tbuckley/cabot-search huggingface dataset:
Detection of Pathologic Prion Protein in the Olfactory Epithelium in Sporadic Creutzfeldt–Jakob Disease
Authors: Gianluigi Zanusso, Sergio Ferrari, Franco Cardone, Paolo Zampieri, Matteo Gelati, Michele Fiorini, Alessia Farinazzo, Marina Gardiman, Tiziana Cavallaro, Marina Bentivoglio, Pier Giorgio Righetti, Maurizio Pocchiari, Nicola Rizzuto, Salvatore Monaco
Journal: New England Journal of Medicine (2003)

Olfactory cortexes and the olfactory tracts are involved in sporadic Creutzfeldt–Jakob disease. We examined peripheral regions of the olfactory sensory pathway, including the olfactory mucosa, to assess whether pathologic infectious prion protein (PrPSc) is deposited in the epithelium lining the nasal cavity.
Taking a stand
Authors: Fiona Godlee
Journal: BMJ (2006)

The World Health Organization has had good and bad leaders. Dr Lee Jong-wook, who died last week just three years into his first term as WHO's director general, was one of the better ones (p 1234). He died just before the opening session of WHO's annual assembly and only days after the successful resolution of a cause he had championed—the registration of clinical trials (p 1232). His support, both moral and financial, for trial registration showed his willingness to resist pressure from powerful industry lobbies. Because of this, WHO's stance on trial registration should take its place alongside the organisation's earlier triumphs, …
Fourth Pan-American Medical Congress.
Authors: Ramon Guiteras
Journal: JAMA (1904)

A New Forgery Scheme.-Theprofession should be warned concerning a clever forger who has been cashing bad checks in Minneapolis.The man's scheme is novel and so far has proved successful.He writes a prescription and signs some well-known physician's name to it.This he takes to a drug store to be filled.In payment he tenders a check, usually for a small amount, and is usually given the change in cash.The man secured the blanks by telling a downtown druggist that he was a physician recently admitted to practice.His manners and appearance are good and few would take him for a crook.The
Single intubation test for investigation of malabsorption and diarrhoea.
Authors: R H Taylor, S Waterman
Journal: Gut (1983)

A one session multipurpose intubation method for the investigation of diarrhoea and malabsorption is described. It enables tests for bacterial colonisation, infestations, and luminal cytology of the small intestine to be combined with a pancreatic exocrine function test and a jejunal biopsy during the same intubation. The technique has proved acceptable, reliable, diagnostically valuable, and convenient for use on outpatients.
Platelet membrane glycoproteins implicated in ristocetin-induced aggregation. Studies of the proteins on platelets from patients with Bernard-Soulier syndrome and von Willebrand's disease.
Authors: C S Jenkins, D R Phillips, K J Clemetson, D Meyer, M J Larrieu, E F Lüscher
Journal: Journal of Clinical Investigation (1976)

The antibiotic ristocetin only aggregates platelets in the presence of plasma von Willebrand factor. Platelets from patients with Bernard-Soulier syndrome do not aggregate upon addition of ristocetin although, in contrast to von Willebrand's disease, plasma levels of factor VIII complex (factor VIII clotting activity, von Willebrand factor activity, and von Willebrand antigen) are normal. The membrane surface of normal platelets was modified and compared to the surface of platelets from a patient with Bernard-Soulier syndrome in an attempt to identify the receptor involved in von Willebrand factor-ristocetin-induced aggregation. After the incubation of washed normal platelets with a preparation of ristocetin previously shown to contain a proteolytic contaminant, the aggregation response is significantly decreased on addition or normal plasma. Analaysis by gel electrophoresis of such platelets when stained for carbohydrate revealed a decrease in the relative amounts of membrane glycopro-eins. Chymotrypsin-treated normal platelets had less membrane glycoproteins in addition to giving a reduced aggregation response in ristocetin-induced aggregation. Staining of gels for protein and carbohydrate indicated that there was an extensive change in the surface of Bernard-Soulier platelets, whereas those from patients with von Willebrand's disease appeared the same as normal. Platelets from patients were labeled by the lactoperoxidase iodination technique. Not only was the relative intensity of staining of platelet-specific proteins and glycoproteins changed in Bernard-Soulier platelets, but the iodination of the glycoproteins on the membrane surface relative to other membrane constituents was lower. In contrast, platelets from patients with von Willebrand's disease showed a normal exposure of membrane components. These data suggest therefore that membrane glycoproteins may play a functional role in ristocetin-induced aggregation.
Association of Acromegaly and Meningiomas
Authors: Elaine M. Bunick
Journal: JAMA (1978)

THE SIMULTANEOUS occurrence of an intracranial meningioma and a pituitary adenoma is exceedingly rare, with only six cases previously reported.<sup>1-2</sup>In two of those cases, both tumors were present before therapy. Since the meningiomas developed after radiation therapy in the other four cases, the possibility must be considered that growth hormoneproducing pituitary tumors facilitate the development of meningiomas. We report the coexistence of a growth hormone-producing pituitary tumor and a subfrontal meningioma at the time of initial diagnosis. <h3>Report of a Case</h3> A 57-year-old man was admitted to Hahnemann Medical College and Hospital for evaluation of an abnormal skull roentgenogram and acromegalic features. The patient had intermittent right-sided headaches unaccompanied by change in vision, nausea, or vomiting precipitated by anxiety. For many years, these were promptly relieved by acetaminophen. Though his hands had always been large, his feet had increased in size during the years. He denied any change
Capsaicin-induced airway obstruction in tracheally perfused guinea pig lungs.
Authors: C M Lilly, G Besson, E Israel, I W Rodger, J M Drazen
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The neurokinin receptors responsible for transducing the airway obstruction resulting from capsaicin infusion were defined in the tracheally perfused guinea pig lung. In this lung preparation, buffer is perfused via the trachea and allowed to exit the lung through numerous small holes in the pleural surface; airway obstruction is monitored as the backpressure (Pao) generated at a constant perfusion flow rate. Infusion of the specific NK1 receptor agonist, Sar-9 Met02(11) substance P, resulted in an increase in Pao; this effect was prevented by the NK1 receptor antagonist CP 99,994 but not by the NK2 receptor antagonist SR 48,968. Infusion of the specific NK2 receptor agonist Nle10-neurokinin A 4-10 resulted in an increase in Pao; this effect was prevented by the NK2 receptor antagonist SR 48,968 but not by the NK1 receptor antagonist CP 99,994. In the absence of NK receptor antagonists, infusion of capsaicin resulted in a significant increase in Pao, 31 +/- 4 cm H2O. In the presence of the NK1 receptor antagonist, the capsaicin response was not diminished, but in the presence of the NK2 receptor antagonist, the Pao response diminished to only 10 +/- 2 cm H2O, p < 0.001. These data indicate that when capsaicin is presented to the epithelial surface of the lung the resulting airway obstruction is mediated predominantly by NK2 receptor stimulation.
Improved glucose control in maturity-onset diabetes treated with high-carbohydrate-modified fat diet.
Authors: R W Simpson, J I Mann, J Eaton, R A Moore, R Carter, T D Hockaday
Journal: BMJ (1979)

Fourteen patients with established maturity-onset diabetes were treated as outpatients with a high-carbohydrate-(about 60% of total daily energy requirements)-modified fat diet (ratio of polyunsaturated fatty acids to other fatty acids greater than or equal to 1:1) for six weeks. Commercially available and acceptable cereal foods and tuberous vegetables high in both digestible and non-digestible carbohydrates were used. Simple sugars were restricted. Compared with their usual, low-carbohydrate diabetic diet this diet resulted in a fall in basal plasma glucose concentration (average of values measured at 0300, 0500, and 0700), mean preprandial plasma glucose concentration (average of values measured at 0800, 1230, and 1730), and percentage of glycosylated haemoglobin. Modifying dietary fat also decreased the fasting plasma cholesterol concentration. The findings suggest that it is no longer justifiable to prescribe a low-carbohydrate diet for maturity-onset diabetes.
TRAIL/Apo2L Mediates the Release of Procoagulant Endothelial Microparticles Induced by Thrombin In Vitro
Authors: Stéphanie Simoncini, Makon-Sébastien Njock, Stéphane Robert, Laurence Camoin-Jau, José Sampol, Jean-Robert Harlé, Catherine Nguyen, Françoise Dignat-George, Francine Anfosso
Journal: Circulation Research (2009)

Microparticles are small vesicles playing a crucial role in cell communication by promoting prothrombotic and proinflammatory responses. However, the molecular mechanisms underlying their release are still elusive. We previously established that thrombin promoted the generation of endothelial microparticles (EMPs). In the present study, gene profiling identified TRAIL/Apo2L, a cytokine belonging to the tumor necrosis factor-alpha superfamily, as a target of thrombin. Thrombin increased the expression of cell-associated and soluble forms of TRAIL (sTRAIL) in HMEC-1 cells and human umbilical vein endothelial cells (HUVECs). Blocking TRAIL by specific antibodies or by small interfering RNA reduced both the number and the procoagulant activity of EMPs released by thrombin. Consistent with an involvement of sTRAIL in thrombin-induced EMP release, we showed that (1) exogenously added sTRAIL generated procoagulant EMPs; (2) supernatants from thrombin-stimulated endothelial cells induced EMP release by HMEC-1 cells and HUVECs, whereas those recovered from TRAIL knockdown endothelial cells displayed no effect. TRAIL/TRAIL-R2 complex mediated EMP release by initiating the recruitment of adaptor proteins and the activation of nuclear factor kappaB. Moreover, sTRAIL modulated intercellular adhesion molecule-1 and interleukin-8 expression induced by thrombin by a downstream pathway involving nuclear factor kappaB activation. Our data reveal a novel mechanism controlling EMP release and identify TRAIL as a key partner in the pathway linking coagulation and inflammation elicited by thrombin.
Insulin Concerns and Promises
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2011)

At a symposium discussing controversies pertaining to relationships between diabetes and cancer, Jeffrey A. Johnson (Edmonton, Canada) reviewed epidemiologic data, beginning with a meta-analysis showing that diabetes is associated with increased rates of cancers of the pancreas, colon and rectum, bladder, liver, and breast; endometrial cancer; and non-Hodgkin's lymphoma. Prostate cancer rates are decreased, perhaps as a consequence of a subtle form of hypogonadism, but prostate cancer mortality is increased among diabetic men who do develop prostate cancer. Obesity increases the development of cancers as well, to a greater degree with greater levels of obesity, particularly for cancers of the esophagus and thyroid and, among women, cancers of the endometrium, gallbladder, colon, and kidney. Cancer mortality increases by ∼50% in both sexes in association with obesity (1). The interesting exception to the generally adverse association of obesity with malignancy is its negative relationship with lung cancer, with cigarette use the presumed confounder by its weight-reducing effect (2).

The mechanism of the relationship between diabetes and cancer has not been defined in clinical studies. Johnson's meta-analysis of trials of glycemic control did not show an effect on the risk of developing malignancy (3). Hyperglycemia was, however, associated with cancer mortality in 10-year studies of >1 million Korean (4) and >500,000 European (5) men and women, with the studies controlling for obesity though possibly reflecting a role of hyperinsulinemia. A role of hyperinsulinemia is further suggested by studies showing association of C-peptide with colorectal cancer risk (6,7). Reduced cancer survival seen in individuals with diabetes (8) may be, at least to an extent, due to diabetes-related diseases other than the malignancy itself (9) or to diabetic individuals having a lower likelihood of undergoing mammography, resulting in presentation with later-stage tumors (10). Lower rates of Pap test screening for cervical …
A simple technique to aid intubation of the duodenoscope in the afferent limb of Billroth II gastrectomies for endoscopic retrograde cholangiopancreatography
Authors: J. García-Cano
Journal: Endoscopy (2008)

Billroth II gastrectomy poses a challenge for the endoscopist performing endoscopic retrograde cholangiopancreatography (ERCP). The papilla appears in a reversed position in the endoscopic view, making cannulation more difficult ([Fig. 1], [2]). The initial problem usually encountered is that of finding the afferent loop and advancement of the duodenoscope to the papillary area. Negotiating the stoma and the afferent limb is a recognized cause of bowel perforation [1] [2]. The use of forward-viewing endoscopes can be sometimes helpful for ERCP in these patients [3], and perforation has rarely been reported when these instruments are used. Nevertheless, some of the duodenoscope’s properties (e. g. the elevator) are sometimes necessary for biliary or pancreatic interventions in patients with Billroth II gastrectomies. A simple technique for reaching the papillary area in patients with this type of gastrectomy is described here.
The golden age of the placebo
Authors: C. Brewer
Journal: BMJ (2012)

The first general practice locum I did was in a large Yorkshire village. I soon got to know the local pharmacist, whose family had owned the business for three generations. Among the Victorian devices in the back of his shop was a small, lidded box about 5 cm square. The pharmacist drew my attention to traces of gold in the corners; it was a device for coating placebo pills with a thin layer of gold dust. Their price could then …
Biological markers during early pregnancy: trophoblastic signals of the peri-implantation period.
Authors: S R Glasser, J Julian, M I Munir, M J Soares
Journal: Environmental Health Perspectives (1987)

The peri-implantation period extends from the time the blastocyst is free in the uterus, through the processes of recognition and attachment, to the beginning of trophoblast differentiation and the interactions between the embryo and the uterine endometrium which initiate establishment of the hemochorial placenta. It is during the peri-implantation period that the embryo and hormonally regulated endometrial cells appear to be most sensitive to factors which introduce risk into the intrauterine environment. There are no markers which can be used practically to assess pregnancy risk during the peri-implantation period of either human or laboratory rodents. Experimental studies, using in vitro laboratory models of differentiating trophoblast cells, have identified peptide hormone markers of pivotal developmental processes. Exposure of trophoblast during the expression of these processes could have severe and far-reaching effects individually and societally. While these trophoblast signals are limited in their utility with respect to health monitoring extrapolation of these findings to human pregnancy, the signals could serve to identify more practical and sensitive markers to assess risk in early gestation. Human chorionic gonadotropin (hCG) has been used extensively as a marker to assess risk during the early stages of pregnancy. Extrapolation of experimental data indicates how hCG could be used more effectively in analyses of possible cause and effect relationships. The limitations of hCG as a marker for risk during the human peri-implantation period are discussed. Peptide hormones which could serve to assess risk during this critical period of extraordinary sensitivity to toxic factors are introduced.
Training induced physiological and metabolic changes associated with improvements in running performance.
Authors: R Ramsbottom, C Williams, N Fleming, M L Nute
Journal: British Journal of Sports Medicine (1989)

The purpose of the present study was to examine the relationship between improvements in running performance and some of the prominent physiological and metabolic adaptations to endurance exercise training. Twelve male undergraduates agreed to participate in this study (trial group), aged matched physical education students provided a control group. Running performance, assessed as a five km time trial, improved from 19.69 +/- 2.24 to 19.22 +/- 2.03 min in the trial group (P less than 0.01) after training. Maximal oxygen uptake values increased from 56.0 +/- 6.1 to 60.7 +/- 5.4 ml.kg-1.min-1, the running speed equivalent to a blood lactate reference concentration of 4 mmol.l-1 (V-4 mM) increased from 3.79 +/- 0.77 to 4.04 +/- 0.71 m.s-1, and the rate of oxygen consumption at 3.58 m.s-1 (running economy) increased from 43.3 +/- 3.2 to 45.0 +/- 3.4 ml.kg-1.min-1 (P less than 0.01). The control group did not show any significant changes. The improved five km times in the trial group were significantly correlated (r = -0.71; P less than 0.01) with changes in the running economy rather than changes in the VO2 max (r = -0.07; ns), or V-4 mM (r = -0.13; ns) suggesting the increased rate of oxygen utilization reflected a greater oxidative degradation of metabolic substrates together with a slower rate of lactate production.
Abstract 4631: Anti-CD70 antibody-drug conjugates containing pyrrolobenzodiazepine dimers demonstrate robust antitumor activity
Authors: Scott Jeffrey, Patrick Burke, David Meyer, Robert Lyon, Jamie Miyamoto, Martha Anderson, Ivan Stone, Che-Leung Law, Peter Senter
Journal: Cancer Research (2012)

Abstract Antibody-drug conjugates (ADCs) represent an important approach for the selective delivery of highly potent small molecules to malignant cells. Recently, we have adapted the highly cytotoxic class of minor groove DNA crosslinking agents, pyrrolobenzodiazepine dimers (PBDs), in order to conjugate them to monoclonal antibodies. These totally synthetic molecules alkylate guanine bases in a sequence-specific manner to cause cell death at pM concentrations. In this report, we describe for the first time a novel PBD that can be stably conjugated to the anti-CD70 monoclonal antibody (mAb) h1F6 via maleimide conjugation to engineered cysteine residues created by the single amino acid substitution S239C on each heavy chain. This results in a uniform loading of two drugs per antibody. The resulting ADC binds selectively to CD70 on renal cell carcinoma cell lines and releases the free drug upon internalization and cleavage of the dipeptide linker in the lysosome. The ADC retains the robust cytotoxicity of the free drug, displaying immunologically selective antitumor activity in xenograft models at well tolerated doses as low as 0.1 mg/kg. The PBDs represent a promising new class of cancer drugs for targeted delivery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4631. doi:1538-7445.AM2012-4631
A Randomized Trial of Diagnostic Strategies after Normal Proximal Vein Ultrasonography for Suspected Deep Venous Thrombosis: <scp>d</scp>-Dimer Testing Compared with Repeated Ultrasonography
Authors: Clive Kearon, Jeffrey S. Ginsberg, James Douketis, Mark A. Crowther, Alexander G. Turpie, Shannon M. Bates, Agnes Lee, Patrick Brill-Edwards, Terri Finch, Michael Gent
Journal: Annals of Internal Medicine (2005)

Background: With suspected deep venous thrombosis and normal results on proximal vein ultrasonography, a negative d-dimer result may exclude thrombosis and a positive d-dimer result may be an indication for venography. Objective: To evaluate and compare the safety of 2 diagnostic strategies for deep venous thrombosis. Design: Randomized, multicenter trial. Setting: Four university hospitals. Patients: 810 outpatients with suspected deep venous thrombosis and negative results on proximal vein ultrasonography. Interventions: Erythrocyte agglutination d-dimer testing followed by no further testing if the result was negative and venography if the result was positive (experimental) or ultrasonography repeated after 1 week in all patients (control). Measurements: Symptomatic deep venous thrombosis diagnosed initially and symptomatic venous thromboembolism during 6 months of follow-up. Results: Nineteen of 408 patients (4.7%) in the d-dimer group and 3 of 402 patients (0.7%) in the repeated ultrasonography group initially received a diagnosis of deep venous thrombosis (P < 0.001). During follow-up of patients without a diagnosis of deep venous thrombosis on initial testing, 8 patients (2.1% [95% CI, 0.9% to 4.0%]) in the d-dimer group and 5 patients (1.3% [CI, 0.4% to 2.9%]) in the repeated ultrasonography group developed symptomatic venous thromboembolism (difference, 0.8 percentage point [CI, −1.1 to 2.9 percentage points]; P > 0.2). Venous thromboembolism occurred in 1.0% (CI, 0.2% to 2.8%) of those with a negative d-dimer result. Limitations: Seventy patients (8.6%) deviated from the diagnostic protocols, and 9 patients (1.1%) had inadequate follow-up. Conclusion: In outpatients with suspected deep venous thrombosis who initially had normal results on ultrasonography of the proximal veins, a strategy based on d-dimer testing followed by no further testing if the result was negative and venography if the result was positive had acceptable safety and did not differ from the safety of a strategy based on withholding anticoagulant therapy and routinely repeating ultrasonography after 1 week.