tbuckley/cabot-search huggingface dataset:
Abstract 4883: Peptide-based PET imaging agents using novel bifunctional chelates and 64Cu
Authors: Rajanvir K. Gill, May Wong, Brent Sutherland, Sylvia Ng, Corrine Bensimon, Paul Jurek, Garry Kiefer, Donald T.T. Yapp, Cara Ferreira
Journal: Cancer Research (2011)

Abstract Introduction: Developing peptide-based PET imaging agents would be highly advantageous due to their high affinity and specificity. Two novel bifunctional chelates (BFC), PCTA and Oxo-DO3A, have previously been used to label antibodies with 64Cu. Complexation of 64Cu with PCTA and Oxo-DO3A was more efficient than with DOTA; the PCTA and OXO-DO3A complexes were also more stable and had more favourable pharmacokinetics[1]. Similarly, PCTA was also found to complex 68Ga more efficiently than DOTA[2]. The utility of PCTA and Oxo-DO3A for radiolabeling peptides specific for tumour angiogenesis processes were further investigated. Methods: The receptor number and affinity of RGD peptides were determined in mouse vascular endothelial cells. Mouse vascular endothelial cells were grown and varying amounts of I-125 echistatin were added to 1 million cells until receptors were saturated. A competitive binding assay, where a set amount of I-125 echistatin was added to the cells in the presence of unlabeled peptides, confirmed the specificity of the peptides for the target. In vivo studies were carried out in HT29 human colorectal tumors grown subcutaneously in RAG2M mice. 64Cu radiolabeled bioconjugates of PCTA, Oxo-DO3A and DOTA were injected with and without excess cyclo-(RGDyK) peptide. The amount of activity in the blood, tumor, liver, kidney and muscle was measured and compared to each of the BFC. Results: The binding assay revealed the saturation of mouse vascular endothelial cells was achieved when 0.8µci of I-125 echistatin was added. The competitive binding assay indicated an IC50 at a concentration of 9pM of DOTA-RGD. In vivo biodistribution studies showed good tumor to blood ratios for all of the 64Cu radiolabeled bioconjugates and better tumor to muscle ratios for the 64Cu radiolabeled bioconjugates of PCTA and Oxo-DO3A. Conclusion: The bifunctional chelates PCTA and Oxo-DO3A were found to be effective for radiolabeling peptides with 64Cu; the resulting complexes appear to be more stable than those of DOTA. The data show that PCTA and Oxo-DO3A radiolabel peptides more efficiently than DOTA, and that the resulting complexes are more stable. Angiogenesis in HT-29 tumours was also imaged successfully using the peptides labeled with PCTA and Oxo-DO3A. References: 1. C.L. Ferreira, D.T.T. Yapp. E. Lamsa, M. Gleave, C. Bensimon, P. Jurek, G.E. Kiefer, Nucl. Med. Biol. 35: 875-882 (2008) 2. C.L. Ferreira, E. Lamsa, M. Woods, Y. Duan, P. Fernando, C. Bensimon, M. Kordos, K. Guenther, P. Jurek, G.E. Kiefer, Bioconj. Chem. 21: 531-536 (2010) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4883. doi:10.1158/1538-7445.AM2011-4883
Abstract 2301: Cross-species expression profiling identifies novel genes differentially modulating epithelial-mesenchymal transition program and cell migration/invasion capability
Authors: Haijun Zhang, Sherwin Wu, Feng Wu, Stephen P. Ethier, Fred Miller, Guojun Wu
Journal: Cancer Research (2010)

Abstract Despite remarkable advances in research and clinical management, metastatic breast cancer remains incurable and causes most deaths in human breast cancer patients due to the unavailability of specific, targeted therapy. Therefore, identification of functional metastasis genes and further unveiling the molecular mechanisms underlying metastasis process remains the top priority in cancer research field. In recent years, much evidence supports the notion that epithelial-mesenchymal transition (EMT), a developmental program involved in a variety of tissue remodeling events, contributes to cancer cell plasticity and to the invasive potential of transformed epithelial cells. However, the legitimacy of EMT is still challenged by disagreements among pathologists who dismiss EMT as a fallacy. Utilizing a cross-species expression profiling strategy which combined microarray technique and model cell lines, we identified 22 up-regulated and 12 down-regulated genes as an essential genetic program in both human and mouse highly-metastatic model cell lines. About half of the gene candidates are novel and their roles in metastasis have not been reported. We randomly selected four genes and investigated their roles in metastatic characteristics including EMT program and cell migration and invasion. Overexpression of GCNT2 gene (an up-regulated gene candidate) not only led to a marked increase of cell migration and invasion, but also led to marked alterations in epithelial-mesenchymal transition (EMT) program. Ectopic expression of MAPK12 (another upregulated gene) only changed the EMT program but has no effect on cell migration and invasion. Overexpression of IRX5 (a down-regulated gene) not only led to a marked decrease of cell migration and invasion in vitro, but also a modulation of EMT program. However, expression of PHLDA3 (another down-regulated gene) only affect the cell migration and invasion, but has no effect on EMT program. These results highlight the feasibility of the cross-species expression profiling approach as a strategy to identify gene targets that are involved in breast cancer metastasis. The results of the functional studies for randomly selected genes further suggest that this multigenic program is consisted of different genes that play various roles in controlling EMT and/or Cell migration and invasion ability. Further studies are needed to investigate the effect of these novel gene candidates on metastasis in vivo and as therapeutic targets for treatment of breast cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2301.
Staphylococcus Infection Not Tuberculosis.
Authors: J. H. Voje
Journal: JAMA (1898)

Oconomowoc, Wis., Feb. 28, 1898. <h3>To the Editor:</h3> —Miss B. applied for treatment at Sanatorium Waldheim, Nov. 21, 1897, on account of a hacking cough, bloody expectoration, general emaciation and night sweats. The patient is single, a servant, 21 years of age. Both parents are dead; father died of tuberculosis; cause of mother's death unknown. Patient says she has always been well up to May, 1897, when she took a severe cold, causing a cough which lasted through the summer and increased toward autumn. She weighs 104 pounds, is anemic, cheeks slightly flushed and gives the impression of one in the second stage of tuberculosis. She coughs mostly toward night, expectorates (with difficulty) a small amount of blood-stained sputum and often vomits after a severe attack of coughing. She has anorexia, night sweats, and does not sleep well. Expansion of chest is fair, with slight dulness over both apices, harsh
Roles of dendritic cells in murine hepatic warm and liver transplantation-induced cold ischemia/reperfusion injury
Authors: Matthew Zhang, Shinya Ueki, Shoko Kimura, Osamu Yoshida, Antonino Castellaneta, Kikumi S. Ozaki, Anthony J. Demetris, Mark Ross, Yoram Vodovotz, Angus W. Thomson, Donna B. Stolz, David A. Geller, Noriko Murase
Journal: Hepatology (2012)

Abstract Dendritic cells (DCs) induce and regulate both innate and adaptive immune responses; however, their in vivo functional importance in hepatic ischemia/reperfusion (IR) injury is perplexing. We hypothesized that liver-resident DC and locally recruited blood-borne DC might have distinctive roles in hepatic IR injury. We tested this hypothesis by using DC-deficient, fms-like tyrosine kinase 3 ligand (Flt3L) knockout (KO) mice in hepatic warm (70% partial clamping for 60 minutes) and cold IR injury (liver transplant [LTx] with 24-hour cold storage). Flt3L KO liver and lymphoid organs contained virtually no CD11c+F4/80− DC. Hepatic warm IR injury was significantly lower in Flt3L KO than in wildtype (WT) mice with lower alanine aminotransferase (ALT) levels, reduced hepatic necrosis, and lower neutrophil infiltration. Hepatic messenger RNA (mRNA) and protein levels for inflammatory cytokines (tumor necrosis factor alpha [TNFα], interleukin [IL]-6) and chemokines (CCL2, CXCL2) were also significantly lower in Flt3L KO than in WT mice, indicating that lack of both liver-resident and blood-borne DC ameliorated hepatic warm IR injury. Adoptive transfer of splenic or hepatic WT DC into Flt3L KO or WT mice increased hepatic warm IR injury, suggesting injurious roles of DC infusion. When Flt3L KO liver was transplanted into WT mice, ALT levels were significantly higher than in WT to WT LTx, with enhanced hepatic necrosis and neutrophil infiltration, indicating a protective role of liver-resident DC. Conclusion: Using both warm and cold hepatic IR models, this study suggests differential roles of liver-resident versus blood-borne DC, and points to the importance of the local microenvironment in determining DC function during hepatic IR injury.
Personal paper: the scapegoating of a consultant orthopaedic surgeon
Authors: D. H Crawford
Journal: BMJ (1997)

At the end of last year Mr Anthony Percy accepted libel damages of £125 000 from the Mirror Newspaper Group in an out of court settlement.The Daily Mirror had called him Dr Dolittle-accusing him of failing to do everything he could to find a bed for a patient with a head injury.Dorothy H Crawford analyses how
Anti-HCV therapies in chimericscid-Alb/uPA mice parallel outcomes in human clinical application
Authors: Norman M. Kneteman, Amy J. Weiner, John O'Connell, Marc Collett, Tiejun Gao, Lea Aukerman, Rosemary Kovelsky, Zhi‐Jie Ni, Ahmad Hashash, Janine Kline, Belinda Hsi, Daniel Schiller, Donna Douglas, D Lorne J Tyrrell, David F. Mercer
Journal: Hepatology (2006)

Compounds with in vitro anti-hepatitis C virus (HCV) activity are often advanced directly into clinical trials with limited or no in vivo efficacy data. This limits prediction of clinical efficacy of compounds in the HCV drug pipeline, and may expose human subjects to unnecessary treatment effects. The scid-Alb-uPA mouse supports proliferation of transplanted human hepatocytes and subsequent HCV infection. Cohorts of genotype 1a HCV-infected mice were treated with interferon alpha-2b(IFN-alpha), BILN-2061 (anti-NS3 protease), or HCV371 (anti-NS5B polymerase). Mice treated with 1350 IU/g/day IFN-alpha intramuscularly for 10 to 28 days demonstrated reduced viral titers compared with controls in all five experiments (P < .05, t test); viral titers rebounded after treatment withdrawal. A more pronounced antiviral effect with IFN-alpha was seen in genotype 3a-infected mice. Pilot studies with BILN2061 confirmed exposure to 10X replicon EC50 at trough and reduced viral titer over 2 log at 4 days. In a second 7-day study, mean HCV RNA titers dropped 1.1 log in BILN2061-treated animals, 0.6 log in IFN-treated mice, and rose 0.2 log in controls (P = .013, ANOVA). Pre-existing mutants with partial resistance to BILN2061 were identified by sequencing both the human inoculum and sera from treated mice. The polymerase inhibitor HCV371 yielded a decline in HCV titers of 0.3 log relative to vehicle-treated controls (P = NS). Performance of all three antiviral regimens in the chimeric mouse model paralleled responses in humans. In conclusion, this system may help selection of lead compounds for advancement into human trials with an increased likelihood of clinical success while broadening the tools available for study of the biology of HCV infection.
Hepatocirculatory failure: Diverse pathogeneses deserve diverse therapies
Authors: Jay N. Cohn
Journal: Hepatology (1990)

In nine patients with decompensated alcoholic cirrhosis of the liver and impaired renal function the effect of 8–ornithin vasopressin (ornipressin) on renal function and haemodynamic parameters was studied. Ornipressin was infused at a dose of 6 IU/h over a period of four hours. During ornipressin infusion an improvement of renal function was achieved as indicated by an increase of creatinine clearance (76 (15)%; p &lt; 0.01), urine volume (108 (29)%; p &lt; 0.05) and sodium excretion (168 (30)% p &lt; 0.05). The hyperdynamic circulation of hepatic failure, as characterised by in creased systemic vascular resistance was reversed to a nearly normal circulatory state during ornipressin infusion. The raised noradrenaline plasma concentration (1.74 (0.31) ng/ml) and plasma renin activity (13.5 (3.9) ng/ml/h) were lowered during ornipressin infusion to 0.87 (0.21) ng/ml and 5.9 (2.1) ng/ml/h, respectively (p &lt; 0.01). The efficacy of a vasoconstrictor agent in reverting a hyperdynamic state and improving renal function provides evidence for the substantial role of accumulation of vasodilator substances and subsequent activation of sympathetic nervous system and reninangiotensin–axis in the pathogenesis of renal dysfunction in hepatic failure. Values are expressed as mean (SE).
Management of Massive Imipramine Overdosage with Mannitol and Artificial Dialysis
Authors: J. Warren Harthorne, Anthony M. Marcus, Michael Kaye
Journal: New England Journal of Medicine (1963)

IMIPRAMINE hydrochloride (Tofranil), the chemical analogue of promazine in the phenothiazine series, has the chemical formula of 5-(3-dimethyl-aminopropyl)-10,ll, dihydro-5H-dibenz (b, f) azepine hydrochloride and has been widely used1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 in the management of depression since its introduction in clinical trials by Kuhn3 in 1957. Side reactions include thirst, dryness of the mouth, hypotension, urinary retention, constipation and other anticholinergic effects.6 Cases of massive overdosage are recorded,8 9 10 11 12 13 14 15 and in doses over 1200 mg., certain common features are seen: deep coma; hypotension; myoclonic seizures; and defects in cardiac conduction.10 Previous papers8 , 9 , 12 have reported recovery after ingestion of as much as 1500 to 2500 . . .
Socioeconomic variation in incidence of epilepsy: prospective community based study in south east England
Authors: D. C Heaney
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To determine the incidence of epilepsy in a general practice population and its variation with socioeconomic deprivation. <b>Design:</b> Prospective surveillance for new cases over an 18 or 24 month period. <b>Participants:</b> All patients on practice registers categorised for deprivation with the Carstairs score of their postcode. <b>Setting:</b> 20 general practices in London and south east England. <b>Main outcome measure:</b> Confirmed diagnosis of epilepsy. <b>Results:</b> 190 new cases of epilepsy were identified during 369 283 person years of observation (crude incidence 51.5 (95% confidence interval 44.4 to 59.3) per 100 000 per year). The incidence was 190 (138 to 262) per 100 000 in children aged 0-4 years, 30.8 (21.3 to 44.6) in those aged 45-64 years, and 58.7 (42.5 to 81.0) in those aged 65 years. There was no apparent difference in incidence between males and females. The incidence showed a strong association with socioeconomic deprivation, the age and sex adjusted incidence in the most deprived fifth of the study population being 2.33 (1.46 to 3.72) times that in the least deprived fifth (P=0.001 for trend across fifths). Adjustment for area (London <i>v</i> outside London) weakened the association with deprivation (rate ratio 1.62 (0.91 to 2.88), P=0.12 for trend). <b>Conclusions:</b> The incidence of epilepsy seems to increase with socioeconomic deprivation, though the association may be confounded by other factors. <h3>What is already known on this topic</h3> Epilepsy is associated with a wide range of markers of social and economic disadvantage A small number of epidemiological studies have confirmed this association but have not established the direction of causality <h3>What this study adds</h3> The incidence of epilepsy, adjusted for age and sex, in the most deprived fifth of the study population was 2.3 times that in the least deprived fifth Socioeconomic deprivation is an important risk factor for the development of epilepsy, though the results may partly reflect differences in incidence within and outside London
CONTINUOUS ELASTIC TRACTION IN THE TREATMENT OF CERTAIN FRACTURES OF THE PHALANGES
Authors: Wesley Grove Vincent
Journal: JAMA (1918)

<h3>To the Editor:</h3> —The are occasional fractures of the phalanges in which it is difficult to hold the fragments in alinement by the methods usually employed. This applies especially to fractures of the phalanges of the toes, in which the fracture may be near the metatarsophalangeal junction and the toes are more or less deformed from the wearing of tight and narrow pointed shoes. Some time ago (The Journal, Jan. 12, 1918, p. 78) I called attention to a new method of correcting the deformity in greenstick fractures of the forearm through the use of continuous elastic traction; and recently I have employed this principle in caring for two cases of complete fracture of the phalanges of the toes, in which roentgenoscopy showed that the fragments were not held in proper alinement by ordinary methods of treatment and there would be considerable angular deformity. In one case the fracture was
Anthony J Hedley
Authors: J. Parry
Journal: BMJ (2015)

Public health researcher and advocate, with a focus on air pollution and tobacco control



Less than two weeks before his death, Anthony J Hedley made a trip back to Hong Kong, where he had lived and pursued an illustrious academic career in public health from 1988 until his retirement in 2010. The purpose of the trip was to attend a forum held by the University of Hong Kong’s School of Public Health—an event attended by more than 350 former colleagues, students, public health professionals, and friends—in honour of his contributions to public health both globally and within Hong Kong.

Hedley returned home to the Isle of Man with an emeritus professorship from the School of Public Health to add to the many other acknowledgements he had received. These included the honorary degree of MD, presented by Thailand’s King Bhumipol Adulyadej; a World Health Organization medal for outstanding contributions to public health; and, in 2000, the Hong Kong Special Administrative Region Bronze Bauhinia Star.

Hedley was a public health polymath—an old-school generalist who also became a deeply knowledgeable expert on a range of issues: air pollution, tobacco control, life course epidemiology, health services research, and the control of infectious disease. As well as producing a substantial body of research across these domains, he was also a passionate advocate. 

“He had a major role in ensuring that public health was recognised for its behavioural, economic, political, and advocacy dimensions,” said Richard Fielding, a former colleague and friend. “He …
1017. Selective Induction of Tumor-Associated Antigens in Murine Pulmonary Vasculature Using Double-Targeted Adenoviral Vectors
Authors: Maaike Everts, SangAe Kim-Park, Meredith A. Preuss, Michael J. Passineau, Joel N. Glasgow, Alexander V. Pereboev, Parameshwar J. Mahasreshti, William E. Grizzle, Paul N. Reynolds, David T. Curiel
Journal: Molecular Therapy (2005)

Targeted therapies directed to tumor-associated antigens are being investigated for the treatment of cancer. However, there are few suitable animal models for testing the ability to target these tumor markers. Therefore, we have exploited mice transgenic for the human coxsackie and adenovirus receptor (hCAR) to establish a new model for transient expression of human tumor-associated antigens in the pulmonary vasculature. Systemic administration of Ad in hCAR mice resulted in an increase in transgene expression in the lungs compared to wild type mice, as determined using a luciferase reporter gene. To reduce transgene expression in the liver, the predominant organ of ectopic Ad localization and transgene expression following systemic administration, we utilized the endothelial-specific flt-1 promoter, which resulted in a further increased lung-to-liver ratio of luciferase expression. Administration of an adenoviral vector encoding the tumor-associated antigen carcinoembryonic antigen (CEA) under transcriptional control of the flt-1 promoter resulted in selective expression of this antigen in the pulmonary vasculature of hCAR mice. Feasibility of targeting to expressed CEA was subsequently demonstrated using adenoviral vectors pre-incubated with a bifunctional adapter molecule recognizing this tumor-associated antigen, thus demonstrating utility of this transient transgenic animal model.
Effect of High-Dose Vitamin E on Insulin Resistance and Associated Parameters in Overweight Subjects
Authors: Patrick J. Manning, Wayne H.F. Sutherland, Robert J. Walker
Journal: Diabetes Care (2005)

We take issue with the points Vale (1) has raised. While it is established that vitamin E does not influence myeloperoxidase-catalyzed lipid peroxidation in vitro, this does not exclude possible benefits from vitamin E supplementation in vivo in subjects with increased myeloperoxidase activity and high risk of coronary heart disease. For example, supplementation with vitamin E reduced the risk of myocardial infarction, including sudden death in hemodialysis patients (2). Whether the antioxidant activity of vitamin E is responsible for this improved risk of coronary heart disease is unknown, and other effects of vitamin E may be implicated. As pointed out in our report, vitamin E …
Electrocardiographic Patterns in Man at High Altitudes
Authors: ANDRÉS ROTTA, ANDRÉS LÓPEZ
Journal: Circulation (1959)

Electrocardiograms of healthy men both native and long-term residents at 14,900 feet above sea level have been obtained and classified according to their dominant pattern. Most of the tracings showed signs of either right ventricular hypertrophy or right bundle-branch block, incomplete and complete. Some of the mechanisms responsible for these electrocardiographic changes found at high altitudes, such as pulmonary hypertension, positional changes of the heart, and chronic hypoxia, are discussed.
New techniques for imaging and analyzing lung tissue.
Authors: V L Roggli, P Ingram, R W Linton, W F Gutknecht, P Mastin, J D Shelburne
Journal: Environmental Health Perspectives (1984)

The recent technological revolution in the field of imaging techniques has provided pathologists and toxicologists with an expanding repertoire of analytical techniques for studying the interaction between the lung and the various exogenous materials to which it is exposed. Analytical problems requiring elemental sensitivity or specificity beyond the range of that offered by conventional scanning electron microscopy and energy dispersive X-ray analysis are particularly appropriate for the application of these newer techniques. Electron energy loss spectrometry, Auger electron spectroscopy, secondary ion mass spectrometry, and laser microprobe mass analysis each offer unique advantages in this regard, but also possess their own limitations and disadvantages. Diffraction techniques provide crystalline structural information available through no other means. Bulk chemical techniques provide useful cross-checks on the data obtained by microanalytical approaches. It is the purpose of this review to summarize the methodology of these techniques, acknowledge situations in which they have been used in addressing problems in pulmonary toxicology, and comment on the relative advantages and disadvantages of each approach. It is necessary for an investigator to weigh each of these factors when deciding which technique is best suited for any given analytical problem; often it is useful to employ a combination of two or more of the techniques discussed. It is anticipated that there will be increasing utilization of these technologies for problems in pulmonary toxicology in the decades to come.