tbuckley/cabot-search huggingface dataset:
Effect of Rimonabant on Glycemic Control in Insulin-Treated Type 2 Diabetes: The ARPEGGIO Trial
Authors: Priscilla A. Hollander, Aslam Amod, León E. Litwak, Umesh Chaudhari
Journal: Diabetes Care (2009)

OBJECTIVE To examine the efficacy and safety of rimonabant, a selective cannabinoid receptor type-1 antagonist, in patients with type 2 diabetes receiving insulin monotherapy. RESEARCH DESIGN AND METHODS Patients (n = 368; A1C ≥7%) were randomized to 20 mg/day rimonabant or placebo in this 48-week, double-blind, placebo-controlled multicenter trial. Change in baseline A1C to week 48 (primary outcome) and changes in body weight, waist circumference, and lipid levels (secondary outcomes) were assessed. RESULTS Rimonabant significantly reduced baseline A1C versus placebo (−0.89 vs. −0.24%; P &amp;lt; 0.0001), and significantly greater improvements were observed in cardiometabolic risk factors. More rimonabant patients achieved &amp;gt;10% reduction in mean total daily insulin dose versus placebo (P = 0.0012), and fewer required rescue medication (P &amp;lt; 0.0001). Hypoglycemia, nausea, dizziness, anxiety, and depression were more frequent with rimonabant. CONCLUSIONS Rimonabant improved glycemic control and cardiometabolic risk factors in patients with type 2 diabetes receiving insulin.
Mirror neurons: Tests and testability
Authors: Caroline Catmur, Clare Press, Richard Cook, Geoffrey Bird, Cecilia Heyes
Journal: Behavioral and Brain Sciences (2014)

Abstract Commentators have tended to focus on the conceptual framework of our article, the contrast between genetic and associative accounts of mirror neurons, and to challenge it with additional possibilities rather than empirical data. This makes the empirically focused comments especially valuable. The mirror neuron debate is replete with ideas; what it needs now are system-level theories and careful experiments – tests and testability.
Achilles tendon rupture and sciatica: a possible correlation.
Authors: N Maffulli, A S Irwin, M G Kenward, F Smith, R W Porter
Journal: British Journal of Sports Medicine (1998)

The association between Achilles tendon rupture and sciatica was investigated by questionnaire in 138 patients who underwent repair of an Achilles tendon rupture, and in a group of individuals nominated by the patients, matched for age, sex, and occupation. A total of 102 patients (74%) and 128 peer nominated controls (71%) replied to the questionnaire. Of the 102 respondent patients, 18 had an officebased job, 47 were involved in skilled nonmanual work, and 16 were retired. Back pain had been experienced by 63 of the patients who replied to the questionnaire, and by 91 (75%) of the individuals in the control group (difference not significant). In about 30% of both groups, the pain confined them to bed for at least two days, and resulted in absence from work. Thirteen of the patients and 16 of the controls had undergone thoracic, lumbar, or sacral radiography. One individual in each group had received surgery for back pain. However, 35 of 102 patients had experienced sciatic pain before Achilles tendon rupture. Pain of a similar nature had been experienced by only 15 individuals in the control group (12%) (p &lt; 0.001). Using this study design, we found a highly significant association between Achilles tendon rupture and sciatica. We propose that this association could be due to impaired afferent signals from the lower leg, or to similar collagen or vascular anomalies of the vertebral disc and the Achilles tendon.
Localized Amyloidosis at the Site of Repeated Insulin Injection in a Patient With Type 2 Diabetes
Authors: Shintaro Okamura, Yasuaki Hayashino, Satoshi Kore-Eda, Satoru Tsujii
Journal: Diabetes Care (2013)

We present the case of a 69-year-old woman with type 2 diabetes mellitus who developed severe insulin resistance associated with insulin injections into a subcutaneous mass formed by repeated injections into the same site over many years. The patient (height, 150 cm; weight, 79 kg; BMI, 35.1 kg/m2) was admitted to Tenri Hospital with severe insulin resistance. She was undergoing insulin therapy since 56 years of age. Her glycemic control was fair until 63 years of age, after which it worsened and necessitated an increase in her insulin dose. This led to a 15-kg increase in body weight. On admission, her insulin regimen comprised a single injection of 33 units of neutral protamine Hagedorn insulin at bedtime and three daily injections of 33 units of premixed human insulin (70/30) before each meal. …
Frontiers in Nephrology
Authors: Michael S Goligorsky
Journal: Journal of the American Society of Nephrology (2007)

“Intestinal appendix! Kidney!” he said to himself, “It's not a question of the appendix, not a question of the kidney, but a question of life and…death.” —Leo Tolstoy, The Death of Ivan Ilyitch Angina pectoris was first described by William Heberden in 1772, but the pathology of the
Impact of gene dosage, loss of wild-type allele, and FLT3 ligand on Flt3-ITD–induced myeloproliferation
Authors: Shabnam Kharazi, Adam J. Mead, Anna Mansour, Anne Hultquist, Charlotta Böiers, Sidinh Luc, Natalija Buza-Vidas, Zhi Ma, Helen Ferry, Debbie Atkinson, Kristian Reckzeh, Kristina Masson, Jörg Cammenga, Lars Rönnstrand, Fumio Arai, Toshio Suda, Claus Nerlov, Ewa Sitnicka, Sten Eirik W. Jacobsen
Journal: Blood (2011)
Ki-67 Staining Index Predicts Distant Metastasis and Survival in Locally Advanced Prostate Cancer Treated With Radiotherapy
Authors: Rile Li, Kateri Heydon, M. Elizabeth Hammond, David J. Grignon, Mack Roach, Harvey B. Wolkov, Howard M. Sandler, William U. Shipley, Alan Pollack
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Proliferative activity defined by Ki-67 staining index (SI) has been correlated with progression and prognosis in a number of malignant tumors including prostate cancer. However, few studies have examined Ki-67 SI in pretreatment diagnostic material from patients treated with definitive radiotherapy. In a prior study, we found that a Ki-67 SI of &amp;gt;3.5% was associated with poorer patient outcome. The goals of this analysis were to validate the prognostic value of Ki-67 SI and this cut point. Experimental Design: Of 456 assessable patients in Radiation Therapy Oncology Group Protocol 86-10, diagnostic material from 108 patients was available for Ki-67 analysis using MIB-1 antibody. Sixty patients were treated with external beam radiotherapy (EBRT) alone, and 48 patients were treated with short-term androgen deprivation + EBRT. Median follow-up was 9 years for those living. The relationship of Ki-67 with distant metastasis (DM), disease-specific survival (DSS), and overall survival (OS) was examined. Results: The median Ki-67 SI was 7.1% (range, 0.2–45.5%). The 7.1% cut point was associated with DM and DSS; however, the 3.5% cut point was as strong a determinant and was the focus of this analysis. In Cox proportional hazards regression, Ki-67 SI was independently associated with DM and DSS. When the Ki-67 SI was ≤3.5% and &amp;gt;3.5%, the 5-year risk of DM was 13.5% and 50.8% (P = 0.0005), respectively, and the 5-year risk of DSS was 97.3% and 67.7% (P = 0.0039), respectively. No association of Ki-67 SI with OS was observed. Conclusions: Higher Ki-67 SI was significantly associated with a greater risk of DM and DSS in locally advanced prostate cancer after definitive EBRT or AD + EBRT.
TUBERCULOSIS OF THE SKIN IN HONG KOKG (A REVIEW OF 160 CASES)
Authors: K. O. WONG, K. P. LEE, S. F. CHIU
Journal: British Journal of Dermatology (1968)

SUMMARY.— 160 cases of tuberculosis of the skin seen in the Government Dermatological Clinics in Hong Kong are reviewed. Tuberculosis verrucosa was the commonest form and accounted for 46% of cases. The onset was below the age of 20 in 77% of these patients. The distribution of the lesions differed from that reported by most recent authors. The knees, thighs and buttocks were commonly affected. In 3 of 9 cases of papulonecrotic tuberculid in men the penis was involved. The degree of sensitivity to tuberculin appeared to be similar in all forms of cutaneous tuberculosis. Pulmonary infection was associated in about 10% of cases of cutaneous tuberculosis. The factors possibly responsible for the differences between the present and other series of cases are briefly discussed.
Ion Channels in Innate and Adaptive Immunity
Authors: Stefan Feske, Heike Wulff, Edward Y. Skolnik
Journal: Annual Review of Immunology (2015)

Ion channels and transporters mediate the transport of charged ions across hydrophobic lipid membranes. In immune cells, divalent cations such as calcium, magnesium, and zinc have important roles as second messengers to regulate intracellular signaling pathways. By contrast, monovalent cations such as sodium and potassium mainly regulate the membrane potential, which indirectly controls the influx of calcium and immune cell signaling. Studies investigating human patients with mutations in ion channels and transporters, analysis of gene-targeted mice, or pharmacological experiments with ion channel inhibitors have revealed important roles of ionic signals in lymphocyte development and in innate and adaptive immune responses. We here review the mechanisms underlying the function of ion channels and transporters in lymphocytes and innate immune cells and discuss their roles in lymphocyte development, adaptive and innate immune responses, and autoimmunity, as well as recent efforts to develop pharmacological inhibitors of ion channels for immunomodulatory therapy.
Sickle cell trait: what's a sports medicine clinician to think?
Authors: Francis G O'Connor, Patricia Deuster, Alexis Thompson
Journal: British Journal of Sports Medicine (2012)

In April of 2010, the National Collegiate Athletic Association (NCAA), supported by other professional organisations (College of American Pathologists 2007; National Athletic Trainers' Association 2007) approved mandatory testing for the presence of sickle cell carrier status in student athletes participating in Division I sports. This action was in part a response to the legal case against the NCAA and Rice University brought forward by the family of Dale Lloyd II. Dale Lloyd's death was attributed to exertional rhabdomyolysis associated with sickle cell trait; this association has been described in the medical literature in athletes, as well as in military populations.1 

Mandatory testing, although implemented to prevent future deaths, has generated controversy. Whereas some believe that screening or a priori knowledge of sickle cell trait (SCT) status may potentially save lives, others argue that screening may do more harm than good. In January 2012, the American Society of Haematology (ASH), which represents over 16 000 physicians and researchers, issued a statement opposing SCT testing and/or disclosure of status as a prerequisite for athletic participation.2 They stated that screening cannot be justified based on current scientific evidence. In contrast, ASH supports implementation of universal guidelines to reduce exertion-related injuries and deaths. Given the strong and contrasting opinions, physicians and other providers are left wondering how to properly advise athletes, in particular those who may not fall under recommendations of the NCAA. Their policy has been supported by several other medical organisations, including the American Society of Pediatric Hematology Oncology, American Public Health Association, Sickle Cell Disease Association of …
Regulation of interleukin 1α secretion by inflammasomes: Table 1
Authors: Amir S Yazdi, Stefan K Drexler
Journal: Annals of the Rheumatic Diseases (2012)

The crucial role of the proinflammatory cytokine interleukin 1β (IL-1β) in driving inflammatory disorders, such as Muckle–Wells syndrome and gout, has been extensively characterised. Owing to its high potency to induce inflammation the activation and secretion of IL-1β is tightly regulated. The sensing of various host 'dangers', including infections and metabolic deregulation, results in the formation of large protein complexes, termed inflammasomes. Formation of the inflammasomes leads to the cleavage and activation of caspase-1, which in turn proteolytically processes its substrates, including pro-IL-1β. Biologically active IL-1β is subsequently secreted by the cell. In contrast to IL-1β, little is known about mechanisms underlying the activation and secretion of its close homologue IL-1α. Moreover, the physiological role of IL-1α is still not well defined. Several studies hypothesise that IL-1α serves as a danger signal, which is passively released from dying cells. However, recent studies suggest a more complex function of this cytokine. Indeed, NLRP3 inflammasome agonists such as uric acid crystal or nigericin induce IL-1α cleavage and secretion, leading to the cosecretion of both IL-1β and IL-1α. Depending on the type of NLRP3 agonist, release of IL-1α is NLRP3-inflammasome/caspase-1 dependent or independent, but in both cases IL-1α processing depends on calpain protease activity. Taken together, these results suggest that the promotion and progression of inflammatory diseases is not solely due to IL-1β but also to its close relative IL-1α. This should be considered when IL-1 blockade is applied as a therapeutic strategy for diseases such as cryopyrin-associated periodic syndromes or gout.
SPECIAL FUND: TRADE UNION OR TRUST?
Authors: D. Roberts
Journal: BMJ (1914)

The endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) bind to G protein-coupled central and peripheral cannabinoid receptors CB1 and CB2, respectively. Due to the relatively high expression of the CB2 isotype on peripheral immune cells, it has been hypothesized that this receptor mediates the immunosuppressive effects of cannabinoids. Unfortunately, there was a dearth of pharmacological studies with the endocannabinoids and human CB2 (hCB2). These studies compare and contrast the potency and efficacy of anandamide, 2-AG, and the synthetic cannabinoid HU210 at hCB2. Using [<sup>35</sup>S]guanosine-5′-<i>O</i>-(3-thio)triphosphate (GTPγS) and radioligand bindings in insect Sf9-hCB2 membranes, we showed that both endocannabinoids bound hCB2 with similar affinity and that the cannabinoids acted as full agonists in stimulating [<sup>35</sup>S]GTPγS exchange, although 2-AG was 3-fold more potent than anandamide (EC<sub>50</sub> = 38.9 ± 3.1 and 121 ± 29 nM, respectively). In a mammalian expression system (Chinese hamster ovary-hCB2 cells), HU210 and 2-AG maximally inhibited forskolin-stimulated cAMP synthesis (IC<sub>50</sub> = 1.61 ± 0.42 nM and 1.30 ± 0.37 μM, respectively) although anandamide was ineffective. In Chinese hamster ovary-hCB2 membranes, HU210 and 2-AG were also full agonists in stimulating [<sup>35</sup>S]GTPγS binding (EC<sub>50</sub> = 1.96 ± 0.35 and 122 ± 17 nM, respectively), but anandamide was a weak partial agonist (EC<sub>50</sub> = 261 ± 91 nM; 34 ± 4% of maximum). Due to its low intrinsic activity, coincubation with anandamide effectively attenuated the functional activity of 2-AG at hCB2. Collectively, the data showed that both endocannabinoids bound hCB2 with similar affinity, but only 2-AG functioned as a full agonist. Moreover, the agonistic activity of 2-AG was attenuated by anandamide.
To clip or not to clip? Noseclips for spirometry
Authors: R. Chavasse, P. Johnson, J. Francis, I. Balfour-Lynn, M. Rosenthal, A. Bush
Journal: European Respiratory Journal (2003)

The use of noseclips for open-circuit spirometry is sporadic, despite guidelines encouraging their use. The authors aimed to evaluate whether noseclips significantly affected measurements of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in children attending a tertiary, paediatric respiratory centre. Children attending the asthma and cystic fibrosis (CF) clinics were asked to perform two sets of spirometry, one with and one without noseclips in random order, 20-min apart. Paired data was obtained on 62 patients (32 asthma, 30 CF) with a median age of 11.4 yrs (range 7.2-17.2 yrs). There were no systematic differences in FEV1 or FVC measured with and without noseclips, although seven children (11%) had clinically significant differences in FEV1 of >190 mL. There is no clear advantage to wearing noseclips when performing open-circuit spirometry. Individuals should be assessed to ascertain their optimal technique, which should then be used consistently in clinical practice. Noseclips should probably be retained for research protocols.
Hoxb4-YFP reporter mouse model: a novel tool for tracking HSC development and studying the role of Hoxb4 in hematopoiesis
Authors: David Hills, Ruby Gribi, Jan Ure, Natalija Buza-Vidas, Sidinh Luc, Sten Eirik W. Jacobsen, Alexander Medvinsky
Journal: Blood (2011)
Idiotype variant cell populations in patients with B cell lymphoma.
Authors: W L Carroll, J N Lowder, R Streifer, R Warnke, S Levy, R Levy
Journal: The Journal of Experimental Medicine (1986)

Using isolated idiotype (Id) protein we generated panels of antibodies in two patients with follicular lymphoma, one of whom had never received prior chemo-or radiotherapy. Flow cytometry and frozen section tissue staining of tumor with these monoclonal antibodies (mAb) revealed multiple subpopulations within each tumor. Individual mAb stained between 7% and 83% of surface Ig+ cells in the tumor samples. These subpopulations were overlapping and no single antibody recognized all the tumor cells. However, combinations of antibodies seemed to capture total tumor in both cases. In some instances, the percentage of tumor stained by a single mAb varied over time, and differed between lymph nodes sampled at the same time. Because a single species of Id protein was used to generate mAb in each case, it appears that the antibodies were directed against idiotopes variably shared by different populations within each tumor, and this was confirmed by crossblocking studies. Tumor cells from one patient were fused to a nonsecreting heteromyeloma line K6H6/B5, and most of the resulting hybrids secreted Id protein. Four mAb were used to screen the Id proteins secreted by these hybrids, and 11 different variants (16 maximal) were found. Southern blot analysis of rearranged Ig genes was done in two hybrids and biopsy material. Identically rearranged light-chain genes were seen but it appeared as though extensive somatic variation had occurred in heavy chain genes. These studies indicate that: striking Id variation can exist at diagnosis in untreated patients, the percentage of tumor represented by an individual variant may change with time and may differ between tumor sampled from different anatomical locations, and somatic variation appears to be responsible for the observed heterogeneity. Although this degree of variation makes anti-Id antibody therapy more difficult, appropriate combinations of mAb should be more efficacious than single antibodies in such cases.
Modification of the flow-generating capability of the canine heart-lung compartment by the carotid sinus baroreceptor reflex.
Authors: D P Kostiuk, K Sagawa, A A Shoukas
Journal: Circulation Research (1976)

To quantitatively understand how the carotid sinus baroreceptor reflex modifies the Starling curve (i.e., the aortic flow (AF)-mean right atrial pressure (MRAP) relationship), experiments were performed in closed-chest, naturally breathing, and anesthetized dogs before and after vagotomy. Mean aortic pressure (MAP) was fixed at approximately 100 mm Hg and the pressure in the isolated carotid sinus (ISP) was varied from 75 to 150 mm Hg in steps of 25 mm Hg. At each ISP, MRAP was slowly increased and decreased while measuring AF by a previously implanted electromagnetic flow probe. A family of AF-MRAP relation curves specified at the different ISP's were thus obtained. Third-order polynomials in MRAP and ISP adequately fit these curves. Whether the vagi were intact or cut, there was no significant difference between the AF-MRAP relation curves obtained at an ISP of 75 or 100 mm Hg. However, decreasing ISP from 125 to 100 mm Hg caused a 24% increase in AF, and increasing ISP to 150 mm Hg caused a 15% decrease in AF in the dogs with intact vagus nerves. For the vagotomized dogs, the same decrease or increase in ISP caused a 17% increase or a 21% decrease in AF, respectively. When MAP was allowed to change by the reflex, only insignificant changes in AF occurred. We conclude that the carotid sinus reflex significantly alters the flow-generating ability of the heart-lung compartment by as much as 40% but this becomes clearly observable only if the reflex change in aortic pressure is prevented.
Long-term function of parathyroid subcutaneous autoimplantation after presumed total parathyroidectomy in the treatment of secondary hyperparathyroidism. A clinical retrospective study
Authors: G. Conzo, C. Della Pietra, E. Tartaglia, C. Gambardella, C. Mauriello, A. Palazzo, L. Santini, L. Fei, G. Rossetti, G. Docimo, A. Perna
Journal: International Journal of Surgery (2014)
Decrease of delayed rectifier currents in the subacute phase of infarction
Authors: M Veldkamp
Journal: Cardiovascular Research (2000)

See article by Jiang et al. [1] (pages 34–43) in this issue. 

The paper of Jiang et al. [1] in this issue of Cardiovascular Research – ‘Delayed rectifier K currents have reduced amplitudes and altered kinetics in myocytes from infarcted canine ventricle’ – forms the coping-stone in a long series of investigations into the mechanisms underlying arrhythmias post myocardial infarction (in terms of altered ionic currents). In this paper, delayed rectifier currents were characterized in ventricular myocytes isolated from the surviving layer of epicardium overlying a 5 day-old infarct, the epicardial borderzone (EBZ).

This canine model of myocardial infarction, caused by complete occlusion of the left anterior descending coronary artery, has been thoroughly studied over the past decades. It has been demonstrated that during the healing phase post infarction (days to weeks after coronary occlusion), inducible ventricular tachycardias are a consequence of reentrant excitation localized to this EBZ (see for review [2]). Previous experimental studies on whole hearts and multicellular preparations already indicated important changes in cellular electrophysiology in the EBZ besides changes in anatomy relevant for reentry. Electrophysiological properties of the surviving epicardial fibers 5 days after coronary occlusion are characterized by a reduction in resting membrane potential, action potential amplitude and Vmax of phase 0 (upstroke velocity), partly contributing to slowed conduction. Additionally, action potentials had a brief plateau phase and thereby action potential duration was decreased [2,3]. Despite the latter, prolonged effective and relative refractory periods were observed … 

* Tel.: +31-20-566-3269; fax: +31-20-697-5458 m.w.veldkamp{at}amc.uva.nl
A haplome alignment and reference sequence of the highly polymorphic Ciona savignyi genome
Authors: Kerrin S Small, Michael Brudno, Matthew M Hill, Arend Sidow
Journal: Genome biology (2007)

The sequence of Ciona savignyi was determined using a whole-genome shotgun strategy, but a high degree of polymorphism resulted in a fractured assembly wherein allelic sequences from the same genomic region assembled separately. We designed a multistep strategy to generate a nonredundant reference sequence from the original assembly by reconstructing and aligning the two 'haplomes' (haploid genomes). In the resultant 174 megabase reference sequence, each locus is represented once, misassemblies are corrected, and contiguity and continuity are dramatically improved.
Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study
Authors: Pieter J Vlaar, Tone Svilaas, Iwan C van der Horst, Gilles FH Diercks, Marieke L Fokkema, Bart JGL de Smet, Ad FM van den Heuvel, Rutger L Anthonio, Gillian A Jessurun, Eng-Shiong Tan, Albert JH Suurmeijer, Felix Zijlstra
Journal: The Lancet (2008)