tbuckley/cabot-search huggingface dataset:
Glucose- and GTP-dependent stimulation of the carboxyl methylation of CDC42 in rodent and human pancreatic islets and pure beta cells. Evidence for an essential role of GTP-binding proteins in nutrient-induced insulin secretion.
Authors: A Kowluru, S E Seavey, G Li, R L Sorenson, A J Weinhaus, R Nesher, M E Rabaglia, J Vadakekalam, S A Metz
Journal: Journal of Clinical Investigation (1996)

Several GTP-binding proteins (G-proteins) undergo post-translational modifications (isoprenylation and carboxyl methylation) in pancreatic beta cells. Herein, two of these were identified as CDC42 and rap 1, using Western blotting and immunoprecipitation. Confocal microscopic data indicated that CDC42 is localized only in islet endocrine cells but not in acinar cells of the pancreas. CDC42 undergoes a guanine nucleotide-specific membrane association and carboxyl methylation in normal rat islets, human islets, and pure beta (HIT or INS-1) cells. GTPgammaS-dependent carboxyl methylation of a 23-kD protein was also demonstrable in secretory granule fractions from normal islets or beta cells. AFC (a specific inhibitor of prenyl-cysteine carboxyl methyl transferases) blocked the carboxyl methylation of CDC42 in five types of insulin-secreting cells, without blocking GTPgammaS-induced translocation, implying that methylation is a consequence (not a cause) of transfer to membrane sites. High glucose (but not a depolarizing concentration of K+) induced the carboxyl methylation of CDC42 in intact cells, as assessed after specific immunoprecipitation. This effect was abrogated by GTP depletion using mycophenolic acid and was restored upon GTP repletion by coprovision of guanosine. In contrast, although rap 1 was also carboxyl methylated, it was not translocated to the particulate fraction by GTPgammaS; furthermore, its methylation was also stimulated by 40 mM K+ (suggesting a role which is not specific to nutrient stimulation). AFC also impeded nutrient-induced (but not K+-induced) insulin secretion from islets and beta cells under static or perifusion conditions, whereas an inactive structural analogue of AFC failed to inhibit insulin release. These effects were reproduced not only by S-adenosylhomocysteine (another methylation inhibitor), but also by GTP depletion. Thus, the glucose- and GTP-dependent carboxyl methylation of G-proteins such as CDC42 is an obligate step in the stimulus-secretion coupling of nutrient-induced insulin secretion, but not in the exocytotic event itself. Furthermore, AFC blocked glucose-activated phosphoinositide turnover, which may provide a partial biochemical explanation for its effect on secretion, and implies that certain G-proteins must be carboxyl methylated for their interaction with signaling effector molecules, a step which can be regulated by intracellular availability of GTP.
Adventitial transduction of lentivirus-shRNA-VEGF-A in arteriovenous fistula reduces venous stenosis formation
Authors: Binxia Yang, Rajiv Janardhanan, Pawan Vohra, Eddie L. Greene, Santanu Bhattacharya, Sarah Withers, Bhaskar Roy, Evelyn C. Nieves Torres, Jaywant Mandrekar, Edward B. Leof, Debabrata Mukhopadhyay, Sanjay Misra
Journal: Kidney International (2013)

Venous neointimal hyperplasia (VNH) causes hemodialysis vascular access failure. Here we tested whether VNH formation occurs in part due to local vessel hypoxia caused by surgical trauma to the vasa vasorum of the outflow vein at the time of arteriovenous fistula placement. Selective targeting of the adventitia of the outflow vein at the time of fistula creation was performed using a lentivirus-delivered small-hairpin RNA that inhibits VEGF-A expression. This resulted in significant increase in mean lumen vessel area, decreased media/adventitia area, and decreased constrictive remodeling with a significant increase in apoptosis (increase in caspase 3 activity and TUNEL staining) accompanied with decreased cellular proliferation and hypoxia-inducible factor-1α at the outflow vein. There was significant decrease in cells staining positive for α-smooth muscle actin (a myofibroblast marker) and VEGFR-1 expression with a decrease in MMP-2 and MMP-9. These results were confirmed in animals that were treated with humanized monoclonal antibody to VEGF-A with similar results. Since hypoxia can cause fibroblast to differentiate into myofibroblasts, we silenced VEGF-A gene expression in fibroblasts and subjected them to hypoxia. This decreased myofibroblast production, cellular proliferation, cell invasion, MMP-2 activity, and increased caspase 3. Thus, VEGF-A reduction at the time of arteriovenous fistula placement results in increased positive vascular remodeling.
The Effects of Medical Management on the Progression of Diabetic Retinopathy in Persons with Type 2 Diabetes
Authors: Emily Y. Chew, Matthew D. Davis, Ronald P. Danis, James F. Lovato, Letitia H. Perdue, Craig Greven, Saul Genuth, David C. Goff, Lawrence A. Leiter, Faramarz Ismail-Beigi, Walter T. Ambrosius
Journal: Ophthalmology (2014)
The use of the dermatoscope to identify early melanoma using the three-colour test: reply from authors
Authors: R.M. Mac Kie, C.J. Fleming, P. Jarrett
Journal: British Journal of Dermatology (2002)

Journal Article The use of the dermatoscope to identify early melanoma using the three‐colour test: reply from authors Get access R.M. Mac Kie, R.M. Mac Kie Department of Public Health, University of Glasgow, Glasgow G12 R2, U.K. E‐mail: R.M.Mackie@clinmed.gla.ac.uk Search for other works by this author on: Oxford Academic Google Scholar C.J. Fleming, C.J. Fleming Department of Public Health, University of Glasgow, Glasgow G12 R2, U.K. E‐mail: R.M.Mackie@clinmed.gla.ac.uk Search for other works by this author on: Oxford Academic Google Scholar P. Jarrett P. Jarrett Department of Public Health, University of Glasgow, Glasgow G12 R2, U.K. E‐mail: R.M.Mackie@clinmed.gla.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 6, 1 December 2002, Page 1279, https://doi.org/10.1046/j.1365-2133.2002.05000_13.x Published: 01 December 2002
Assessment of current test procedures.
Authors: A K Palmer
Journal: Environmental Health Perspectives (1976)

The belief that screening tests for teratogenicity are of low predictive value has many supporters who point to the inconsistency with which malformations are induced. However, to fault the test systems when such inconsistency is predictable from both the inherently unstable nature of a malformation and from fundamental principles of teratology, is unrealistic, and, as is shown, perhaps the greater faults lie with the critics. It is suggested by examples that, if attention was concentrated not on the inconsistent malformations but on more consistent embryopathic effects which in one form or another are always associated with malformations, the predictive value of the screening tests would appear in a more favorable light. Thus, even if malformations are not demonstrated, the range of conditions (dosages) in which they might occur can be determined. Such information, used in conjunction with that obtained from other preclinical studies, can then form a reasonably sound basis for extrapolation to man.
Tertiary cancer services in Britain: benchmarking study of activity and facilities at 12 specialist centres
Authors: M A Richards, J C Parrott
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To collate information on current activity and facilities in British hospitals to assist the planning of future cancer services. <b>Design</b>: 12 hospitals delivering specialist cancer services provided information on the size of population served, activity levels related to non-surgical oncology for 1994-5, and facilities available. Inconsistencies in the recording of data were resolved through meetings of all participants. <b>Setting</b>: Five single specialty NHS trusts and seven specialist cancer facilities within multispecialty trusts, serving a combined population of 24.3 million. <b>Main outcome measures</b>: Activity levels and facilities per million population served. <b>Results</b>: The facilities available per million population served varied widely between centres. In contrast, the range in the number of new referrals per million population (seen either at the centre or in peripheral clinics) was relatively small. Considerable variations were observed in the number of attendances per patient and amount of radiotherapy and chemotherapy delivered. Overall it was estimated that 40-45% of all new cases of cancer are currently being referred to nonsurgical oncologists. For the seven hospitals which could provide data on trends in activity, the average increase in chemotherapy day case episodes between 1992-3 and 1994-5 was 83%. <b>Conclusions</b>: The results of this study provide a benchmark both for purchasers and providers of cancer care. The increase in the use of chemotherapy points to an urgent need for a unified system for monitoring both activity and outcomes of treatment.
A Comparison of Regional Blood Flow and Oxygen Utilization During Dynamic Forearm Exercise in Normal Subjects and Patients with Congestive Heart Failure
Authors: ROBERT ZELIS, JOHN LONGHURST, ROBERT J. CAPONE, DEAN T. MASON, Robert Kleckner
Journal: Circulation (1974)

Patients with severe congestive heart failure (CHF) have been found to have a diminished response to the metabolic arteriolar dilator stimulus of ischemia. In order to evaluate a more physiologic stimulus and the possible metabolic consequences of this vascular abnormality, 22 normal subjects (N) and seven patients with severe CHF performed rhythmic forearm exercise by squeezing a rubber bulb to 25, 50, or 100 mm Hg for 5 sec, four times/min, for 5 min. During the last half of the 10 sec relaxation phases, forearm blood flow (FBF) was measured plethysmographically. Not only was FBF reduced at rest in CHF (CHF:2.00 ± 0.31; N: 3.10 ± 0.27 ml/min·100 ml, P &lt; 0.02) but it was reduced at each level of exercise as well (CHF: 4.05 ± 0.71, 5.57 ± 0.71, 6.68 ± 3.09; N: 7.10 ± 0.76, 11.15 ± 1.24, 20.32 ± 1.93 ml/min·100 ml, P &lt; 0.01). Forearm oxygen extraction, calculated from brachial venous and systemic arterial blood, was consistently increased in CHF and was sufficient to maintain a normal forearm oxygen consumption at rest (CHF: 0.14 ± 0.04; N: 0.12 ± 0.01 ml O 2 /min · 100 ml, P &lt; 0.5). During exercise the calculated index of oxygen consumption was reduced at all levels of exercise (CHF: 0.30 ± 0.04, 0.48 ± 0.09, 0.54 ± 0.14; N: 0.51 ± 0.05, 0.89 ± 0.08, 1.63 ± 0.13 ml O 2 /min · 100 ml, P &lt; 0.01). These differences persisted despite alpha-adrenergic blockade with phentolamine and suppression of skin flow in N by epinephrine iontophoresis. Therefore, at comparable levels of dynamic forearm exercise patients with CHF have an inadequate arteriolar dilation and their augmented oxygen extraction is not sufficient to prevent them from shifting more completely to anaerobic metabolism.
Angiographic and hemodynamic determinants of myocardial ischemia during adenosine thallium-201 scintigraphy in coronary artery disease.
Authors: S Nishimura, K T Kimball, J J Mahmarian, M S Verani
Journal: Circulation (1993)

Myocardial ischemia attributed to coronary steal may occur in some patients receiving pharmacological coronary vasodilation. ECG ST-segment depression is a marker of myocardial ischemia in these patients, but the factors determining the presence or absence of ischemia are not well known.To examine the angiographic, hemodynamic, and scintigraphic determinants of adenosine-induced ischemic ST-segment depression in patients with coronary artery disease, we studied 65 consecutive patients (45 men and 20 women; mean age, 65 +/- 12 years) who showed reversible perfusion defects during adenosine (140 micrograms.kg-1.min-1 for 6 minutes) 201Tl single-photon emission computed tomography. Patients with prior myocardial infarction were excluded. Ischemic ST depression occurred in one third of the whole cohort (22 of 65 patients). The presence of coronary collateral vessels (p = 0.001), systolic blood pressure at baseline (p = 0.006), and adenosine-induced anginal chest pain (p = 0.011) were the only significant independent predictors of ischemic ST-segment depression by stepwise logistic regression analysis. Rate-pressure product at baseline, systolic blood pressure, heart rate, rate-pressure product, increase in heart rate, and rate-pressure product during adenosine infusion and maximal percent stenosis were variables also significantly related to ischemic ST depression by univariate analysis but were not predictive after the three primary variables were included in the regression model. Perfusion defect size, number of diseased vessels, and age did not correlate with ST-segment depression.The presence of collaterals, which may predispose to coronary collateral steal, is the most significant correlate of ischemic ST-segment depression during adenosine infusion. Systolic blood pressure at baseline, which may affect the myocardial oxygen supply/demand ratio and anginal chest pain induced by adenosine, are additional variables related to ischemic ST-segment depression during adenosine infusion.
Reassessment of the Role of Inferior-Vena-Cava Ligation in Venous Thromboembolism
Authors: Donald C. Nabseth, John M. Moran
Journal: New England Journal of Medicine (1965)

ALTHOUGH ligation of the inferior vena cava for prevention of pulmonary emboli is being performed increasingly often a difference of opinion still exists regarding the choice between inferior-vena-cava ligation, femoral-vein ligation and anticoagulation. In addition, the advisability of inferior-vena-cava ligation in critically ill patients and specifically in symptomatic cardiac patients is open to question.1 , 2 Lastly, the degree of late sequelae that may be expected in the lower extremities after ligation of the inferior vena cava is not completely clear from the existing published reports.1 2 3 4 5 6 7 8 9 If one assumes that every pulmonary embolism is potentially fatal the choice of therapy for . . .
UNNECESSARY RESTRICTIONS IN SURGERY.Read in the Section of Surgery and Anatomy at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: JOHN B. ROBERTS
Journal: JAMA (1893)

While I fully appreciate the need for caution and care in all departments of medicine, I have of late years come to believe that patients are often subjected to restrictions which add to their discomfort, without bringing any commensurate advantage in shortening the time of recovery or guaranteeing the permanency of cure. The inaccuracy of our former knowledge of the causes of surgical complications and a college teaching, which gives little opportunity for the exercise of individual judgment, have tended to make the timid or inexperienced practitioner follow with blind zeal the dogmatic assertions of writers and teachers of recognized authority. It is true that it is better to err on the side of caution than to expose a patient to unwarranted risk in a desire to give him greater liberty. On the other hand, the establishment of a nervous dread in the mind of an invalid is one of
OP0022-HPR Developing an Intervention on the Internet for Health Enhancing Physical Activity Behavior in Individuals with Rheumatoid Arthritis: Patients’ Experiences and Innovations
Authors: Å. Revenäs, C. H. Opava, P. Åsenlöf
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Despite the growing evidence for the benefits of physical activity in the population of rheumatoid arthritis (RA), the majority does not meet the recommendations of health enhancing physical activity (HEPA). One solution tried to facilitate adoption and maintenance of HEPA behavior is to derive intervention strategies from health behavior change theories and to make them available over the internet. Using principles from design science i.e. take advantages of users' experiences during the development of the internet-based HEPA intervention (IHI), may improve its quality and feasibility (1). <h3>Objectives</h3> The aim was to explore experiences and innovations on crucial aspects for adoption and maintenance of HEPA. Another aim was to identify participants' innovations regarding the most important content in a future IHI. <h3>Methods</h3> This study reports from the first step of participant involvement. Six focus groups were performed with a strategic sample of 26 individuals with RA. A semi-structured interview guide was used addressing the two overall questions. The data was analyzed using an inductive qualitative content analysis. <h3>Results</h3> Seven categories were described as crucial for adoption and maintenance of HEPA: personal incentives, personal mastering, information adapted to the RA condition, peer support, professional coaching, physical environment and resources and societal subventions. Six categories were identified including important functionalities on a future IHI: up-to-date and evidence-based information and instructions, self-regulation tools, chat-groups and fora for social interaction, customized options, the interface and access to the IHI. <h3>Conclusions</h3> This is, to the best of our knowledge, the first study involving individuals with RA in the development of an internet-based HEPA intervention. By applying a participatory design, we acknowledge patients' experiences and innovations as valid knowledge. As a consequence, the future IHI may fit users' needs and improve the possibility for a successful implementation. <h3>References</h3> Bate P, Robert G. Experience-based design: from redesigning the system around the patient to co-designing services with the patient. Qual Saf Health Care 2006;15:307-10. <h3>Disclosure of Interest</h3> None Declared
Electrohydrothermoprobe--a simple alternative to laser therapy in the management of acute gastrointestinal haemorrhage.
Authors: C M Bate, L A Aziz
Journal: Gut (1985)

One hundred and twenty six consecutive patients presenting with upper alimentary bleeding were endoscoped. Seventeen gastric and 11 duodenal lesions with visible blood vessels were identified and cauterised with the electrohydrothermoprobe. One gastric and four duodenal vessels rebled, necessitating surgery. For the gastric vessels this represents about one tenth of the expected rebleeding rate, and is a significant reduction. The technique appears to have no effect on the rebleeding rate in duodenal vessels.
STUDIES ON TISSUE UPTAKE OF INSULIN IN MAN USING A DIFFERENTIAL IMMUNOASSAY FOR ENDOGENOUS AND EXOGENOUS INSULIN*
Authors: Ellis Samols, Jill A. Ryder
Journal: Journal of Clinical Investigation (1961)

Preparation of insulin-I"31.Since a minute amount of insulin-I' serves as a tracer in the immunological sys- tem, it is essential to use a preparation with a high spe- cific activity so that the counting rate may be adequate.Recently we have found that this estimate agrees satis- factorily with our own finding of 5.61 U per mg (SE, 0.58), using as a standard for comparison a pure human insulin.2These results are to be reported in full else- where.All dilutions of insulin and antiserum were made in 0.1 ionic strength veronal buffer containing 0.25 per cent
Left ventricular surface tissue oxygen pressures determined by oxygen sensitive multiwire electrodes in pigs
Authors: P. F Conzen, H. Habazettl, M. Christ, H. Baier, J. Hobbhahn, B. Vollmar, K. Peter
Journal: Cardiovascular Research (1991)

Polarographic oxygen sensitive electrodes can be used to measure tissue oxygen pressures on the surface of the beating heart. The purpose of the study was to clarify the significance of these PO2 determinations.Changes in left ventricular surface oxygen pressures, subendocardial or subepicardial wall functions (ultrasonic dimension technique), and blood flow (radioactive microsphere technique) were correlated during different degrees of acute coronary artery stenoses in pigs.19 anaesthetised open chest pigs, 28-40 kg body weight, were studied during different degrees of constriction of the left anterior descending artery which did not influence overall left ventricular function or irreversibly damage the myocardium.Highly significant (p less than 0.001) correlations (each % delta) were obtained for surface tissue oxygen pressures (y) with subepicardial (y = 0.002 e 0.10x; r = 0.89) and subendocardial (y = 1.44 e 0.04x; r = 0.98) blood flow values, as well as with subendocardial function (y = 82.4 + 0.22x; r = 0.89); a significant correlation was also obtained for subendocardial function (y) with subendocardial blood flow (y = 66.0 + 0.28x; r = 0.69). However, no significant correlation was obtained for polarographic tissue PO2 with subepicardial segment function, indicating that regional function was maintained when tissue PO2 recordings were not much above 0 kPa and when blood flow was reduced by 25 to 30%.Oxygen pressures of the superficial layers of the left ventricle are relatively high at normal values of oxygen consumption but decrease rapidly if blood supply is reduced. Regional wall function is preserved at low oxygen pressures. Polarographic surface PO2 electrodes hence can be used to study influences of experimental interventions on oxygenation of the normally perfused and of the moderately ischaemic myocardium.
Peripheral Binding and Transport of the Thyroid Hormones.
Authors: S. H. Ingbar
Journal: Annals of Internal Medicine (1963)

s1 April 1963Peripheral Binding and Transport of the Thyroid Hormones.S. H. Ingbar, M.D.S. H. Ingbar, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-718_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe past decade has brought increasing recognition of the role played by peripheral transport mechanisms in the regulation of thyroid hormone economy. Electrophoretic studies of serum have revealed the presence of 2 proteins, thyroxine-binding globulin (TBG) and thyroxine-binding pre-albumin (TBPA), which together bind all but a small fraction of the thyroxine in the blood. Protein-bound thyroxine is in equilibrium with a very low concentration of "free" or unbound thyroxine. The concentration of the latter varies inversely with the binding activities of TBG and TBPA and directly with the total concentration of hormone in the blood. Considerable evidence suggests that bound... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass. (BS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 718-719KeywordsAttentionBloodGlobulinsHormonesProteinsSerum proteinsThyroid hormonesThyroxine Issue Published: 1 April 1963 PDF DownloadLoading ...
POSITRON EMISSION TOMOGRAPHY (PET) IN A COMMUNITY HOSPITAL: CLINICAL APPLICATIONS
Authors: J. L. Prather, W. T. Harris, D. W. Weiss, B. R. Bearden, K. W. Goad, K. L. Holman
Journal: Clinical Nuclear Medicine (1996)

Prather, J.; Harris, W. T.; Weiss, D. W.; Bearden, B. R.; Goad, K. W.; Holman, K. L. Author Information