tbuckley/cabot-search huggingface dataset:
Specific Targeting of Brain Tumors with an Optical/Magnetic Resonance Imaging Nanoprobe across the Blood-Brain Barrier
Authors: Omid Veiseh, Conroy Sun, Chen Fang, Narayan Bhattarai, Jonathan Gunn, Forrest Kievit, Kim Du, Barbara Pullar, Donghoon Lee, Richard G. Ellenbogen, Jim Olson, Miqin Zhang
Journal: Cancer Research (2009)

Abstract Nanoparticle-based platforms have drawn considerable attention for their potential effect on oncology and other biomedical fields. However, their in vivo application is challenged by insufficient accumulation and retention within tumors due to limited specificity to the target, and an inability to traverse biological barriers. Here, we present a nanoprobe that shows an ability to cross the blood-brain barrier and specifically target brain tumors in a genetically engineered mouse model, as established through in vivo magnetic resonance and biophotonic imaging, and histologic and biodistribution analyses. The nanoprobe is comprised of an iron oxide nanoparticle coated with biocompatible polyethylene glycol–grafted chitosan copolymer, to which a tumor-targeting agent, chlorotoxin, and a near-IR fluorophore are conjugated. The nanoprobe shows an innocuous toxicity profile and sustained retention in tumors. With the versatile affinity of the targeting ligand and the flexible conjugation chemistry for alternative diagnostic and therapeutic agents, this nanoparticle platform can be potentially used for the diagnosis and treatment of a variety of tumor types. [Cancer Res 2009;69(15):6200–7]
Defence Society Subscriptions
Authors: F. Pygott
Journal: BMJ (1972)

<h3>Objective</h3> To compare the risk of road traffic injury calculated using an exposure measure based on people’s mobility, person-hours travelled (person-hours), with the risk obtained using population census, vehicle fleet and vehicle-kilometres travelled. <h3>Methods</h3> The rate of road traffic injury on a working day in Catalonia in 2006 was calculated using the number of people injured from the Register of Accidents and Victims of the National Traffic Authority and as denominator: person-hours travelled, from the 2006 Daily Mobility Survey of Catalonia; population census and vehicle fleet, from the National Statistics Institute; and vehicle-kilometres, from the Ministry of Public Works. <h3>Results</h3> Compared with person-hours travelled: population census may underestimate the risk in groups with low mobility; vehicle-kilometres may underestimate the risk in regions with high level of non-motorised mobility and high use of public transport; vehicle fleet may underestimate the risk for collective forms of transport such as buses and for motorcyclists who make many trips but of short duration. <h3>Conclusions</h3> Measures of exposure involving people9s mobility should be used in the estimation of road traffic injury risk, instead of vehicle9s mobility, population census or vehicle fleet.
Hepatitis B virus X protein transactivates inducible nitric oxide synthase gene promoter through the proximal nuclear factor κB-binding site: Evidence that cytoplasmic location of X protein is essential for gene transactivation
Authors: Pedro Majano, Enrique Lara-Pezzi, Manuel López-Cabrera, Arantxa Apolinario, Ricardo Moreno-Otero, Carmelo García-Monzón
Journal: Hepatology (2001)

Nitric oxide appears to play a central role in the pathogenesis of many inflammatory disorders. We have previously shown that there is an enhanced intrahepatic expression of the inducible nitric oxide synthase (iNOS) gene during chronic hepatitis B virus infection, and that viral X protein (HBx) transcriptionally activates this cellular gene, but the molecular basis for this activation remains to be defined. We aimed to explore the involvement of different cis-acting elements of the human iNOS promoter in the HBx-mediated up-regulation as well as the effect of the intracellular distribution of the HBx on its transacting function. Cotransfection of human hepatocyte-derived cells with wild-type or mutated iNOS promoter and with an HBx expression vector showed that functional inactivation of the proximal nuclear factor κB (NF-κB)-binding site of the iNOS promoter markedly reduced the HBx-mediated transcriptional activity. Mobility shift assays showed increased DNA-protein complexes comprising mainly the p50 and p65 members of NF-κB family in the nuclear extracts from HBx-transfected cells. Transient transfection experiments with HBx-expressing plasmids containing distinct cellular localization sequences showed that cytoplasmic location of this viral protein activated the iNOS promoter but when HBx was targeted to the nucleus, the HBx-induced luciferase activity was almost completely abrogated. In conclusion, cytoplasmic location of HBx protein is essential for the transcriptional activation of the iNOS gene through the nuclear translocation of p50-p65 heterodimers.
Impact of single centre status on estimates of intervention effects in trials with continuous outcomes: meta-epidemiological study
Authors: A. Bafeta, A. Dechartres, L. Trinquart, A. Yavchitz, I. Boutron, P. Ravaud
Journal: BMJ (2012)

<b>Objective</b> To compare estimates of intervention effects between single centre and multicentre randomised controlled trials with continuous outcomes. <b>Design</b> Meta-epidemiological study. <b>Data sources</b> 26 meta-analyses totalling 292 randomised controlled trials (177 single centre, 115 multicentre) with continuous outcomes published between January 2007 and January 2010 in the Cochrane database of systematic reviews. <b>Data extraction</b> Data were extracted on characteristics of trials, single or multicentre status, risk of bias using the risk of bias tool of the Cochrane Collaboration, and results. <b>Data synthesis</b> The intervention effects were estimated with standardised mean differences. For each meta-analysis, random effects meta-regression was used to estimate the difference in standardised mean differences between single centre and multicentre trials. Differences in standardised mean differences were then pooled across meta-analyses by a random-effects meta-analysis model. A combined difference in standardised mean differences of less than 0 indicated that single centre trials showed larger treatment effects, on average, than did multicentre trials. Because single centre trials may be more prone to publication bias and may have lower methodological quality than multicentre trials, sensitivity analyses were done with adjustment for sample size and domains of the risk of bias tool. <b>Results</b> Single centre trials showed larger intervention effects than did multicentre trials (combined difference in standardised mean differences −0.09, 95% confidence interval −0.17 to −0.01, P=0.04), with low heterogeneity across individual meta-analyses (I<sup>2</sup>=0%, between meta-analyses variance τ<sup>2</sup>=0.00). Adjustment for sample size slightly attenuated the difference (−0.08, −0.17 to 0.01). Adjustment for risk of bias yielded similar estimates with wider confidence intervals, some of them crossing 0 (−0.09, −0.17 to 0.00 for overall risk of bias). <b>Conclusions</b> On average, single centre clinical trials with continuous outcomes showed slightly larger intervention effects than did multicentre trials. Further research is needed to investigate potential causes of these differences.
Attenuation of diabetic nephropathy in diabetes rats induced by streptozotocin by regulating the endoplasmic reticulum stress inflammatory response
Authors: Wei Qi, Jiao Mu, Zhi-Feng Luo, Wei Zeng, Yan-Hong Guo, Qi Pang, Zi-Lin Ye, Li Liu, Fa-Huan Yuan, Bing Feng
Journal: Metabolism (2010)
Listen to the patient
Authors: J A Hicklin
Journal: BMJ (1992)

occurred more than seven weeks after his admission for self cutting.During five days of inpatient observation he was wary but coherent and rational.Repeated examination found no psychotic signs.With the ward team's agreement he was discharged into intensive community care, was seen repeatedly at his home and at the daily living programme team's base, managed well, and found a job.Two days after last being seen he suddenly killed a child and revealed previously concealed paranoid delusions.Had he remained an inpatient he could have absconded, avoided outpatient follow up, and become someone for whom district services could disclaim responsibility.Community care teams like the daily living programme team which do assertive outreach, however, continue their re- sponsibility for patients and thus their vulnerability to blame for adverse events.Conclusions from our study await our final report.They will have to balance the clinical and social outcomes, patients' and relatives' satisfaction, risk assessment, and an economic analysis.
ApoE controls the interface linking lipids and inflammation in atherosclerosis
Authors: Christian Weber, Oliver Soehnlein
Journal: Journal of Clinical Investigation (2011)

Atherosclerosis is a chronic inflammatory disease of the arterial walls that often leads to myocardial infarction and/or stroke. Hypercholesterolemia and an imbalance of peripheral leukocyte counts, leading to arterial leukocyte infiltration, are considered independent risk factors for atherosclerosis. However, in this issue of the JCI, Murphy and colleagues identify a mechanistic link between hypercholesterolemia, leukocytosis, and the subsequent development of atherosclerotic lesions in mice. These findings could pave the way for the development of novel treatment strategies to control leukocyte homeostasis and atherosclerosis.
Prevalence of Thrombus, Spontaneous Echo Contrast, and Atrial Stunning in Patients Undergoing Cardioversion of Atrial Flutter
Authors: Waleed N. Irani, Paul A. Grayburn, Imran Afridi
Journal: Circulation (1997)

Background Several studies have shown that patients undergoing cardioversion of atrial fibrillation have a high prevalence of of atrial thrombus and spontaneous echo contrast and frequently develop atrial stunning after restoration of sinus rhythm. These findings are strongly associated with increased risk of embolism in these patients. However, little is known about the prevalence of these markers of thromboembolism in patients undergoing cardioversion of atrial flutter. Methods and Results We performed transesophageal echocardiography in 47 consecutive, nonanticoagulated patients scheduled for elective cardioversion of atrial flutter. In patients who underwent successful cardioversion, mitral inflow velocity was recorded by transthoracic pulsed Doppler examination immediately after restoration of sinus rhythm. All patients were men (mean age, 65±10 years). Mean duration of flutter was 4±9 weeks. Atrial thrombus and/or spontaneous echo contrast were found in 16 patients (34%). Left atrial thrombus was seen in 5 patients (11%), either with (n=4) or without spontaneous contrast. Of 40 patients with successful cardioversion, atrial mechanical activity was absent in 28% immediately after restoration of sinus rhythm. Conclusions Our findings suggest that contrary to traditional teaching, atrial thrombus and spontaneous contrast are not uncommon in patients with atrial flutter and cardioversion may be associated with increased risk of thromboembolism.
Acute (LPS) and chronic airways inflammation blunts phagocytosis in vivo: Evidence of phenotype switching to a dendritic cell phenotype
Authors: N. Alexis
Journal: Journal of Allergy and Clinical Immunology (2005)

RATIONALE: We recently reported that phagocytosis of airway cells is blunted in healthy volunteers following LPS inhalation (5ug, ~30,000 EU), and that blunting is related to the magnitude of the neutrophil influx. We investigated whether phagocytosis is altered in disease states marked by "chronic" neutrophilic inflammation (COPD N=7, CF N=18) as compared to "acute" inflammation following LPS inhalation in normals (N=9), and if phagocytes undergo phenotype switching to a non-phagocytic dendritic cell (DC) phenotype. METHODS: Phagocytosis (IgG-opsonized zymosan particles) and DC surface phenotypes (HLA-DR, CD80, CD86) were analyzed on induced sputum and BALF (CF) cells by flow cytometry. RESULTS: Neutrophilia was present 6h following LPS challenge and in COPD and CF airways. Phagocytosis (Mac, Mono, PMNs) was significantly (p<0.05) blunted following LPS (20,000 EU) challenge (vs. pre-exposure) and constitutively decreased (p<0.05) in COPD (vs. healthy) and CF (vs. non-CF). HLA-DR and CD86 expression (MFI) were significantly elevated (p<0.05) on Mac and Mono following LPS, and the proportion of Mono co-expressing CD80/CD86 was significantly increased (p<0.05) following both LPS challenge and in COPD subjects. GM-CSF, a potent DC maturation agent, was significantly elevated (p<0.05) following LPS challenge. In vitro, sputum phagocytes incubated with supernatants from stimulated (PMA) blood PMNs showed decreased phagocytosis compared to un-stimulated supernatants. CONCLUSION: Both acute (LPS) and chronic (COPD, CF) airways inflammation blunt phagocytosis, and activated neutrophils likely contribute to this effect. Airway phagocytes appear to undergo phenotype switching to a less phagocytic, antigen presenting DC phenotype. This may enhance T-cell responses and ultimately sensitize the airway to subsequently inhaled allergic stimuli.
Genetic predictors for stroke in children with sickle cell anemia
Authors: Jonathan M. Flanagan, Denise M. Frohlich, Thad A. Howard, William H. Schultz, Catherine Driscoll, Ramamoorthy Nagasubramanian, Nicole A. Mortier, Amy C. Kimble, Banu Aygun, Robert J. Adams, Ronald W. Helms, Russell E. Ware
Journal: Blood (2011)
LOCAL SPECIFIC THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS
Authors: Fred W. Stewart
Journal: The Journal of Experimental Medicine (1927)

1. Fatal Type I pneumococcal meningitis may be produced in rabbits by intracisternal injection of pneumococci. 2. When organisms are of high virulence, the rabbit does not tend to localize them in the meninges, but an early septicemic process results. Death is septicemic rather than meningeal. 3. In such instances very little cellular reaction occurs in the meninges. 4. Active or passive immunization previous to intracisternal infection inhibits partially the septicemia and permits the development of reactional processes in the meninges. 5. The immunization likewise retards the meningeal disease, but multiplicity of factors prevents us from stating precisely to what this retardation is due. It is not correlated with the presence of agglutinins in the spinal fluid at the time of infection. 6. The rapidity of production of meningitis is influenced by the phase of growth of the culture used, and likewise by the growth activity of that culture. 7. To some extent in the partially immune rabbit the meningeal spaces constitute a relatively non-immune reservoir, constantly feeding the blood stream and breaking down systemic resistance. 8. Intrathecal serum treatment causes rapid agglutination and phagocytosis of pneumococci, and has very rarely, possibly, resulted in cure. Essentially no phagocytosis occurs in the absence of immune serum. 9. Phagocyted pneumococci stained supravitally take up the neutral red stain and are therefore probably injured. 10. The treatment employed subsequent to infection only slightly prolongs life in the majority of cases. It does retard septicemia. 11. The treatment improves the cellular reactional processes in the meninges. 12. A study of the pathology of rabbit pneumococcal meningitis shows that the location of pneumococci precludes complete contact with serum introduced intrathecally, and that these locations provide isolated foci, from which organisms may reinfect the meningeal spaces as rapidly as they are removed by lavage or antibody injections. 13. In recovered rabbits postmeningeal symptoms, weakness, ataxia, nystagmus, and paralyses arise. 14. In our opinion there is some objective evidence of benefit of serum therapy. The rabbit is too susceptible, however, and conditions too artificial to admit of definite conclusions. 15. Rough Type I pneumococci introduced in large quantity cisternally may kill and may be recovered 24 hours after infection, from spinal fluids. In a series of eleven passages, no reversion to smooth type occurred. In all animals injected with rough forms, transient bacteremia resulted.
IL-3, IL-5, granulocyte-macrophage colony- stimulating factor receptor α-subunit, and common β-subunit expression by peripheral leukocytes and blood dendritic cells☆☆☆★★★
Authors: Takashi Yamada, Qiyu Sun, Kyriaki Zeibecoglou, Jatinder Bungre, Janet North, A.Barry Kay, Angel F. Lopez, Douglas S. Robinson
Journal: Journal of Allergy and Clinical Immunology (1998)
Conservative Treatment of Fractures of the Shaft of the Tibia
Authors: James T. Tucker
Journal: JAMA (1961)

The authors review 115 fractures of the shaft of the tibia of which 111 were treated by closed conservative measures. Emphasis is placed on the use of the traction hitch for the closed reduction of such fractures. The end-results of all cases were studied to determine the period of healing from immobilization to full weight bearing. The average period was 26 weeks for all cases, with an average of 22 weeks for the closed fractures and 29 weeks for the open fractures. The complications encountered are reviewed. The method of treatment described is not new, but an appeal is made for a reevaluation, by all physicians treating tibial shaft fractures, of the inherent value of conservative means of treating such fractures.
Physician Travelers in Japan
Authors: Ilza Veith
Journal: JAMA (1965)

While Japan was pursuing its national policy of seclusion from the outside world (1640-1854), many European physicians nevertheless were able to visit that country. The Dutch East India Co., which alone enjoyed trading rights with Japan, employed physicians who brought European medicine to the Far East. In turn, they acquainted Europe with the totally strange world of Japan. Indeed, during the entire period of Japanese isolation they were the only ones who carried home any information from this distant and forbidden part of the world. In Japan they are remembered as excellent physicians and medical teachers; in the Western world, however, they are known for their superb detailed reports of Japan, its customs, its flora and fauna, and its medicine.  Engelbert Kaempfer  In Japan the changes and innovations introduced by European medicine were so gradual that they never entirely displaced the ancient belief in traditional medicine, particularly the belief in
THE ENHANCING EFFECT OF MURINE HEPATITIS VIRUS ON THE CEREBRAL ACTIVITY OF PLEUROPNEUMONIA-LIKE ORGANISMS IN MICE
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1957)

Pleuropneumoma-like organisms (PPLO) of the catarrhal type were isolated from the brain of a Swiss mouse during the cranial passage of mouse hepatitis virus-MHV(C). Cranial injection of the PPLO alone in Swiss and Princeton weanlings was attended by a meagre growth of the organisms in the brain, with no pathologic change. The growth of both catarrhal and conjunctival strains of PPLO in the brains of Swiss mice was greatly enhanced by the simultaneous injection of MHV(C). Rolling was not a characteristic sign prior to autopsy. Brain sections regularly showed a vigorous leukocytic response, commonly accompanied by the destruction of nerve cells in the anterior horns of the cerebrum. Injected in Princeton mice together with the virus, the organisms barely survived and were inactive. MHV(Pr) enhanced the growth and pathogenicity of PPLO in the brains of Princeton mice but failed to do so in Swiss. The behavior of PPLO in the brain was likewise affected by the presence of agar, as earlier observed by Findlay et al. In comparison with the effect of MHV, the enhancement was reduced in rate in both strains of mice and was not accompanied by outward signs of nervous disorder. Hydrocephalus which often followed injection of the PPLO-agar mixture was also produced by agar-bouillon alone.
Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice
Authors: Maya Kansara, Michael Tsang, Laurent Kodjabachian, Natalie A. Sims, Melanie K. Trivett, Mathias Ehrich, Alexander Dobrovic, John Slavin, Peter F.M. Choong, Paul J. Simmons, Igor B. Dawid, David M. Thomas
Journal: Journal of Clinical Investigation (2009)

Wnt signaling increases bone mass by stimulating osteoblast lineage commitment and expansion and forms the basis for novel anabolic therapeutic strategies being developed for osteoporosis. These strategies include derepression of Wnt signaling by targeting secreted Wnt pathway antagonists, such as sclerostin. However, such therapies are associated with safety concerns regarding an increased risk of osteosarcoma, the most common primary malignancy of bone. Here, we analyzed 5 human osteosarcoma cell lines in a high-throughput screen for epigenetically silenced tumor suppressor genes and identified Wnt inhibitory factor 1 (WIF1), which encodes an endogenous secreted Wnt pathway antagonist, as a candidate tumor suppressor gene. In vitro, WIF1 suppressed beta-catenin levels in human osteosarcoma cell lines, induced differentiation of human and mouse primary osteoblasts, and suppressed the growth of mouse and human osteosarcoma cell lines. Wif1 was highly expressed in the developing and mature mouse skeleton, and, although it was dispensable for normal development, targeted deletion of mouse Wif1 accelerated development of radiation-induced osteosarcomas in vivo. In primary human osteosarcomas, silencing of WIF1 by promoter hypermethylation was associated with loss of differentiation, increased beta-catenin levels, and increased proliferation. These data lead us to suggest that derepression of Wnt signaling by targeting secreted Wnt antagonists in osteoblasts may increase susceptibility to osteosarcoma.
Palliation of malignant dysphagia by ethanol induced tumour necrosis.
Authors: C U Nwokolo, J J Payne-James, D B Silk, J J Misiewicz, D E Loft
Journal: Gut (1994)

Thirty two patients (74 (43-93) years; median, (range)) with dysphagia because of inoperable, unresectable or recurrent oesophagogastric carcinoma were treated by ethanol induced tumour necrosis (ETN). Endoscopic injection of absolute alcohol was performed using a variceal injector needle, with 0.5-1 ml aliquots injected retrogradely from distal to proximal tumour margin. Dilatation to 12 mm was used only if the endoscope would not traverse the stricture. In patients with total occlusion, injection into the proximal tumour was followed by a repeat endoscopy 3-7 days later. Dysphagia was graded from 0 = no dysphagia to 4 = total dysphagia. The significance of changes in the dysphagia grade after ETN were assessed using the Wilcoxon rank sum test. Results (median (range)) were as follows: stricture length = 5.0 cm (1-15). Dysphagia grade before treatment was 3 (2-4) improving after first treatment to 1 (0-3), p < 0.003. Best dysphagia grade achieved was 1 (0-3) and interval between treatments was 28.5 days (4-170). The volume of ethanol injected = 10 ml (1.5-29) and survival after first treatment was 93 days (6-660). The number of treatment sessions required to achieve best grade = 1 (1-3). There were no treatment complications. ETN significantly improves dysphagia. Results of palliation are similar to those of laser therapy, but can be achieved quickly and safely on a day case basis in most patients and at a small proportion of the cost.
“Breast Is Best”: Modern Meanings
Authors: Derrick B. Jelliffe, E. F. Patrice Jelliffe
Journal: New England Journal of Medicine (1977)

Things are seldom what they seem, Skim milk masquerades as cream. — W.S. Gilbert (1878): H.M.S. Pinafore.For decades, the slogan "Breast Is Best" has been in use as a pious medical incantation. It has been based on unassailable support for motherhood, and on the ritual regurgitation of a list of textbook advantages and out-of-date comparisons of the major constituents of human and cow's milk, memorized in medical school.Translated into actual behavior by health staff, the result became a cliché with self-defeating overtones: "Breast feeding is best, but not really of actual importance." It was therefore foolish to bother . . .