tbuckley/cabot-search huggingface dataset:
DAI (DLM-1/ZBP1) as a Genetic Adjuvant for DNA Vaccines That Promotes Effective Antitumor CTL Immunity
Authors: Alvaro Lladser, Dimitrios Mougiakakos, Helena Tufvesson, Maarten A Ligtenberg, Andrew FG Quest, Rolf Kiessling, Karl Ljungberg
Journal: Molecular Therapy (2010)

DNA vaccination is an attractive approach to induce antigen-specific cytotoxic CD8(+) T lymphocytes (CTLs), which can mediate protective antitumor immunity. The potency of DNA vaccines encoding weakly immunogenic tumor-associated antigens (TAAs) can be enhanced by codelivering gene-encoded adjuvants. Pattern recognition receptors (PRRs) that sense intracellular DNA could potentially be used to harness intrinsic immune-stimulating properties of plasmid DNA vaccines. Consequently, the cytosolic DNA sensor, DNA-dependent activator of interferon (IFN) regulatory factors (DAI), was used as a genetic adjuvant. In vivo electroporation (EP) of mice with a DAI-encoding plasmid (pDAI) promoted transcription of genes encoding type I IFNs, proinflammatory cytokines, and costimulatory molecules. Coimmunization with pDAI and antigen-encoding plasmids enhanced in vivo antigen-specific proliferation, and induction of effector and memory CTLs. Moreover, codelivery of pDAI effectively promoted CTL and CD4(+) Th1 responses to the TAA survivin. The DAI-enhanced CTL induction required nuclear factor κB (NF-κB) activation and type I IFN signaling, but did not involve the IFN regulatory factor 3 (IRF3). Codelivery of pDAI also increased CTL responses to the melanoma-associated antigen tyrosinase-related protein-2 (TRP2), enhanced tumor rejection and conferred long-term protection against B16 melanoma challenge. This study constitutes "proof-of-principle" validating the use of intracellular PRRs as genetic adjuvants to enhance DNA vaccine potency.
Aluminum localization in bone from hemodialyzed patients: Relationship to matrix mineralization
Authors: Giulia Cournot-Witmer, Johanna Zingraff, Jean Jacques Plachot, Françoise Escaig, Roger Lefèvre, Pierre Boumati, Agnès Bourdeau, Michèle Garabédian, Pierre Galle, Raymond Bourdon, Tilman Drüeke, Sonia Balsan
Journal: Kidney International (1981)
Detection of Early Sympathetic Cardiovascular Neuropathy by Squatting Test in NIDDM
Authors: Raffaele Marfella, Teresa Salvatore, Dario Glugliano, Giosue Di Maro, Riccardo Giunta, Roberto Torella, Jacques Juchmes, Andre Scheen, Pierre J Lefebvre
Journal: Diabetes Care (1994)

OBJECTIVE To determine the role of the squatting test in the detection of early sympathetic neuropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS Three groups of nonsmoking, nonobese subjects were studied: 10 healthy subjects, 10 NIDDM patients without autonomic neuropathy (AN), and 10 NIDDM patients with AN defined by the presence of a pathological deep-breathing value. All subjects were given three postural tests: lying-to-standing, sitting-to-standing, and squatting test. Heart rate (HR) and finger arterial pressure were recorded with a noninvasive technique. RESULTS Blood pressure (BP) fall (expressed as decremental area) was not significantly different among the groups at standing up after sitting or lying. By contrast, a significantly greater BP drop occurred in NIDDM patients with AN (1,123 ± 245 mm2) compared with NIDDM patients without AN (460 ± 232 mm2) or normal subjects (429 ± 138 mm2, P &amp;lt; 0.001). The HR increase after all the orthostatic maneuvers was smaller in diabetic patients with AN (P &amp;lt; 0.01) compared with that recorded in other groups. Significant correlations were observed between BP fall after squatting and either the expiration:inspiration ratio at deep breathing (r = -0.77, P &amp;lt; 0.001) or the duration of diabetes (r = 0.76, P &amp;lt; 0.001). CONCLUSIONS The intrinsic orthostatic load of the squatting test, which is greater than conventional postural maneuvers, makes the squatting test an easy and useful test to detect early orthostatic dysregulation in NIDDM.
α-Synuclein Expression in Rat Substantia Nigra Suppresses Phospholipase D2 Toxicity and Nigral Neurodegeneration
Authors: Oleg S Gorbatyuk, Shoudong Li, Frederic Nha Nguyen, Fredric P Manfredsson, Galina Kondrikova, Layla F Sullivan, Craig Meyers, Weijun Chen, Ronald J Mandel, Nicholas Muzyczka
Journal: Molecular Therapy (2010)

We present genetic evidence that an in vivo role of α-synuclein (α-syn) is to inhibit phospholipase D2 (PLD2), an enzyme that is believed to participate in vesicle trafficking, membrane signaling, and both endo- and exocytosis. Overexpression of PLD2 in rat substantia nigra pars compacta (SNc) caused severe neurodegeneration of dopamine (DA) neurons, loss of striatal DA, and an associated ipsilateral amphetamine-induced rotational asymmetry. Coexpression of human wild type α-syn suppressed PLD2 neurodegeneration, DA loss, and amphetamine-induced rotational asymmetry. However, an α-syn mutant defective for inhibition of PLD2 in vitro also failed to inhibit PLD toxicity in vivo. Further, reduction of PLD2 activity in SNc, either by siRNA knockdown of PLD2 or overexpression of α-syn, both produced an unusual contralateral amphetamine-induced rotational asymmetry, opposite to that seen with overexpression of PLD2, suggesting that PLD2 and α-syn were both involved in DA release or reuptake. Finally, α-syn coimmunoprecipitated with PLD2 from extracts prepared from striatal tissues. Taken together, our data demonstrate that α-syn is an inhibitor of PLD2 in vivo, and confirm earlier reports that α-syn inhibits PLD2 in vitro. Our data also demonstrate that it is possible to use viral-mediated gene transfer to study gene interactions in vivo.
Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis
Authors: R. Dahl, A. Stender, S. Rak
Journal: Allergy (2005)

The best way to prevent allergy symptoms is to treat the allergic condition. Specific immunotherapy with grass allergen tablets 75,000 SQ-T (Grazax, Phleum pratense, ALK-Abelló) is safe and efficacious in rhinoconjunctivitis patients. As rhinoconjunctivitis often co-exists with asthma, we aimed to confirm safety and efficacy in grass allergic subjects with asthma and rhinoconjunctivitis.A randomized, double-blind, placebo-controlled, multicentre trial was performed 10-14 weeks prior to and during the grass pollen season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets or placebo. The primary end points were average asthma medication and symptom scores during the grass pollen season, and secondary variables were average rhinoconjunctivitis symptom and medication scores during the grass pollen season. Additionally, number of well days was defined post hoc.Differences in asthma medication and symptom scores between the treatment groups were negligible. The mean difference in asthma medication score was below 0.1 and 0.3 for asthma symptom score [a single inhalation of salbutamol (200 microg) was scored 2]. No serious adverse events were reported. A reduction in rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036) reduction in medication score was found in the grass pollen season for subjects treated with the grass allergen tablet compared with placebo. Well days increased by 54% (P = 0.002).Self-administration of the grass allergen tablet was safe. The treatment did not impair asthma control and confirmed considerable symptom prevention and reduced medication use. It addresses the allergic condition and represents a baseline treatment for grass pollen allergy.
Prevention of Pulmonary Emboli With a Vena Caval Clip
Authors: Rodman E. Taber
Journal: JAMA (1966)

A serrated teflon clip for partially occluding the inferior vena cava to prevent pulmonary embolism has been used in the management of thromboembolic disease in 42 patients. Experimental testing of the device demonstrated that it trapped all emboli of 5 mm or larger diameter. Pulmonary angiography preoperatively was used in eight patients to confirm the clinical impression of embolism. Indications for the clip were formation of emboli in patients on anticoagulant therapy and others with contraindications to these drugs. There has been no operative mortality due to use of the clip nor postoperative pulmonary embolization following its application. Four patients who apparently had no further embolus formation after clipping were studied by postoperative venograms of the inferior vena cava and passage of a cardiac catheter through the clip site. The cava was patent in each.
Relationship between neurohumoral activation, severity of left ventricular dysfunction (LVD) and clinical status
Authors: Claude R Benedict, David E Johnstone, Martial G Bourassa, Vera Bittner, Glenda Blackburn, Barry Greenberg, Richard Kay, Philip Kirlin, Robert M Kohn, Kevin McIntyre, Melvin B Weiss, Debra Weiner, Salim Yusuf
Journal: Journal of the American College of Cardiology (1991)
Incidental Detection of Pigmented Villonodular Synovitis on FDG PET
Authors: Mehmet T. Kitapci, R. Edward Coleman
Journal: Clinical Nuclear Medicine (2003)

18 Fluorine fluorodeoxyglucose (FDG) has been used extensively in positron emission tomographic (PET) imaging for oncology. FDG is a glucose analog demonstrating enhanced uptake in the majority of malignant as well as granulomatous lesions. Although a few cases of pigmented villonodular synovitis using bone scanning agents Tl-201 chloride, Ga-67 citrate, and Tc-99m pentavalent dimercaptosuccinic acid have been published, to our knowledge FDG PET imaging of pigmented villonodular synovitis has not.
1003-2 Left and Right Atrial Systolic Function After the Maze Procedure: A Long-term Echo-Doppler Follow-up Study
Authors: Allan L. Klein, Abdulhay Albirini, Mario Garcia, R. Daniel Murray, Annitta Morehead, Brian L. Luvisi, Jill A. Odabashian, Mina K. Chung, Patrick M. McCarthy
Journal: Journal of the American College of Cardiology (1995)
Identification of the major Aβ1–42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition
Authors: Nobuhisa Iwata, Satoshi Tsubuki, Yoshie Takaki, Kaori Watanabe, Misaki Sekiguchi, Emi Hosoki, Maho Kawashima-Morishima, Hahn-Jun Lee, Emi Hama, Yoko Sekine-Aizawa, Takaomi C. Saido
Journal: Nature Medicine (2000)
Histoptysis or oncoptysis: suggested terms for tissue expectoration
Authors: A. Papagiannis, F. Macbeth
Journal: BMJ (2010)

Expectoration of abnormal tissue leading to pulmonary diagnosis is a rarely reported event.1 2 3 4 5 Spurred by personal experience of one such episode, we would like to propose a name for this strange clinical manifestation.

A 65 year old man underwent heart surgery in 2002. In the course of the procedure an incidentally …
New Strategies in Chronic Lymphocytic Leukemia: Shifting Treatment Paradigms
Authors: Farrukh T. Awan, John C. Byrd
Journal: Clinical Cancer Research (2014)

Over the past two decades, slow but deliberate progress has been made in understanding the genetics of chronic lymphocytic leukemia (CLL) and how the surrounding microenvironment influences leukemia cell survival. The complexity of CLL with respect to different chromosomal aberrations, lack of a common aberrant signaling pathway activation, and associated immune suppression of the disease has been seen a major stumbling block for developing a single targeted therapy similar to imatinib used in chronic myeloid leukemia. The upcoming therapeutic era we are entering with the B-cell receptor (BCR) tyrosine kinase inhibitors ibrutinib and idelalisib appears to be overcoming this obstacle. Indeed, for the large majority of patients, it appears that application of BCR kinase inhibitors can promote durable remissions without the need for chemotherapy. Where other very active targeted agents such as ABT-199, therapeutic antibodies, and chimeric antigen receptor-modified T-cells will be used in CLL also represents a major question that future clinical trials will answer.
Mutants, hyperlipoproteinaemia, and coronary artery disease.
Authors: D S Fredrickson
Journal: BMJ (1971)

s Regional Medical Program (Atherosclerosis Study Group, 1970).The Commis- sion was originally created to survey the nation's resources for treating circulatory diseases.Quite probably appalled by the rising demand for acute coronary care, it has instead dedicated this one of its several reports to suggestions for eliminating some of the need through preventive action.These are impeccable motives, and the goal will have unanimous support.All the interested parties, however, will not agree with all of the Commission's present recommendations.On the dietary side the Commission urges three precautions on all Americans from infancy to the grave.The first, to maintain optimal weight, will inspire no opposition, but perhaps will always fail to obtain maximal participation.The second, a requiem for the egg, is to eat less than 300 mg of cholesterol each day.The third is to consume what comes to about 30' of total calories from fat, to be equally divided between saturated, monounsaturated, and polyunsaturated sources.The last two strictures are sure to be controversial.The Commission offers some praiseworthy suggestions for implementing its advice.These include several directed at the cholesterol-raising elements in cows' milk, shortcomings that this animal doubtless would gladly overcome if she could, but which seem to be locked into the changeless biochemical programme of her rumen.The Commission advocates upsetting the general use of butter fat content to set the wholesale prices of dairy products, ending the prohibition against adding vegetable fats to meat products, a process now declared "adulteration," and revcrsing the regulations of some states and of certain federal
Needle-free anaesthesia prior to botulinum toxin type A injection treatment of palmar and plantar hyperhidrosis
Authors: A. Benohanian
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Botulinum toxin type A (BTX‐A) has emerged as a new technique to treat intractable cases of focal hyperhidrosis (HH).1 Injections on the palms and soles, although effective, are very painful and need some form of anaesthesia. Peripheral nerve blockade, the standard method of anaesthesia used, may have serious drawbacks,2 particularly when used repeatedly. Needle‐free anaesthesia may offer an alternative solution.3 The technique involves the use of needle‐free injection of 0·02–0·04 mL of 2% lidocaine without adrenaline prior to BTX‐A injection with needle. The mixture of lidocaine and BTX‐A does not jeopardize toxin potency.4 The device used to achieve needle‐free anaesthesia is the MED‐JET® MBX (Medical International Technologies, Montreal, QC, Canada; Fig. 1), which has the advantage over similar devices such as the Dermojet® (Robbins Instruments, Chatham, NJ, U.S.A.), of providing an adjustable range of volumes and pressures necessary to control the penetration depth. For palmar HH, the volume is adjusted to 0·02 mL per spurt (range 0·01–0·1 mL) and the pressure system set to 120 p.s.i. A first shot of lidocaine is discharged at the centre of the palm and if a superficial skin weal fails to appear, the pressure is steadily raised until a weal is obtained. Once the weal is formed, injections are evenly distributed at 1·5–2‐cm intervals over the whole palmar surface including the fingers. For plantar HH, higher volumes (0·04 mL) and pressure may be required to produce an anaesthetic weal. On average, 50 sites per hand or 30 sites per foot are injected in this manner. BTX‐A is injected through a 31 gauge needle preferably after each sequence of four or five lidocaine weals (Fig. 2). Injections are carried out intradermally rather than subcutaneously in an attempt to reduce the incidence of significant muscular weakness.5 Universal precautions including full‐face shield or face mask and protective eyeglasses are taken to avoid contamination caused by potential blood splatter. The device has recently been approved by Health Canada, and U.S. Food and Drug Administration approval is pending.
Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros
Authors: Hilde Schjerven, Jami McLaughlin, Teresita L Arenzana, Seth Frietze, Donghui Cheng, Sarah E Wadsworth, Gregory W Lawson, Steven J Bensinger, Peggy J Farnham, Owen N Witte, Stephen T Smale
Journal: Nature Immunology (2013)
Alfred Gordon Hooker
Authors: J. Hooker
Journal: BMJ (2002)

Former general practitioner Ludlow (b Foochow, China, 1916; q University College Hospital 1940), d 12 March 2002.

Gordon's early years were spent in China, where his father was a medical missionary. After house jobs at Hemel Hempstead he joined the Royal Army Medical Corps. Within a few weeks of landing in north Africa in November 1941 he was captured and spent 18 months each in Italy and Germany before he escaped via Russia. After the war he was a traditional family doctor in Ludlow for 35 years. Gordon had a great love of nature and enjoyed classical music. He leaves a wife of 60 years, Joan; two children; and four grandchildren.
Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin
Authors: Kai Kessenbrock, Leopold Fröhlich, Michael Sixt, Tim Lämmermann, Heiko Pfister, Andrew Bateman, Azzaq Belaaouaj, Johannes Ring, Markus Ollert, Reinhard Fässler, Dieter E. Jenne
Journal: Journal of Clinical Investigation (2008)

Neutrophil granulocytes form the body's first line of antibacterial defense, but they also contribute to tissue injury and noninfectious, chronic inflammation. Proteinase 3 (PR3) and neutrophil elastase (NE) are 2 abundant neutrophil serine proteases implicated in antimicrobial defense with overlapping and potentially redundant substrate specificity. Here, we unraveled a cooperative role for PR3 and NE in neutrophil activation and noninfectious inflammation in vivo, which we believe to be novel. Mice lacking both PR3 and NE demonstrated strongly diminished immune complex-mediated (IC-mediated) neutrophil infiltration in vivo as well as reduced activation of isolated neutrophils by ICs in vitro. In contrast, in mice lacking just NE, neutrophil recruitment to ICs was only marginally impaired. The defects in mice lacking both PR3 and NE were directly linked to the accumulation of antiinflammatory progranulin (PGRN). Both PR3 and NE cleaved PGRN in vitro and during neutrophil activation and inflammation in vivo. Local administration of recombinant PGRN potently inhibited neutrophilic inflammation in vivo, demonstrating that PGRN represents a crucial inflammation-suppressing mediator. We conclude that PR3 and NE enhance neutrophil-dependent inflammation by eliminating the local antiinflammatory activity of PGRN. Our results support the use of serine protease inhibitors as antiinflammatory agents.
Optimal Antiviral Prophylaxis Against Hepatitis B Reactivation in Patients Receiving Rituximab-Based Chemotherapy for Lymphoma
Authors: Jeremy S. Abramson, Raymond T. Chung
Journal: JAMA (2014)

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Survival Benefit of the Implantable Cardioverter-Defibrillator in Patients on the Waiting List for Cardiac Transplantation
Authors: Sigrid E. Sandner, Georg Wieselthaler, Andreas Zuckermann, Shahrokh Taghavi, Herwig Schmidinger, Richard Pacher, Meinhard Ploner, Guenther Laufer, Ernst Wolner, Michael Grimm
Journal: Circulation (2001)

The implantable cardioverter-defibrillator (ICD) effectively reduces sudden cardiac death in patients with severe LV dysfunction. Effect of ICD therapy on total mortality in patients on the waiting list for cardiac transplantation is still uncertain.We retrospectively analyzed 854 unselected consecutive patients (ICD therapy, n=102; 11.9%) on the waiting list for cardiac transplantation between January 1992 and March 2000. Actuarial 12-month total mortality rate on the waiting list was 24.2%; sudden cardiac death was the predominant mode of death (66.7% of total deaths). Kaplan-Meier analysis revealed improved survival for ICD (total mortality, 13.2%) compared with non-ICD (total mortality, 25.8%) patients (log rank, P=0.03). No event of sudden death occurred in ICD patients, whereas in non-ICD patients, 12-month sudden death rate was 20.1% (P=0.0001). Nonsudden death rates did not differ between ICD and non-ICD patients (P=0.16). A Cox proportional hazards model demonstrated that absence of an ICD was a powerful independent predictor of total mortality (P=0.02; relative risk, 2.22; 95% confidence interval, 1.16 to 4.17) and sudden cardiac death (P<0.0001; infinite relative risk) on the waiting list.ICD therapy, because it prevents sudden cardiac death, significantly improves survival on the waiting list for cardiac transplantation. The present study supports the use of ICDs as a bridge to transplantation in patients who are at risk of sudden cardiac death. Prospective randomized trials are needed to evaluate the potential benefit of prophylactic ICD therapy as a bridge to transplantation in all patients on cardiac transplant waiting lists.