 first-degree relatives of probands with bipolar I disorder, 15 euthymic outpatients with recurrent unipolar depression, and 47 healthy comparison subjects.The relatives of patients with bipolar I disorder and the euthymic patients with unipolar depression were more likely to fail the intradimensional/extradimensional shift task than the healthy comparison subjects. The impairments at the extradimensional shift stage were pronounced. Verbal learning, delayed recall, and recognition were unimpaired in all groups.Attentional set shifting may represent an endophenotype in mood disorder, related to underlying vulnerability rather than the actual disease phenotype.
Minimal Engagement of CD103 on Cytotoxic T Lymphocytes with an E-Cadherin-Fc Molecule Triggers Lytic Granule Polarization via a Phospholipase Cγ–Dependent Pathway
Authors: Audrey Le Floc'h, Abdelali Jalil, Katarzyna Franciszkiewicz, Pierre Validire, Isabelle Vergnon, Fathia Mami-Chouaib
Journal: Cancer Research (2011)

Abstract Interaction of the integrin αE(CD103)β7 expressed on tumor-infiltrating lymphocytes (TIL) with E-cadherin on epithelial tumor cells is required to trigger polarized exocytosis of cytotoxic granules in TIL that elicit tumor cell lysis. In this study, we investigated the functional and signaling properties of CD103 and its individual contribution to T-cell–mediated cancer-cell killing. Our results indicated that the binding of CD103 on tumor-specific CTL to immobilized recombinant E-cadherin-Fc is sufficient to induce the polarization of cytolytic granules, whereas the degranulation of cytolytic granules also requires the coengagement of the T-cell receptor. Moreover, minimal CD103 triggering promotes the phosphorylation of the ERK1/2 kinases and phospholipase Cγ1 (PLCγ1). Inhibiting PLCγ blocks granule relocalization, decreasing T-cell receptor–mediated cytotoxicity. Thus, our results emphasize a unique costimulatory role of CD103 in tumor-specific CTL activation by providing signals that promote T-cell effector functions needed to specifically target and lyse cancer cells. Cancer Res; 71(2); 328–38. ©2011 AACR.
Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study
Authors: G H Song
Journal: Gut (2005)

Melatonin, a sleep promoting agent, is involved in the regulation of gastrointestinal motility and sensation. We aimed to determine if melatonin was effective in improving bowel symptoms and sleep disturbances in irritable bowel syndrome (IBS) patients with sleep disturbance.
Chemotherapy, Trastuzumab, and Pathological Complete Response: When Shall We Three Meet Again?
Authors: David A. Cameron
Journal: Journal of Clinical Oncology (2011)

Honest, sincere, and clear writing that appeals to cardinal virtues like truth, beauty, and goodness is strongly preferred. That may seem like a tall order, but it need not be. Although the bar to publication in the AOO section is high—our acceptance rate has been less than 25% of submitted manuscripts in recent years—we embrace brand new writers and new voices of all types, including yours. The only required qualification is that an author be able to express clearly something that is important and that hasn’t been said in quite the same way before. Because of the intimate nature of many reflective essays and personal narratives, some potential AOO contributors may worry that writing a personal commentary that will be seen by thousands of readers will leave them feeling exposed or vulnerable. It is true that writers of AOO articles cannot hide behind the anonymity of data tables and Kaplan-Meier curves or trust in the formulaic, stereotyped language of the Methods section of clinical trial reports. Still, we invite you to try to overcome such inhibitions and apprehension. Your contributions may enrich our professional culture or form the basis for productive discussions. The editors of AOO encourage you to share a case or an experience with us that you found moving, interesting, or difficult, or to tell us about an aspect of medical practice that you feel passionately about that has not been featured previously in AOO. Write about what you know and what you wish other people knew, too. If you have a good story to tell, but you do not trust your own writing skills, consider working with a colleague. Every group and institution has talented communicators;perhapsacolleague isa formerEnglishmajor, forwhom turningafirst-rate ideaorapromisingroughdraft intoasparklingessay is as straightforward as calculating body surface area is to you. The diagnosis and treatment of cancer are changing rapidly and unpredictably. The role of the physician is changing, too, in response to popular expectations, shifting regulations, and ongoing evolution in the structure of health care teams. But the human experience of serious illness, as well as the importance of the physician’s presence at the bedside, remain unaltered at core. Meaningful and concise articles about those bedside experiences will engage and inform readers and shape our professional culture. We look forward to hearing from you.
Flow cytometric detection of circulating myeloma cells before transplantation in patients with multiple myeloma: a simple risk stratification system
Authors: David Dingli, Grzegorz S. Nowakowski, Angela Dispenzieri, Martha Q. Lacy, Suzanne R. Hayman, S. Vincent Rajkumar, Philip R. Greipp, Mark R. Litzow, Dennis A. Gastineau, Thomas E. Witzig, Morie A. Gertz
Journal: Blood (2005)
The β-Glucan Receptor Dectin-1 Activates the Integrin Mac-1 in Neutrophils via Vav Protein Signaling to Promote Candida albicans Clearance
Authors: Xun Li, Ahmad Utomo, Xavier Cullere, Myunghwan Mark Choi, Danny A. Milner, Deepak Venkatesh, Seok-Hyun Yun, Tanya N. Mayadas
Journal: Cell Host & Microbe (2011)