tbuckley/cabot-search huggingface dataset:
Novel semliki forest virus vectors with reduced cytotoxicity and temperature sensitivity for long-term enhancement of transgene expression
Authors: Kenneth Lundstrom, Alessandra Abenavoli, Antonio Malgaroli, Markus U Ehrengruber
Journal: Molecular Therapy (2003)

Alphaviral vectors inhibit host cell protein synthesis and are cytotoxic. To overcome these limitations, we modified the nonstructural protein-2 (nsP2) gene in the Semliki Forest virus (SFV) vector, pSFV1. Packaging of SFV replicons with two point mutations in nsP2 resulted in high-titer recombinant SFV(PD) particles. SFV(PD) led to more efficient host cell protein synthesis, exhibited reduced cytotoxicity and improved cell survival, and allowed greater and prolonged transgene expression than the original vector, SFV. In dissociated hippocampal neurons and organotypic rat hippocampal slices, SFV(PD) infection preserved neuronal morphology and synaptic function more efficiently than SFV. Combination of the two point mutations with a replication-persistent mutation in nsP2 resulted in a highly temperature-sensitive vector, SFV(PD713P), which efficiently transduced neurons in hippocampal slice cultures. At 31 °C, SFV(PD713P) allowed continuous transgene expression in BHK cells, at amounts comparable to SFV(PD). These new SFV mutants are expected to substantially broaden the application of alphaviral vectors in neurons and other mammalian cells.
TRANSPLANTATION OF CARDIOGENIC CELLS DIFFERENTIATED FROM MESENCHYMAL STEM CELLS IMPROVES CARDIAC REPAIR IN ISCHEMIC HEARTS
Authors: Ki-Chul Hwang, Byeong-Wook Song, Heesang Song, Min-Ji Cha, Eunju Choi, Onju Ham, Namsik Chung, Yangsoo Jang
Journal: Journal of the American College of Cardiology (2010)
Attenuated Measles-Virus Vaccine
Authors: Albert Z. Kapikian
Journal: JAMA (1962)

Attenuated measles-virus vaccine and gamma globulin were administered to a group of children, while another group of randomly selected controls received only gamma globulin. Six of 8 nonimmune vaccinees, and 3 of 9 controls developed febrile episodes of 38.1° C. (100.6° F.) or greater from 4 to 14 days after inoculation. The febrile episodes experienced by the vaccinees were probably due both to vaccine reactions and to intercurrent infections, since the controls tended to develop fewer and milder febrile episodes. None of the vaccinees developed either Koplik spots or a rash. Thirteen of 14 nonimmune vaccinees developed measles hemagglutination inhibition antibody after vaccination. During an outbreak, all of 12 controls and only one of 10 vaccinees developed measles, indicating that the vaccination had rendered significant protection.
Nutrition for Sport
Authors: Ivan M. Sharman
Journal: British Journal of Sports Medicine (1988)

This is a reworked edition of Carl Honig's original text with many improvements particularly in terms of clarity.The themes of 'reserve of function' and the 'systems concept' run throughout the book which is divided into five parts.quote from the Preface which states that; 'The first two deal with the biophysical essentials: cardiac mechanics, electrophysiology, and hemodynamics.The third part is concerned with exchanges between blood and tissue, including new concepts in °2 transport.The fourth part describes selected regional circulations.This idiosyncratic material has been simplified by use of a common approach.The final part develops the regulation of pressure, flow, and volume and the integration of cardiovascular controls with voluntary behaviour."Each chapter contains clinical applications which highlight the relevance of the text and concludes with a brief but relevant list of references.The appendices include a number of problems and suggested approaches for solving them which is excellent revisionary material.The figures within the text utilise a full range of techniques including electron micrographs, flow diagrams and models.The book illustrates the importance of the basic physical sciences to full understanding.It will be a valued text for all medical or health science undergraduates and useful in many post-graduate courses.
On Sun-fever: Or Disturbance of the Cerebro-Spinal Functions by Excessive Heat
Authors: W. Strange
Journal: BMJ (1868)

TIEE distinguished author of the Address in 'Medicine recentlydelivered at Oxford, argues that recovery and subsequent immunity from such dis- eases as small-pox "are produced by a process of impregnation and assimilation, and not, as was early believed, and is still by some main- tained, of elimination."Dr. Gull goes on to say that " the old theory of depuration, though true of gross chemical poisons, as lead, or mer- ,cury, or arsenic, appears to have no application to those operation; which take place in the body in contagious diseases, as the effect of organic poisons."The question which is thus raised is one of consider p.bc scientific interest and practical importance.I have been at some
Reticuloendothelial function in renal allograft recipients.
Authors: G Drivas, P R Uldall, N Wardle
Journal: BMJ (1975)

The phagocytic capacity of the reticuloendothelial system (R.E.S.) was assessed in patients with chronic renal failure and in renal transplant recipients. R.E.S. phagocytosis was increased in the former group. Soon after transplantation R.E.S. phagocytosis was moderately reduced (through levels were comparable with those of normal controls) but was particularly reduced after high-dose corticosteroid treatment for rejection. In long-term allograft recipients R.E.S. phagocytosis was also depressed though steroid maintenance doses were small.
VARICELLA AND HERPES ZOSTER
Authors: Jacob Rosenberg
Journal: JAMA (1941)

To the Editor:—  In the discussion of the relationship of varicella to herpes zoster, so much importance has been in the past attached to the report of Cantor ( Brit. M. J.  2 :508, 1921) on the complete absence of varicella from a small island in the Straits Settlements on which zoster not uncommonly occurred that the following letter is of scientific as well as historical interest:  Christmas Island  Straits Settlements  April 3, 1941  Dear Dr. Rosenberg:  Replying to your letter of January 20, 1941, I am afraid Christmas Island lost its only claim to distinction in 1933 when 4 people, all old residents on the island, were diagnosed as suffering from varicella. Again in 1940 there was 1 case. With regards to herpes zoster, I can only find 1 case recorded. This occurred in 1936.  Trusting this information will be satisfactory,  Yours very truly,  J. Scott Clark, M.B., Ch.B.,  Medical
Normal Gallbladder Ejection Fraction After Morphine Augmentation
Authors: DWIGHT M. ACHONG, ELIZABETH OATES
Journal: Clinical Nuclear Medicine (1999)

Morphine sulfate causes spasm of the sphincter of Oddi. Conversely, the cholecystagogue sincalide produces relaxation of the sphincter and contraction of the gallbladder. This prospective study evaluated whether sincalide could produce normal gallbladder emptying after low-dose morphine sulfate (0.04 mg/kg).Thirty to 120 minutes (mean, 51 minutes) after morphine sulfate-augmented gallbladder visualization, 25 gallbladder ejection fractions in 24 patients were measured. One patient was studied twice, 2 weeks apart. Gallbladder ejection fractions were calculated after controlled 30-minute infusions of sincalide (0.02 microg/kg).Fourteen gallbladder ejection fractions were normal (mean, 63%; range, 45% to 80%) and 11 gallbladder ejection fractions were abnormal (mean, 12%; range, 5% to 19%; P < 0.001).Normal gallbladder ejection fractions can be obtained as early as 30 minutes after administration of low-dose morphine sulfate. Potential applications of post-morphine sulfate sincalide challenge would include, for example, to support true-negative morphine sulfate-augmented gallbladder visualization in a patient with a high clinically indicated potential of having acute cholecystitis.
Comparison between penicillamine and sulphasalazine in rheumatoid arthritis: Leeds-Birmingham trial.
Authors: V C Neumann, K A Grindulis, S Hubball, B McConkey, V Wright
Journal: BMJ (1983)

Sulphasalazine was first formulated by Svartz in the early 1940s, specifically for use as a remission inducing drug in rheumatoid arthritis. After the publication of an unfavourable trial, however, the drug was restricted to patients with ulcerative colitis. In the late 1970s sulphasalazine was re-examined in rheumatoid arthritis and favourable results reported in "open" trials. A double blind controlled trial was therefore conducted comparing enteric coated sulphasalazine and D-penicillamine in patients with active rheumatoid arthritis. A total of 63 patients were recruited in two centres; 31 were treated with sulphasalazine and 32 received penicillamine. After 16 weeks9 treatment both drugs had produced significant improvements in clinical score, pain score measured on a visual analogue scale, grip strength, Ritchie articular index, erythrocyte sedimentation rate, and serum C reactive protein concentration. Nausea was the major side effect in the sulphasalazine treated group. No potentially dangerous effects of sulphasalazine were encountered in contrast with those seen in the penicillamine group. The results suggest that sulphasalazine is an effective and safe drug capable of producing remissions in active rheumatoid arthritis. They also lend confidence to the use of preliminary "open" trials as a means of screening for remission inducing drugs in rheumatoid arthritis.
The small chill: mild hypothermia for cardioprotection?
Authors: R. Tissier, M. Chenoune, B. Ghaleh, M. V. Cohen, J. M. Downey, A. Berdeaux
Journal: Cardiovascular Research (2010)

Reducing the heart's temperature by 2-5°C is a potent cardioprotective treatment in animal models of coronary artery occlusion. The anti-infarct benefit depends upon the target temperature and the time at which cooling is instituted. Protection primarily results from cooling during the ischaemic period, whereas cooling during reperfusion or beyond offers little protection. In animal studies, protection is proportional to both the depth and duration of cooling. An optimal cooling protocol must appreciably shorten the normothermic ischaemic time to effectively salvage myocardium. Patients presenting with acute myocardial infarction could be candidates for mild hypothermia since the current door-to-balloon time is typically 90 min. But they would have to be cooled quickly shortly after their arrival. Several strategies have been proposed for ultra-fast cooling, but most like liquid ventilation and pericardial perfusion are too invasive. More feasible strategies might include cutaneous cooling, peritoneal lavage with cold solutions, and endovascular cooling with intravenous thermodes. This last option has been investigated clinically, but the results have been disappointing possibly because the devices lacked capacity to cool the patient quickly or cooling was not implemented soon enough. The mechanism of hypothermia's protection has been assumed to be energy conservation. However, whereas deep hypothermia clearly preserves ATP, mild hypothermia has only a modest effect on ATP depletion during ischaemia. Some evidence suggests that intracellular signalling pathways might be responsible for the protection. It is unknown how cooling could trigger these pathways, but, if true, then it might be possible to duplicate cooling's protection pharmacologically.
Delayed afterdepolarizations elicited in vivo by left stellate ganglion stimulation.
Authors: S G Priori, M Mantica, P J Schwartz
Journal: Circulation (1988)

Activation of cardiac sympathetic nerves is recognized as a triggering factor for cardiac arrhythmias. However, the mechanisms involved have only been speculated. Because evidence from studies in vitro has established a relation between catecholamines, delayed afterdepolarizations (DAD), and triggered rhythms, it seemed possible that in vivo adrenergic activation also might lead to the development of DAD. Because very little evidence was available for DAD in vivo, we have evaluated whether monophasic action potential (MAP) recording with a contact electrode could be a suitable technique for the detection of DAD from the endocardium of anesthetized cats. In six animals, atrial pacing and graded aortic constriction were performed during MAP recording to assess MAP stability during hemodynamic changes, and in no cases were modifications of the baseline observed. In 11 cats, calcium gluconate (0.5 g) and G-strophanthin (100 micrograms) were administered. Action potential duration at 50% (APD50) and 90% (APD90) repolarization were reduced (from 138 +/- 16 to 122 +/- 18 msec, p less than 0.02, and from 163 +/- 23 to 149 +/- 20 msec, p less than 0.025, respectively). In eight of 11 (73%) animals, DAD were elicited with a mean amplitude of 1.2 +/- 0.4 mV. In 14 cats, the left stellate ganglion was stimulated for 45 seconds. APD50 and APD90 decreased (from 153 +/- 15 to 145 +/- 16 msec, p less than 0.005, and from 176 +/- 18 to 165 +/- 13 msec, p less than 0.001, respectively). DAD were induced in 10 of 14 animals (71%) with a mean amplitude of 1.2 +/- 0.3 mV. These results show that DAD can be induced in vivo by administration of calcium and digitalis and by activation of the cardiac sympathetic nerves. This latter finding further strengthens the existing link between adrenergic activation and ventricular arrhythmogenesis and suggests triggered activity as a likely mechanism.
Abstract 2835: Combined stimulation of TLR9 and 4.1BB receptors enhances Trp2 peptide-mediated B16 melanoma regression by increasing Ag-specific CTL activity and infiltration to tumor sites.
Authors: Jeong-Im Sin, Hun Mo Ryoo
Journal: Cancer Research (2013)

Abstract We previously reported that intratumoral electroporation (IT-EP) with IL-12 cDNA (IT-EP/IL12) led to the eradication of established B16 melanoma tumors in mice. Tumor eradication required the participation of CD8+ T cells, but not CD4+ T cells and NK cells. IT-EP/IL12 induced antigen-specific CD8+ T cell responses against the immunodominant Trp2180-188 epitope and generated a systemic response, resulting in significant therapeutic effects against distal, untreated tumors. In this study, we observed that when Trp2180-188 self-peptides were combined with the TLR9 agonist, CpG-oligodeoxynucleotide (ODN) for antitumor immune therapy, self-tolerance was broken, giving rise to induction of Trp2-specific CTL responses and some antitumor activity against established melanoma (7 mm in mean diameter). A combination of anti-4.1BB antibodies with Trp2 peptides plus CpG-ODN increased the antitumor regression rate from 0 to 75%. This effect was concomitant with greater induction of Ag-specific CD8+ CTLs and their infiltration into the tumor sites, highlighting the importance of combined stimulation of TLR9 and 4.1BB for achieving tumor eradication. These findings may have implications for designing peptide-based therapeutic vaccines for cancer-patients. Citation Format: Jeong-Im Sin, Hun Mo Ryoo. Combined stimulation of TLR9 and 4.1BB receptors enhances Trp2 peptide-mediated B16 melanoma regression by increasing Ag-specific CTL activity and infiltration to tumor sites. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2835. doi:10.1158/1538-7445.AM2013-2835
Genetic modulation of soluble Aβ rescues cognitive and synaptic impairment in a mouse model of AD
Authors: Stephanie Fowler, Angie Chiang, Ricky Savjani, Megan Larson, Dorothy Schuler, John Cirrito, Sylvain Lesne, Joanna Jankowsky
Journal: Molecular Neurodegeneration (2013)

Background There has been a longstanding debate on whether amyloid plaques are pathogenic by causing physical damage to surrounding tissue or protective by sequestering more toxic soluble forms of amyloid b (Ab) peptide. Numerous studies in mouse models have documented a complex relationship between soluble Ab, deposited aggregates, and cognitive decline, but few experimental systems have been capable of dissecting how each form of the peptide contributes to the progressive memory deficits of Alzheimer’s disease. Here we use a controllable transgenic model expressing a mutant form of amyloid precursor protein (APP) to distinguish the impact of APP and soluble Ab from that of deposited amyloid on cognitive function and synaptic structure.
Renal biopsy findings among Indigenous Australians: a nationwide review
Authors: Wendy E. Hoy, Terence Samuel, Susan A. Mott, Priscilla S. Kincaid-Smith, Agnes B. Fogo, John P. Dowling, Michael D. Hughson, Rajalingam Sinniah, David J. Pugsley, Meshach G. Kirubakaran, Rebecca N. Douglas-Denton, John F. Bertram
Journal: Kidney International (2012)
Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma
Authors: D.S. Green, M.D. Bodman-Smith, A.G. Dalgleish, M.D. Fischer
Journal: British Journal of Dermatology (2006)

Background Patients with metastatic skin disease in malignant melanoma can be difficult to treat effectively, often requiring repeated treatments with different modalities in an attempt to control their disease. Treatment of nonsurgically resectable melanoma deposits is unsatisfactory, as they are often multiple and recurring. Anecdotal evidence from individual use of imiquimod in superficial metastases and intralesional interleukin (IL)-2 in subcutaneous deposits suggests that the combination may be more effective in bulky subcutaneous disease. Objectives To investigate the combination of topical imiquimod and, for selected lesions, intralesional IL-2, to treat a small cohort of patients with accessible melanoma metastases resistant to other treatments. Methods Thirteen patients were recruited: all had evidence of multiple cutaneous and/or subcutaneous metastases. Imiquimod was applied to the metastases on a daily basis for 4 weeks, before the introduction of intralesional IL-2. This was injected up to three times a week, into selected lesions, with 0·1 mL injected per lesion at a concentration of 3·6 MIU mL−1, a total of 1 mL being given at each session. The treated lesions were assessed individually at intervals of 3 months. Results Thirteen patients were treated, with 10 being eligible for assessment. In total, 182 lesions were treated: 137 purely cutaneous lesions and 41 subcutaneous lesions. Overall, a clinical response was seen in 92 lesions (50·5%) with 74 (40·7%) of these being a complete response (CR) with 91% of the CRs being in the cutaneous lesions. New lesions did appear during the treatment course; however, patients with cutaneous disease experienced a marked slowing of the appearance of new cutaneous lesions. No cutaneous lesions that responded reappeared on cessation of treatment. Conclusions The combination of imiquimod and IL-2 is effective in controlling this mixed cutaneous and subcutaneous disease, and is well tolerated. Imiquimod alone is often enough to elicit a response in purely cutaneous lesions. The addition of intralesional IL-2 increases the response rates in subcutaneous lesions, and in otherwise refractory cutaneous lesions.
Case of a Rare Form of Pulmonary Haemorrhage: With Brief Remarks
Authors: J. B. Bradbury
Journal: BMJ (1871)

CASE XLIV.-LouisDeroy was wounded on September Ist by a ball in the right elbow-joint.An operation had been performed in a Prussian field ambulance, on September 3rd, for removal of the injured joint by means of a single transvere incision across the back of the articulation.The patient was admitted to Asfeld on September 5th.The case did not get on well; and, on September 20th, the arm was amputated most skilfully by Dr. Wyman, and the patient eventually recovered, leaving Hospital on
NASAL AND EYE CHAMBERS FOR THE APPLICATION OF HEAT OR COLD
Authors: Jay N. Fishbein
Journal: JAMA (1928)

The nasal chamber was devised for use in nasal conditions requiring external applications of heat or cold. This chamber is made of light copper, shaped to the contour of the nose. It has an inlet and an outlet at the lowest and highest portions of the chamber, to which are connected rubber tubes. About the center of the lower tube is a bulb which, when compressed, creates a vacuum and in this manner fills the chamber. A valve in the bulb prevents its flowing back in the wrong direction. The lower ends of both tubes are weighed down by concealed weights to hold them in the basin. The chamber is kept in position on the nose by an adjustible elastic band around the head, beneath the occiput. The nasal chamber is useful following intranasal operations, such as submucous resections, turbinectomies and ethmoidectomies. Also, in cases in which ice compresses are indicated, as
The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia
Authors: Richard P. Allen, Sarah Auerbach, Huzefa Bahrain, Michael Auerbach, Christopher J. Earley
Journal: American Journal of Hematology (2013)

Restless Legs Syndrome (RLS) a common, under-recognized disorder disrupts sleep and diminishes quality of life. Despite a clear relation between low peripheral iron and increased prevalence and severity of RLS, the prevalence and clinical significance of RLS in iron-deficient anemic (IDA) populations is unknown. In this study all new patients referred for anemia to a community-based hematology practice over a 1-year period (March 2011-2012) were included if they had IDA and no RLS treatment. Patients completed a validated questionnaire identifying RLS, blood tests, and a sleep-vitality questionnaire (SVQ). Patients with RLS were compared to patients with no RLS for differences on SVQ, blood tests, baseline characteristics, and sleep quality. Three hundred forty-three patients were evaluated and 251 (89.2% female, average age of 45.6 years) included in the study. The prevalence of clinically significant RLS (RLS sufferers) was 23.9%, nine times higher than the general population. IDA-RLS sufferers reported poorer quality of sleep, decreased sleep time, increased tiredness, and decreased energy during the day compared to patients with IDA without RLS. Blood tests did not relate to RLS diagnosis but RLS was less likely for African-American than Caucasian patients. Clinically significant RLS occurs commonly with IDA producing much greater disruption of sleep and shorter sleep times than does IDA alone. This indicates the need for identification of RLS with IDA and consideration of appropriate therapeutic interventions for this sizeable subgroup: either aggressive iron treatment to reduce the RLS symptoms or medications for RLS or both.
CD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection
Authors: Brian J. Laidlaw, Nianzhi Zhang, Heather D. Marshall, Mathew M. Staron, Tianxia Guan, Yinghong Hu, Linda S. Cauley, Joe Craft, Susan M. Kaech
Journal: Immunity (2014)
Dr Arthur W. Swann
Authors: Mark S. Bernhardt
Journal: JAMA Dermatology (2013)

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