tbuckley/cabot-search huggingface dataset:
Inhalational anthrax in a vaccinated soldier
Authors: Annemarie Sykes, Tim Brooks, Michael Dusmet, Andrew G. Nicholson, David M. Hansell, Robert Wilson
Journal: European Respiratory Journal (2013)

To the Editor: 

The spore-forming bacterium, Bacillus anthracis , primarily affects herbivores but can manifest as cutaneous (>95% of cases), gastrointestinal or pulmonary infection in humans. Pulmonary anthrax, resulting from inhalation of anthrax spores, is rapidly progressive and historically was considered to be invariably fatal. Clinical features include haemorrhagic thoracic lymphadenitis, pulmonary oedema, pleural effusions, leptomeningeal involvement, septic shock and respiratory distress, with death often following within 24 h [1, 2].

Due to the high mortality and potential for use as a biological agent, anthrax vaccines were developed in the 1950s [3]. B. anthracis is composed of three proteins known as protective antigen (PA), oedema factor and lethal factor (LF), with PA named after its ability to provide experimental immunity. Anthrax vaccines demonstrated protection against cutaneous anthrax in tannery workers [3] and vaccination protected rhesus monkeys from inhalational anthrax for up to 2 years [4]. No adequately powered studies exist that demonstrate protection by the vaccine against inhalational anthrax in humans. Despite this, widespread vaccination of military personnel was undertaken by allied forces during the recent Gulf Wars [5].

We present a case of initially unrecognised, inhalational anthrax in a vaccinated member of the armed forces.

A 38-year-old male presented with severe, sudden-onset central chest pain at rest, which was associated with nausea and dizziness. He denied shortness of breath. His past medical history included a “supraclavicular lymph node infection” aged 18 years. He was previously fit and well, apart from an undiagnosed painful right knee sustained in the …
Allogeneic Bone Marrow Transplantation, Zidovudine, and Human Immunodeficiency Virus Type 1 (HIV-I) Infection
Authors: Holland Hk, Saral R, Rossi Jj, Donnenberg Ad, Burns Wh, Beschorner We, Farzadegan H, Jones Rj, Quinnan Gv, Vogelsang Gb
Journal: Annals of Internal Medicine (1989)

Human immunodeficiency virus type 1 (HIV-1)-infected patients with non-Hodgkin lymphoma are classified as having the acquired immunodeficiency syndrome (AIDS). Allogeneic bone marrow transplantation is a successful therapy for patients with lymphoma who have a poor prognosis. Combined therapy with allogeneic bone marrow transplantation and the antiviral drug zidovudine has the potential advantage of protecting the new donor hematopoietic-lymphoid and monocyte-macrophage cells from HIV-1 infection. A 41-year-old man infected with HIV-1 who had lymphoma was treated with high-dose cyclophosphamide and total body irradiation followed by allogeneic bone marrow transplantation. Before transplantation he received high-dose zidovudine for 2 weeks (5 mg/kg body weight intravenously every 4 hours) and after transplantation he received a lower maintenance dose (1.33 mg/kg body weight intravenously every 4 hours). No untoward toxicities attributable to zidovudine were observed. Bone marrow engraftment occurred on day 17. Chromosome and restriction fragment length polymorphism analyses demonstrated complete chimerism. Peripheral blood mononuclear cells and bone marrow samples were negative for HIV-1 by culture and polymerase chain reaction gene amplification 32 days after transplantation. The patient died 47 days after transplantation because of tumor relapse. Analysis of autopsy tissue showed no evidence of HIV-1 by either culture (brain, bone marrow, lymph node, and tumor specimens) or by polymerase chain reaction gene amplification for HIV-1 RNA and DNA sequences (brain, bone marrow, heart, kidney, liver, lung, rectosigmoid, spleen, and tumor specimens). Immunologic monitoring showed loss of HIV-1 antibody. Adoptive immunologic transfer was shown to be present to both tetanus and diphtheria antigens. Our case suggests that the HIV-1-infected recipient cells may have been eradicated secondary to the bone marrow ablative chemo-radiotherapy and that zidovudine may be able to prevent the establishment of HIV-1 infection in donor hematopoietic-lymphoid cells.
Proinflammatory Adaptive Cytokine and Shed Tumor Necrosis Factor Receptor Levels Are Elevated Preceding Systemic Lupus Erythematosus Disease Flare
Authors: Melissa E. Munroe, Evan S. Vista, Joel M. Guthridge, Linda F. Thompson, Joan T. Merrill, Judith A. James
Journal: Arthritis & Rheumatology (2014)

Objective Systemic lupus erythematosus (SLE) is a multifaceted disease characterized by immune dysregulation and unpredictable disease activity. This study sought to evaluate the changes in plasma concentrations of soluble mediators that precede clinically defined disease flares. Methods Fifty‐two different soluble mediators, including cytokines, chemokines, and soluble receptors, were examined using validated multiplex bead‐based or enzyme‐linked immunosorbent assays in plasma from 28 European American patients with SLE who developed disease flare 6 or 12 weeks after a baseline assessment (preflare), 28 matched SLE patients without impending flare (nonflare), and 28 matched healthy controls. In a subset of 13 SLE patients, mediators within samples obtained preceding disease flare were compared with those within samples from the same individual obtained during a clinically stable period without flare. Results Compared to SLE patients with clinically stable disease, SLE patients with impending flare had significant alterations ( P ≤ 0.01) in the levels of 27 soluble mediators at baseline; specifically, the levels of proinflammatory mediators, including Th1‐, Th2‐, and Th17‐type cytokines, were significantly higher several weeks before clinical flare. Baseline levels of regulatory cytokines, including interleukin‐10 and transforming growth factor β, were higher in nonflare SLE patients, whereas baseline levels of soluble tumor necrosis factor receptor type I (TNFRI), TNFRII, Fas, FasL, and CD40L were significantly higher ( P ≤ 0.002) in preflare SLE patients. The normalized and weighted combined soluble mediator score was significantly higher ( P ≤ 0.0002) in preflare samples from SLE patients compared to samples from the same patients obtained during periods of stable disease. Conclusion The levels of proinflammatory adaptive cytokines and shed TNF receptors are elevated prior to disease flare, while the levels of regulatory mediators are elevated during periods of stable disease. Alterations in the balance between inflammatory and regulatory mediators may help identify patients at risk of disease flare and help decipher the pathogenic mechanisms of SLE.
Dysregulation of Peripheral and Central Chemoreflex Responses in Chagas’ Heart Disease Patients Without Heart Failure
Authors: José Augusto Soares Barreto-Filho, Fernanda Marciano Consolim-Colombo, Heno Ferreira Lopes, Carlos Roberto Martins Sobrinho, Grazia M. Guerra-Riccio, Eduardo Moacyr Krieger
Journal: Circulation (2001)

Background The peripheral and central chemoreflexes are important autonomic mechanisms for regulating breathing and cardiovascular function. Although pathological inflammatory infiltration of the peripheral chemoreceptors and central nervous system has been reported in Chagas’ disease, functional evaluation of chemoreflexes has not yet been performed. Methods and Results The hypothesis that chemoreflex function is altered in patients with Chagas’ heart disease (CH) but normal left ventricle function was tested in 12 CH patients and 13 matched control subjects. The ventilatory rate, minute ventilation, heart rate, mean arterial pressure, forearm blood flow, forearm vascular resistance, and venous norepi-nephrine responses to hypoxia and hypercapnia were determined. During hypoxia, the decrease in oxygen saturation was smaller in CH patients, despite a similar ventilatory response between groups. Both groups showed an increase in heart rate during hypoxia, but this response was blunted in CH patients. Although the mean arterial pressure response to hypoxia was similar in both groups, forearm vascular resistance significantly decreased in control subjects while remaining unchanged in CH patients. Moreover, a significant increase in plasma norepinephrine levels elicited by stimulation of peripheral chemoreceptors was observed only in the CH group. During hypercapnia, the increase in minute ventilation was smaller in CH patients, who did not exhibit the increase in norepinephrine observed in control subjects. Conclusions These data suggest that CH potentiates respiratory, cardiovascular, and autonomic responses to peripheral chemoreceptor activation by hypoxia in patients with normal left ventricular function. The ventilatory and sympathetic responses to central chemoreceptor activation by hypercapnia, however, are significantly blunted.
Increased faecal mucin sulphatase activity in ulcerative colitis: a potential target for treatment.
Authors: H H Tsai, A D Dwarakanath, C A Hart, J D Milton, J M Rhodes
Journal: Gut (1995)

Colonic mucin is heavily sulphated and it has been shown that enzymatic desulphation by faecal bacterial sulphatases greatly increases its susceptibility to degradation by faecal glycosidases. A possible role for faecal mucin sulphatase in the pathogenesis of inflammatory bowel disease has therefore been explored. Faecal mucin sulphatase activity assayed using 35S mucin as substrate was increased in ulcerative colitis (median 80.2 units/g pellet weight (range 6.9-1063; 95% confidence intervals (CI): 45.2 to 293.8, n = 22) compared with 11.3 units/g (range 3.0-53.5; 95% CI: 8.7 to 29.8, n = 17) in healthy controls (p &lt; 0.01), where one unit released 1000 dpm free sulphate/hour from 35S mucin (1680 dpm/microgram). Patients with active ulcerative colitis had higher sulphatase activity (median 146; 95% CI: 98 to 253 units/g, n = 10) than those with inactive ulcerative colitis (median 42.2; CI: 22.5 to 81.6 units/g, n = 12) (p &lt; 0.05). Longitudinal studies in patients with ulcerative colitis show fluctuations of faecal mucin sulphatase activity corresponding to clinical disease activity in six of seven patients. Faecal mucin sulphatase activity was not significantly increased in Crohn9s disease (median 36.6, range 5.7-106.6; 95% CI: 22.9 to 65.3 units/g, n = 14). The bismuth salts, bismuth subcitrate and bismuth subsalicylate were found to inhibit faecal mucin sulphatase activity at concentrations achievable therapeutically. The increased faecal mucin sulphatase activity in ulcerative colitis could be the result of greater intraluminal substrate (mucin) availability leading to bacterial enzyme induction, but would probably result in more rapid degradation of secreted mucin and represents a potential target for treatment.
Acute hamstring injuries in Swedish elite sprinters and jumpers: a prospective randomised controlled clinical trial comparing two rehabilitation protocols
Authors: Carl M Askling, Magnus Tengvar, Olga Tarassova, Alf Thorstensson
Journal: British Journal of Sports Medicine (2014)

Background Hamstring strain is a common injury in sprinters and jumpers, and therefore time to return to sport and secondary prevention become of particular concern. Objective To compare the effectiveness of two rehabilitation protocols after acute hamstring injury in Swedish elite sprinters and jumpers by evaluating time needed to return to full participation in the training process. Study design Prospective randomised comparison of two rehabilitation protocols. Methods Fifty-six Swedish elite sprinters and jumpers with acute hamstring injury, verified by MRI, were randomly assigned to one of two rehabilitation protocols. Twenty-eight athletes were assigned to a protocol emphasising lengthening exercises, L-protocol, and 28 athletes to a protocol consisting of conventional exercises, C-protocol. The outcome measure was the number of days to return to full training. Re-injuries were registered during a period of 12 months after return. Results Time to return was significantly shorter for the athletes in the L-protocol, mean 49 days (1SD±26, range 18–107 days), compared with the C-protocol, mean 86 days (1SD±34, range 26–140 days). Irrespective of protocol, hamstring injuries where the proximal free tendon was involved took a significantly longer time to return than injuries that did not involve the free tendon, L-protocol: mean 73 vs 31 days and C-protocol: mean 116 vs 63 days, respectively. Two reinjuries were registered, both in the C-protocol. Conclusions A rehabilitation protocol emphasising lengthening type of exercises is more effective than a protocol containing conventional exercises in promoting time to return in Swedish elite sprinters and jumpers.
Laser Treatment of Benign Prostatic Obstruction: Basics and Physical Differences
Authors: Thorsten Bach, Rolf Muschter, Roland Sroka, Stavros Gravas, Andreas Skolarikos, Thomas R.W. Herrmann, Thomas Bayer, Thomas Knoll, Claude-Clément Abbou, Guenter Janetschek, Alexander Bachmann, Jens J. Rassweiler
Journal: European Urology (2011)
In Vivo Molecular Imaging of Acute and Subacute Thrombosis Using a Fibrin-Binding Magnetic Resonance Imaging Contrast Agent
Authors: René M. Botnar, Alexandra S. Perez, Sonia Witte, Andrea J. Wiethoff, James Laredo, James Hamilton, William Quist, Edward C. Parsons, Anand Vaidya, Andrew Kolodziej, John A. Barrett, Philip B. Graham, Robert M. Weisskoff, Warren J. Manning, Michael T. Johnstone
Journal: Circulation (2004)

Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis.Fifteen male New Zealand White rabbits (weight, approximately 3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell's viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as "hot spots" after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology.We demonstrate the feasibility of in vivo "molecular" MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke.
Randomised controlled trial of prevention of falls in people aged ≥75 with severe visual impairment: the VIP trial
Authors: A John Campbell, M Clare Robertson, Steven J La Grow, Ngaire M Kerse, Gordon F Sanderson, Robert J Jacobs, Dianne M Sharp, Leigh A Hale
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision. <b>Design</b> Randomised controlled trial. <b>Setting</b> Dunedin and Auckland, New Zealand. <b>Participants</b> 391 women and men aged ≥(1) 75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up. <b>Interventions</b> Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96). <b>Main outcome measures</b> Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme. <b>Results</b> Fewer falls occurred in the group randomised to the home safety programme but not in the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost $NZ650 (£234, 344 euros, $US432) (at 2004 prices) per fall prevented. <b>Conclusion</b> The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence. <b>Trial registration number</b>ISRCTN15342873.
Seven Transmembrane Receptors as Shapeshifting Proteins: The Impact of Allosteric Modulation and Functional Selectivity on New Drug Discovery
Authors: Terry Kenakin, Laurence J. Miller
Journal: Pharmacological Reviews (2010)

It is useful to consider seven transmembrane receptors (7TMRs) as disordered proteins able to allosterically respond to a number of binding partners. Considering 7TMRs as allosteric systems, affinity and efficacy can be thought of in terms of energy flow between a modulator, conduit (the receptor protein), and a number of guests. These guests can be other molecules, receptors, membrane-bound proteins, or signaling proteins in the cytosol. These vectorial flows of energy can yield standard canonical guest allostery (allosteric modification of drug effect), effects along the plane of the cell membrane (receptor oligomerization), or effects directed into the cytosol (differential signaling as functional selectivity). This review discusses these apparently diverse pharmacological effects in terms of molecular dynamics and protein ensemble theory, which tends to unify 7TMR behavior toward cells. Special consideration will be given to functional selectivity (biased agonism and biased antagonism) in terms of mechanism of action and potential therapeutic application. The explosion of technology that has enabled observation of diverse 7TMR behavior has also shown how drugs can have multiple (pluridimensional) efficacies and how this can cause paradoxical drug classification and nomenclatures.
Plasma Ghrelin and Desacyl Ghrelin Concentrations in Renal Failure
Authors: Akihiro Yoshimoto, Kiyoshi Mori, Akira Sugawara, Masashi Mukoyama, Kensei Yahata, Takayoshi Suganami, Kazuhiko Takaya, Hiroshi Hosoda, Masayasu Kojima, Kenji Kangawa, Kazuwa Nakao
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Ghrelin is a novel hormone that possesses growth hormone (GH)–releasing, cardiovascular, and metabolic activities. Ghrelin is a unique acylated polypeptide, and the naked peptide, desacyl ghrelin, does not have the activity. This study examines plasma ghrelin concentrations in 41 patients with mild to severe renal diseases. Two kinds of radioimmunoassays were used: amino-terminal immunoreactivity represents ghrelin alone (N-IR), and carboxyl-terminal immunoreactivity corresponds to the sum of both ghrelin and desacyl ghrelin (C-IR). In all subjects, the plasma N-IR was much smaller than the C-IR, indicating that desacyl ghrelin predominates over ghrelin in the circulation. The plasma C-IR, but not N-IR, was significantly correlated with the serum creatinine level and was increased 2.8-fold in patients with end-stage renal disease compared with those in patients with normal renal function. The plasma GH concentration was significantly correlated with the plasma N-IR and the C-IR, as well as with the serum creatinine level. Bilateral nephrectomy in mice caused marked increase in the plasma C-IR without significant changes in the local C-IR and ghrelin mRNA level in the stomach, which is the main site of ghrelin production. These findings suggest that circulating ghrelin concentrations play a role in the regulation of blood GH concentrations and that the kidney is an important site for clearance and/or degradation of desacyl ghrelin. Furthermore, elevation of blood GH levels in renal failure seems to be caused by a mechanism other than alteration in the circulating ghrelin concentration.
Axillary recurrence in sentinel lymph node-negative breast cancer patients
Authors: P. Poletti, P. Fenaroli, A. Milesi, A. Paludetti, S. Mangiarotti, G. Virotta, E. Candiago, A. Bettini, E.R. Caremoli, R. Labianca, C. Tondini
Journal: Annals of Oncology (2008)
Digital image analysis of collagen assessment of progression of fibrosis in recurrent HCV after liver transplantation
Authors: Pinelopi Manousou, Andrew K. Burroughs, Emmanuel T. Sochatzis, Grazia Isgro, Andrew Hall, Anna Green, Vincenza Calvaruso, Guang Li Ma, Jeremy Gale, Gary Burgess, James O’Beirne, David Patch, Douglas Thorburn, Gioacchino Leandro, Amar Paul Dhillon
Journal: Journal of Hepatology (2012)
Lack of Methylthioadenosine Phosphorylase Expression in Mantle Cell Lymphoma Is Associated with Shorter Survival: Implications for a Potential Targeted Therapy
Authors: Silvia Marcé, Olga Balagué, Luis Colomo, Antonio Martinez, Sylvia Höller, Neus Villamor, Francesc Bosch, German Ott, Andreas Rosenwald, Lorenzo Leoni, Manel Esteller, Mario F. Fraga, Emili Montserrat, Dolors Colomer, Elias Campo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To determine the methylthioadenosine phosphorylase (MTAP) gene alterations in mantle cell lymphoma (MCL) and to investigate whether the targeted inactivation of the alternative de novo AMP synthesis pathway may be a useful therapeutic strategy in tumors with inactivation of this enzyme. Experimental Design: MTAP gene deletion and protein expression were studied in 64 and 52 primary MCL, respectively, and the results were correlated with clinical behavior. Five MCL cell lines were analyzed for MTAP expression and for the in vitro sensitivity to l-alanosine, an inhibitor of adenylosuccinate synthetase, and hence de novo AMP synthesis. Results: No protein expression was detected in 8 of 52 (15%) tumors and one cell line (Granta 519). Six of these MTAP negative tumors and Granta 519 cell line had a codeletion of MTAP and p16 genes; one case showed a deletion of MTAP, but not p16, and one tumor had no deletions in neither of these genes. Patients with MTAP deletions had a significant shorter overall survival (mean, 16.1 months) than patients with wild-type MTAP (mean, 63.6 months; P &amp;lt; 0.0001). l-Alanosine induced cytotoxicity and activation of the intrinsic mitochondrial-dependent apoptotic pathway in MCL cells. 9-β-d-Erythrofuranosyladenine, an analogue of 5′-methylthioadenosine, selectively rescued MTAP-positive cells from l-alanosine toxicity. Conclusions: MTAP gene deletion and lack of protein expression are associated with poor prognosis in MCL and might identify patients who might benefit from treatment with de novo AMP synthesis pathway–targeted therapies.