tbuckley/cabot-search huggingface dataset:
221. Spermine-Grafted Hyaluronic Acid as Multifunctional Coating of the Plasmid/Polycation Complex for Protection, Targeting, and Transcriptional Activation
Authors: Tomoko Ito, Naoko Iida-Tanaka, Koji Kubo, Kenichi Yoshikawa, Yoshiyuki Koyama
Journal: Molecular Therapy (2005)

A variety of DNA/polycation complex have been explored as synthetic vectors. However, the surface of the DNA complex is usually positively charged, and undesirable interaction with blood components has been a problem especially for in vivo gene therapy. We reported that hyaluronic acid (HA) could coat the DNA/polycation complexes and effectively protect them from the non-specific interactions. Moreover, HA worked as a ligand for malignant cells expressing CD44, a receptor for HA.
Inability to detect failures at Mid Staffs means it could happen again, Francis concludes
Authors: N. Hawkes
Journal: BMJ (2013)

In his report into Mid Staffordshire NHS Foundation Trust Robert Francis avoids blaming individuals for what took place. But he also accepts the corollary of this judgment: if the failures were not a unique event caused by a few rogue staff, then it is difficult to have any confidence that it could not happen again.

Even if it were true that no other healthcare providers showed the same combination of deficiencies, he said, “it is of grave concern that the extensive system of checks and balances intended to detect such failures did not work.”1 Since the Healthcare Commission reported into Mid Staffs in March 2009, there had been, he said, a number of other critical reports of NHS services. Even if all the instances were in some way isolated ones that depended on particular circumstances, he said, “they are suggestive that there are other places where unhealthy cultures, poor leadership, and an acceptance of poor standards are too prevalent.”

The failure of the systems to detect deficiencies meant, he said, that the public was unlikely to have confidence that “another Stafford” did not exist. “Stafford was not an event of such rarity or improbability that it would be safe to assume that it has not been or …
Better theories are needed to distinguish perception from cognition
Authors: Michael R. W. Dawson, C. Darren Piercey
Journal: Behavioral and Brain Sciences (1999)

Pylyshyn argues that many of the methods used to study perception are too coarse to detect the distinction between perceptual and cognitive processing. We suggest that the reason for this is that the theories used to guide research in perception are at fault. More powerful theories – for instance, computer simulations – will be required to identify where perception ends and where cognition begins.
The role of superantigens in human diseases: therapeutic implications for the treatment of skin diseases
Authors: None Leung, None Hauk, None Strickland, None Travers, None Norris
Journal: British Journal of Dermatology (1998)

Although it is well established that immune mechanisms contribute to the pathogenesis of chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis, the actual events that trigger the immunological pathways resulting in these skin diseases are not well understood. Colonization and infection with Staphylococcus aureus and streptococci has been reported to exacerbate AD and psoriasis. Recent studies demonstrating that bacterial toxins can act as superantigens provide mechanism(s) by which S. aureus and streptococci could mediate an inflammatory skin lesion that consists predominantly of activated T‐cells and monocytes. This review will explore the diverse mechanisms by which bacterial superantigens can induce skin inflammation following systemic or local infection. These observations provide a new direction for the development of novel approaches for the treatment of skin inflammation.
The Risk of Suicide in Persons With AIDS
Authors: Mohan Beltangady
Journal: JAMA (1988)

To the Editor.—  Marzuk et al 1 present a detailed report of the first epidemiologic investigation of suicide in persons with acquired immunodeficiency syndrome (AIDS). While they use careful ascertainment methods and have done an excellent job in reporting the study, the relative risk is expressed as a ratio of the incidence densities (number of events per 100 000 person-years of follow-up) between the patients with AIDS and the general population. The result is a staggeringly high value of 36.30 among men 20 to 59 years of age.  While the relative - risk - estimate method is a common statistical tool in epidemiologic studies with long followup periods, its direct application without regard to the underlying assumptions is somewhat naive. The basic premise in using the ratio of incidence densities is that the potential personyears of follow-up in the two groups, if the events being studied did not occur , are comparable. The
INFLUENCE OF RAINY WINDS ON PHTHISIS
Authors: F. W. Pilkington
Journal: BMJ (1906)

Like leptin, the pancreatic hormone insulin is an important adiposity signal to the brain. We report that the hypothalamic melanocortin system is an important target of the actions of insulin to regulate food intake and body weight. Hypothalamic neurons expressing insulin receptors were found to coexpress the melanocortin precursor molecule pro-opiomelanocortin (POMC), and administration of insulin into the third cerebral ventricle of fasted rats increased expression of POMC mRNA. Finally, a subthreshold dose of the melanocortin antagonist SHU-9119 prevented the reduction in food intake caused by third-ventricular insulin administration. These data suggest that the hypothalamic melanocortin system mediates the anorexic effects of central insulin, as well as of leptin.
Genetic approaches to understanding human obesity
Authors: Shwetha Ramachandrappa, I. Sadaf Farooqi
Journal: Journal of Clinical Investigation (2011)

Obesity and its associated comorbidities represent one of the biggest public health challenges facing the world today. The heritability of body weight is high, and genetic variation plays a major role in determining the interindividual differences in susceptibility or resistance to the obesogenic environment. Here we discuss how genetic studies in humans have contributed to our understanding of the central pathways that govern energy homeostasis. We discuss how the arrival of technological advances such as next-generation sequencing will result in a major acceleration in the pace of gene discovery. The study of patients harboring these genetic variants has informed our understanding of the molecular and physiological pathways involved in energy homeostasis. We anticipate that future studies will provide the framework for the development of a more rational targeted approach to the prevention and treatment of genetically susceptible individuals.
The Amazing Noncollapsing U.S. Health Care System — Is Reform Finally at Hand?
Authors: Lawrence D. Brown
Journal: New England Journal of Medicine (2008)

For roughly 40 years, health care professionals, policymakers, politicians, and the public have concurred that the U.S. health care system is careening toward collapse. Lawrence Brown asks, if the consensus is so incontestable, why has the system not already collapsed?
Hypermethylation of the tumor suppressor gene PRDM1/Blimp-1 supports a pathogenetic role in EBV-positive Burkitt lymphoma
Authors: T Zhang, J Ma, K Nie, J Yan, Y Liu, C E Bacchi, E M Queiroga, G Gualco, J T Sample, A Orazi, D M Knowles, W Tam
Journal: Blood Cancer Journal (2014)

PRDM1/Blimp-1 is a tumor suppressor gene in the activated B-cell subtype of diffuse large B-cell lymphomas. Its inactivation contributes to pathogenesis in this setting by impairing terminal B-cell differentiation induced by constitutive nuclear factor-κB activation. The role of PRDM1 in Burkitt lymphoma (BL) lymphomagenesis is not known. Here we identified hypermethylation of the promoter region and exon 1 of PRDM1 in all six Epstein–Barr virus (EBV)-positive BL cell lines and 12 of 23 (52%) primary EBV-positive BL or BL-related cases examined, but in none of the EBV-negative BL cell lines or primary tumors that we assessed, implying a tumor suppressor role for PRDM1 specifically in EBV-associated BL. A direct induction of PRDM1 hypermethylation by EBV is unlikely, as PRDM1 hypermethylation was not observed in EBV-immortalized B lymphoblastoid cell lines. Treatment of EBV-positive BL cells with 5′ azacytidine resulted in PRDM1 induction associated with PRDM1 demethylation, consistent with transcriptional silencing of PRDM1 as a result of DNA methylation. Overexpression of PRDM1 in EBV-positive BL cell lines resulted in cell cycle arrest. Our results expand the spectrum of lymphoid malignancies in which PRDM1 may have a tumor suppressor role and identify an epigenetic event that likely contributes to the pathogenesis of BL.
Hemodynamic Effects of Pressor Agents in Septic and Myocardial Infarction Shock
Authors: Harold Smulyan, R. P. Cuddy, R. H. Eich
Journal: JAMA (1964)

Cardiac output (CO) was measured before and during pressor-amine infusion in eight patients with septic shock and in seven patients with shock from myocardial infarction. Levarterenol bitartrate or metaraminol bitartrate infusion in sufficient dosage to maintain systolic blood pressures of 90 to 130 mm Hg increased the peripheral resistance in both groups. These pressor amines tended to raise the CO in patients with sepsis and lower it in those with myocardial infarction. Increasing the pressor-amine dosage for greater bloodpressure effect consistently lowered the CO, which suggests that blood-pressure support at low normal levels is hemodynamically preferable. In three cases, angiotensen amide produced lower CO's than equipressor doses of levarterenol.
Human natural killer cells produce abundant macrophage inflammatory protein-1 alpha in response to monocyte-derived cytokines.
Authors: E M Bluman, K J Bartynski, B R Avalos, M A Caligiuri
Journal: Journal of Clinical Investigation (1996)

Once infected by obligate intracellular pathogens, monocytes/macrophages release cytokines that activate natural killer (NK) cells. NK cells in turn produce and secrete monocyte/macrophage activating factors such as interferongamma (IFN-gamma), which are important in the early control of these infections. Here we demonstrate that human NK cells are potent producers of another monocyte/macrophage-activating factor, macrophage inflammatory protein-1 alpha (MIP-1 alpha). Fresh NK cells produce negligible amounts of MIP-1 alpha after stimulation with the monocyte-derived cytokines IL-12, TNF-alpha, IL-1 beta, or IL-10, while stimulation with IL-15 alone results in modest MIP-1 alpha production. Abundant NK cell production MIP-1 alpha is seen after costimulation with IL-12 and IL-15, and is dose-dependent. Combinations of IL-12, with TNF-alpha, IL-1 beta, or IL-10 are substantially less effective inducers of MIP-1 alpha production by NK cells. NK cell MIP-1 alpha mRNA transcripts were detectable within 1 h after costimulation with IL-12 plus IL-15 and steadily increased over 24 h, with a concomitant increase in protein production detectable at 12 h. Resting NK cells constitutively express mRNA transcript for a MIP-1 alpha receptor, and costimulation with IL-12 and IL-15 upregulates its level of expression. Equilibrium binding studies with radioiodinated MIP-1 alpha were consistent with the induction of a single class of high affinity MIP-1 alpha receptors on NK cells costimulated with IL-12 and IL-15. Addition of exogenous MIP-1 alpha to resting NK cells did not enhance cytokine production, but did increase NK cytotoxic activity. The requirement for IL-15 as a critical cofactor for NK cell production MIP-1 alpha suggests a potentially unique role for this monocyte-derived cytokine in combination with IL-12. As MIP-1 alpha is known to potentiate the action of IFN-gamma on monocytes and to suppress human immunodeficiency virus replication, the NK cell's production of MIP-1 alpha may be important during the innate immune response to infection.
ABC of oral health: Oral health care for patients with special needs
Authors: R. Davies
Journal: BMJ (2000)

People with special needs are those whose dental care is complicated by a physical, mental, or social disability. They have tended to receive less oral health care, or of lower quality, than the general population, yet they may have oral problems that can affect systemic health. Improving oral health for people with special needs is possible mainly through community based dental care systems. Education of patients and parents or carers with regard to prevention and treatment of oral disease must be planned from an early stage. This will minimise disease and operative intervention since extractions and surgical procedures in particular often produce major problems. Dental healthcare workers also often need to be educated about this subject.



Appalling oral hygiene and periodontitis in a patient awaiting cardiac valvular surgery. Dental procedures involving gingival laceration or periodontal disruption (such as extraction) can produce bacteraemia of oral microorganisms, which could lead to infective endocarditis



In this context various conditions can lead to people needing special care, not least patients with dental phobias. Many of these patients can be treated with behavioural modification techniques, though a minority will require sedation or general anaesthesia.

This article concentrates on those who are medically compromised, mentally challenged, mentally ill, or socially excluded.



Erythematous candidiasis, presenting as a median rhomboid glossitis, is common in patients with immune defects



The commonest problems are in patients with a bleeding tendency or cardiovascular disease, or who are immunocompromised.

### Bleeding disorders

Dental extractions and surgical procedures, including local analgesic injections, can cause problems in patients treated with anticoagulant drugs and those with coagulation defects or severe thrombocytopenic states.

With patients treated with anticoagulant drugs, local analgesia and minor surgery (simple extractions of two or three teeth) may generally be carried out safely in general practice with no change in treatment if test results are …
Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment
Authors: Ray K. M. Leung, Kirsty Thomson, Awen Gallimore, Emma Jones, Maries Van den Broek, Sophie Sierro, Abdul-Razzak Alsheikhly, Andrew McMichael, Amin Rahemtulla
Journal: Nature Immunology (2001)
The radiance P-32 RDX balloon in saphenous vein grafts: A comparison of De-Novo and In-Stent restenotic lesions in the SVG brite trial
Authors: Costantino O. Costantini, Alexandra J. Lansky, Kazuyuki Shirai, Ecaterina Cristea, Horia Marginean, Cristina Ispas, Brian Proctor, Moses Tarawali, Mark G. Midei, Maurice Buchbinder, Roxana Mehran, George Dangas, Jeffrey M. Moses, Martin B. Leon, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2003)
Internal and external validity
Authors: P. Sedgwick
Journal: BMJ (2010)

A randomised controlled trial assessed the efficacy of a psychological intervention in improving the mother-infant relationship and security of infant attachment postpartum.1 A consecutive series of 452 women in their last trimester of pregnancy who were living in poverty in a crowded South African settlement were identified. All the women were invited to take part in the study, three of whom refused. The remaining women were randomly assigned to receive the intervention (n=220) or to a control group (n=229) that received no therapeutic input.

An analysis was conducted with data from …
Refining analyses of copy number variation identifies specific genes associated with developmental delay
Authors: Bradley P Coe, Kali Witherspoon, Jill A Rosenfeld, Bregje W M van Bon, Anneke T Vulto-van Silfhout, Paolo Bosco, Kathryn L Friend, Carl Baker, Serafino Buono, Lisenka E L M Vissers, Janneke H Schuurs-Hoeijmakers, Alex Hoischen, Rolph Pfundt, Nik Krumm, Gemma L Carvill, Deana Li, David Amaral, Natasha Brown, Paul J Lockhart, Ingrid E Scheffer, Antonino Alberti, Marie Shaw, Rosa Pettinato, Raymond Tervo, Nicole de Leeuw, Margot R F Reijnders, Beth S Torchia, Hilde Peeters, Brian J O'Roak, Marco Fichera, Jayne Y Hehir-Kwa, Jay Shendure, Heather C Mefford, Eric Haan, Jozef Gécz, Bert B A de Vries, Corrado Romano, Evan E Eichler
Journal: Nature Genetics (2014)
Gonadotropin-Releasing Hormone Receptors: Structure and Signal Transduction Pathways
Authors: STANKO S. STOJILKOVIC, JOHN REINHART, KEVIN J. CATT
Journal: Endocrine Reviews (1994)

SEVERAL aspects of the GnRH receptor and its signaling properties and secretory actions have been previously described (1–5). The characterization of GnRH receptors, their physiological regulation, and their relationship to reproductive function were discussed in 1981 (1). The role of Ca2+ as the second messenger, and of diacylglycerol (DAG) as a potential amplifier of the Ca2+ signaling in GnRHstimulated cells, was reviewed in 1986 (2). The molecular mechanism of GnRH action was further discussed in 1988, including the dependence of GnRH-induced secretion on phosphoinositide action (3, 4). Also, signal transduction in GnRH-stimulated cells was reviewed in 1990 as an example of a phospholipid-dependent pathway; the review addressed the interactions between cytoplasmic calcium and protein kinase C (PKC) in the control of gonadotropin synthesis and release, as well as the participation of phospholipase D (PLD), arachidonic acid (AA) and its metabolites in GnRHinduced signaling (5). Since 1990, there has been an explosive increase in information about GnRH receptors and their signaling properties.
Ranger Michael Whelan
Authors: T R Whelan
Journal: BMJ (2003)

Consultant anaesthetist Mid-Sussex Hospitals 1960-85 (b Birkenhead 1922; q Liverpool 1951; FFARCS, DA), d 13 October 2002.

Ranger was commissioned into the Indian army in 1942, and served with the Frontier Force Rifles (“Piffers”) on the North West Frontier, in Persia, and in the Middle East. He later emigrated to Canada for an internship in Edmonton, Alberta. However, finding the climate there even more grim than the postwar austerity in England, he returned, via New York and an idyllic year in Bermuda (where Ranger met John F Kennedy as a patient). After an anaesthetic course at Liverpool, he moved south via the Hammersmith, to Cuckfield and Haywards Heath Hospitals. Ranger was interested in languages and military history. He leaves a wife, Noreen; two children; and two grandchildren.
SOME PHASES OF BRONCHO-PNEUMONIA IN CHILDREN.Read in the Section on Diseases of Children, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: J. M. G. CARTER
Journal: JAMA (1893)

In France, England and the United States of America, broncho-pneumonia is usually reported in mortality tables as catarrhal pneumonia, capillary bronchitis or congestion of the lungs, and in a study of statistics this should be borne in mind and these terms included under the designation, broncho-pneumonia, at least until greater harmony in terminology prevails. It may sometimes be mistaken for acute bronchitis or pneumonia. That these mistakes are made is evidence of two things: 1, a possible carelessness in diagnosis; and 2, some confusion as to the precise pathologic condition termed broncho-pneumonia. It is certainly confusing to read some of the definitions given of this disease. If one is to understand the obstruction of a small bronchial tube and the resulting inflammation about it to be the special condition in broncho-pneumonia, then the autopsy would usually have to determine the diagnosis. If an inflammation of the connective tissue of the
Clarification of the Risk for Venous Thrombosis Associated with Hereditary Protein S Deficiency by Investigation of a Large Kindred with a Characterized Gene Defect
Authors: Rachel E. Simmonds
Journal: Annals of Internal Medicine (1998)

Background: Protein S is an important regulatory protein of the coagulation cascade. The risk for venous thrombosis associated with protein S deficiency has been uncertain because all previous risk estimates used phenotypic evaluation alone, which can be ambiguous. Objective: To quantitate the risk for thrombosis associated with a characterized protein S gene mutation that causes a Gly295→Val substitution and protein S deficiency. Design: Retrospective study of a single extended family. Setting: University hospital referral center. Participants: A 122-member protein S-deficient family, in which 44 members had a recently characterized gene defect. Measurements: Comprehensive history of thrombosis, history of exposure to acquired risk factors for thrombosis, levels of total and free protein S antigen, and genotype for the mutation causing the Gly295→Val substitution. Results: Kaplan-Meier analysis of thrombosis-free survival showed that the probability of remaining free of thrombosis at 30 years of age is 0.5 (95% CI, 0.33 to 0.66) for carriers of the Gly295→Val mutation compared with 0.97 (CI, 0.93 to 1.0) for normal family members (P < 0.001). In a multivariate Cox regression model that included smoking and obesity, the mutation was a strong independent risk factor for thrombosis (hazard ratio, 11.5 [CI, 4.33 to 30.6]; P < 0.001). For free (but not total) protein S antigen levels, the distributions of persons with and persons without the mutation did not overlap. Conclusions: Protein S deficiency, as defined by the presence of a causative gene mutation or a reduced level of free protein S antigen, is a strong independent risk factor for venous thrombosis in a clinically affected family.
Phototherapy: Targeting‐Triggered Porphysome Nanostructure Disruption for Activatable Photodynamic Therapy (Adv. Healthcare Mater. 8/2014)
Authors: Cheng S. Jin, Liyang Cui, Fan Wang, Juan Chen, Gang Zheng
Journal: Advanced Healthcare Materials (2014)

Porphysome is the most stable and efficient delivery system of porphyrins, but the nanostructure converts the singlet oxygen generation mechanism to a thermal ablation mechanism. On page 1240, by incorporating targeting ligands (e.g. folate) into porphysome formulation, G. Zheng, J. Chen, and co-workers show that receptor-mediated endocytosis facilitates the nanostructure disruption inside cells, which switches back on singlet oxygen generation of the densely packed porphyrins for effective photodynamic therapy (PDT).
Echocardiography in the Diagnosis of Hypoplasia of the Left or Right Ventricles in the Neonate
Authors: RICHARD A. MEYER, SAMUEL KAPLAN
Journal: Circulation (1972)

Echocardiographic studies were performed on six patients with autopsy-proved aortic atresia and hypoplastic left ventricle and two patients with surgically proved tricuspid atresia and hypoplastic right ventricle. The findings were compared to those from the echograms of 50 normal newborns who served as a control group. The ultrasound measurements obtained in the normal newborns were as follows: mean right ventricular end-diastolic dimension, 1.3 cm (range, 1.0 to 1.7), mean left ventricular end-diastolic dimension, 1.6 cm (range, 1.2 to 2.0), mean left atrial dimension, 0.9 cm (range, 0.6 to 1.3), and mean left ventricular outflow tract dimension, 1.0 cm (range, 0.7 to 1.2). The mean velocities of closure of the mitral and tricuspid valves during passive filling of the ventricles were 53 mm/sec and 43 mm/sec. The ranges were 36 to 80 mm/sec for the mitral valve and 34 to 56 mm/sec for the tricuspid valve. In the patients with aortic atresia, the significant findings were a larger than normal right ventricular chamber (mean, 2.5 cm), a left ventricular chamber measuring less than 0.9 cm, and an absent or grossly distorted mitral valve echo. By contrast the patients with tricuspid atresia had very small right ventricular dimensions less than 0.6 cm, no demonstrable tricuspid valve echo, and a larger than normal left ventricle (mean, 2.3 cm). The above findings were diagnostic and were not confused with the normal newborn or other forms of congenital heart disease.