tbuckley/cabot-search huggingface dataset:
Toll-like receptor-mediated control of HBV replication by nonparenchymal liver cells in mice
Authors: Jun Wu, Mengji Lu, Zhongji Meng, Martin Trippler, Ruth Broering, Agnes Szczeponek, Frank Krux, Ulf Dittmer, Michael Roggendorf, Guido Gerken, Joerg F. Schlaak
Journal: Hepatology (2007)

Hepatitis B virus (HBV) infection is one of the most frequent causes of chronic liver disease worldwide. Because recent studies have suggested that Toll-like receptor (TLR)-based therapies may be a promising approach in the treatment of HBV infection, we studied the role of the local innate immune system of the liver as a possible mediator of this effect. Murine nonparenchymal cells, including Kupffer cells (KCs) and sinusoidal endothelial cells (LSECs), were isolated from C57/BL6 wild-type or MyD88−/− mice and stimulated by agonists of TLR1 to TLR9. Supernatants were harvested and assayed for their antiviral activity against HBV in HBV-Met cells. No direct antiviral effect of TLR agonists could be observed. In controls (myeloid dendritic cells), TLR1, TLR3, TLR4, TLR7, and TLR9 activation lead to production of antiviral cytokines. By contrast, only supernatants from TLR3-stimulated and TLR4-stimulated KCs and TLR3-stimulated LSECs from wild-type mice were able to potently suppress HBV replication as assessed via Southern blotting. Similar results were found with cells from MyD88−/− mice, indicating that the effect was independent of this signaling pathway. Cellular HBV RNA and hepatitis B surface antigen or hepatitis B e antigen levels in supernatants remained unchanged. Using neutralizing antibodies, we demonstrated that the TLR3-mediated effect but not the TLR4-mediated effect is mediated exclusively through interferon-β. Conclusion: Our data indicate that the innate immune system of the liver can control HBV replication after activation by TLR agonists. This has implications for the development of TLR-based therapeutic approaches against HBV. (Hepatology 2007.)
Habituation and Addiction to Amphetamines
Authors: L. G. Kiloh, S. Brandon
Journal: BMJ (1962)

The group of amphetamine drugs has been available since 1935. Used at first for narcolepsy, they have since found a place in the treatment of barbiturate poisoning, nocturnal enuresis, epilepsy, behaviour disorders, neurasthenic and depressive syndromes, and post encephalitic Parkinsonism as well as such relatively normal states as fatigue when driving or in combat, obesity, and hangovers. The amphetamines in general are prescribed readily and light-heartedly, and indeed there is official support for such a practice. The Ministry of Health's Annual Report for 1954 included this statement :  The drugs of this group [that is, the amphetamines] have the advantage of being relatively non-toxic, addiction to them is rare, and there are no serious ill-effects ; they may therefore be given to out patients without undue risk. Leake (1958) states:  Gradually, as experience with the amphetamines has ripened they have become firmly established as versatile and helpful remedies given to millions of people and under such conditions as to offer remarkably low potential for causing harm or unwanted effects. In an answer given in the British Medical Journal (1961)  was noted that  true addiction to the ampheta mines probably does not occur, and that  there would appear to be no particular reason why this preparation should not be continued indefinitely  ; and Stungo (1961) states that a number of long-term studies have failed to reveal any evidence of either addiction or true habituation to the amphetamines, and later adds, it can accordingly be categorically stated that addiction or habituation to amphetamines alone is extremely rare. It is the purpose of this paper to demonstrate that these statements are dangerously inaccurate and that a considerable abuse of the amphetamines and of phen metrazine exists, habituation and addiction occurring very frequently in our society.
Providers to Advise of 'Medical Miranda'
Authors: Paul Cotton
Journal: JAMA (1991)

HEALTH CARE provider organizations are being ordered to advise patients of their rights to refuse care and to name proxies in case they become incompetent. The so-called medical Miranda warnings, explaining state law on living wills and durable powers of attorney for health care, will be the responsibility of all hospitals, nursing homes, health maintenance organizations (HMOs), hospices, and home health care agencies who want Medicare or Medicaid reimbursement as of November 1991. Officially known as the Patient Self-Determination Act, the law was part of an omnibus budget bill passed last November. It requires that providers Maintain written policies on refusal of care and advance directives Give this written information to adults at the time of admission as hospital inpatients or as residents of a skilled nursing facility, before coming under the care of a home health agency or hospice, or upon enrollment in an HMO Note in patient records
Location of phosphatidylethanolamine and phosphatidylserine in the human platelet plasma membrane.
Authors: P K Schick, K B Kurica, G K Chacko
Journal: Journal of Clinical Investigation (1976)

The location of phospholipids in the human platelet plasma membrane was probed with 2, 4, 6-trinitrobenzenesulfonate (TNBS). TNBS does not penetrate inintact cells and can label phosphatidylethanolamine (PE) and phosphatidylserine (PS). In tact platelets, PE is not accessible to TNBS during the initial 15 min. However, 6.9% PE reacts with TNBS after 30 min and 17.9% PE is labeled after 90 min. In intact platelets, PS is not labeled even after 2 h. In contrast, in phospholipids extracted from platelets 71% PE and 26.5% PS react with TNBS within 5 min. This indicates that PS is inaccessible and PE is relatively inaccessible to TNBS in intact platelets. After incubation of platelets with thrombin, there is increased labeling of PE but no labeling of PS. The incubation of platelets with thrombin (0.05 U/ml) for 5 min results in 16.2% increase of PE labeling during subsequent 30-min incubation with TNBS. PS does not appear to be a component of the functional surface of platelets. However, exposure of PE may have a critical role in platelet hemostatic function. The implication of the study is that there is asymmetry of phopholipids in the platelet plasma membrane which has considerable physiological significance.
The adoptive transfer of pregnancy-induced unresponsiveness to male skin grafts with thymus-dependent cells.
Authors: R N Smith, A E Powell
Journal: The Journal of Experimental Medicine (1977)

A majority of C57BL/10Sn females pregnant six or more times by syngeneic males do not reject male skin grafts. The pregnancy induced tolerance of male skin grafts was transferred adoptively to virgin recipients by thymus-dependent cells from multiparous tolerant donors.
IRF-1 Expression Is Essential for Natural Killer Cells to Suppress Metastasis
Authors: Antje Ksienzyk, Berit Neumann, Ramya Nandakumar, Katja Finsterbusch, Martina Grashoff, Rainer Zawatzky, Günter Bernhardt, Hansjörg Hauser, Andrea Kröger
Journal: Cancer Research (2011)

IFN-γ promotes tumoral immune surveillance, but its involvement in controlling metastases is less clear. Using a mouse model of pulmonary metastases, we show that local IFN-γ treatment inhibits formation of metastases through its regulation of IRF-1 in tumor cells. IRF-1 is an IFN-γ-induced transcription factor pivotal in the regulation of infection and inflammation. IRF-1 blockade abolished the inhibitory effect of IFN-γ on tumor metastases, whereas ectopic expression of IRF-1 phenocopied the inhibitory effects of IFN-γ. IRF-1 did not affect the survival of tumor cells in the circulation or their infiltration into lungs, but it was essential to support the pulmonary attraction and activation of natural killer (NK) cells. Depleting NK cells from mice abolished the protective effect of IFN-γ or IRF-1 on metastases. In addition, cytotoxicity assays revealed that tumor cells expressing IRF-1 were targeted more effectively by NK cells than IRF-1 nonexpressing tumor cells. Moreover, NK cells isolated from lungs inoculated with IRF-1-expressing tumor cells exhibit a greater cytotoxic activity. Mechanistic investigations revealed that IRF-1-induced NK cell cytotoxicity was independent of perforin and granzyme B but dependent on the NK cell activating receptor DNAM-1. Taken together, our findings establish IRF-1 as an essential mediator of the cross-talk between tumor cells and NK cells that mediate immune surveillance in the metastatic niche.
PSYCHOSES OCCURRING AMONG PSYCHOPATHIC PERSONALITIES IN ASSOCIATION WITH INELASTIC SITUATIONS OVERSEAS
Authors: HERBERT S. RIPLEY, STEWART WOLF
Journal: American Journal of Psychiatry (1948)

The present study is concerned with a group of 50 psychotic patients with psychopathic personalities, encountered in New Guinea and the Philippines during World War II. The heredity, environmental background, personality development, and psychopathology were investigated. Fifty psychopaths not considered to be psychotic were used as a control group. Among the 50 patients the family setting was characteristically insecure. Enuresis, nail biting, temper tantrums, and sleepwalking were common. The scholastic performance and school adjustment were poor. The work record was characterized by frequent shifts in jobs, periods of unemployment, and difficulty in getting along with fellow workers and employers. Difficulties in developing and maintaining satisfactory interpersonal relationships were also common. Over two-thirds of the patients had a record of from one to 30 military or civilian arrests. Sexual life was marked by promiscuity and poor marital adjustment. In 6 there was a history of homosexuality. Of the 24 who had been married, 14 were divorced or separated. In 24 cases there was evidence of a previous neurotic or psychotic illness. Twenty-two were alcoholic. Five were addicted to drugs. During the psychosis the commonest psychopathological features were excessive motor activity, depression, auditory and visual hallucinations, paranoid delusions, disorganization of thinking, bizarre behavior, and defective judgment. In 22 cases suicidal preoccupations were found. Ten had made suicidal attempts. The dynamic factors and type of reaction were similar to those found in prison psychosis.
The Cost Effectiveness of Stopping Preterm Labor with Beta-Adrenergic Treatment
Authors: Carol C. Korenbrot, Laura H. Aalto, Russell K. Laros
Journal: New England Journal of Medicine (1984)

Abstract We retrospectively compared the costs of maternal and neonatal medical care after beta-adrenergic drug treatment, given to arrest preterm labor, with expected costs associated with no gestational delay. The treatment arrested labor for at least three days in 61 per cent of patients; gestation was extended by 14.1±1.1 weeks (mean ±S.E.M.) in infants with the earliest gestational age at treatment (20 to 25 weeks) and by 2.3±0.7 weeks in those with the latest gestational age (36 to 37 weeks). Costs were based on hospital charges and physicians' fees, including high-risk obstetric outpatient charges, obstetric prenatal and delivery inpatient charges, and pediatric inpatient charges. Treatment provided between 26 and 33 weeks of gestation was clearly cost effective, resulting in expected savings of $11,240 (1981 dollars) per birth. After 33 weeks there was no substantial difference in expected costs with or without treatment. Between 20 and 25 weeks of gestation, the expected costs per surviving infant were $39,000 lower with treatment; however, the number of mothers who were not treated at this early stage of gestation (three patients) was too small to permit statistical significance. When the improved survival of infants after prenatal treatment was taken into account, treatment before 25 weeks was also cost effective. Thus, the increased costs of prenatal medical care were offset by decreased costs of neonatal medical care when treatment was given before 34 weeks of gestation. (N Engl J Med 1984; 310:691–6.)
Corequirement of PICK1 Binding and PKC Phosphorylation for Stable Surface Expression of the Metabotropic Glutamate Receptor mGluR7
Authors: Young Ho Suh, Kenneth A. Pelkey, Gabriela Lavezzari, Paul A. Roche, Richard L. Huganir, Chris J. McBain, Katherine W. Roche
Journal: Neuron (2008)
Government plans to revalidate doctors every five years
Authors: O. Dyer
Journal: BMJ (2008)

All doctors working in England are to face annual appraisal of their skills and performance and will have to reapply for a medical licence every five years, according to plans announced by the UK chief medical officer, Liam Donaldson.

For most doctors not in substantive training posts revalidation will involve two components—relicensing, subject to their adherence to generic standards, such as the General Medical Council’s Good Medical Practice guidelines, and specialist recertification, which will depend on meeting criteria to be set by the relevant medical royal colleges.

Both the GMC and the Academy of Royal Medical Colleges worked with Sir Liam to develop the proposals, which the GMC’s president, Graeme Catto, called “the biggest change to medical regulation in 150 years.”

Although GPs and some specialties already have appraisal systems written into their contracts, Sir Liam’s working group argued that implementation was …
KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype
Authors: A Clipson, M Wang, L de Leval, M Ashton-Key, A Wotherspoon, G Vassiliou, N Bolli, C Grove, S Moody, L Escudero-Ibarz, G Gundem, K Brugger, X Xue, E Mi, A Bench, M Scott, H Liu, G Follows, E F Robles, J A Martinez-Climent, D Oscier, A J Watkins, M-Q Du
Journal: Leukemia (2014)
Efficacy of camptothecin in progressive multifocal leucoencephalopathy
Authors: Seamus O'Reilly
Journal: The Lancet (1997)

In Juliane Vollmer-Haase and colleagues' report (May 10, p 1366),1Vollmer-Haase J Young P Ringelstein EB Efficacy of camptothecin in progressive multifocal leucoencephalopathy.Lancet. 1997; 349: 1366Summary Full Text Full Text PDF PubMed Scopus (34) Google Scholar the camptothecin agent used is incorrectly stated. On the basis of the dose and schedule used, and the reference to fluorouracil refractory colorectal cancer, the camptothecin analogue CPT-11 (Irinotecan) was evaluated and not camptothecin, the parent molecule. In the study by Kerr et al2Kerr DA Chang C-F Gordon J et al.Inhibition of human neurotropic virus (JVC) DNA replication in glial cells by camptothecin.Virol. 1993; 196: 612-618Crossref PubMed Scopus (53) Google Scholar which they cite, only camptothecin and topotecan (a commercially available camptothecin analogue used in the treatment of ovarian cancer) were tested for in-vitro activity against the JC virus. Neither CPT-11, nor its active metabolite SN-38, were assessed; consequently the basis for selecting CPT-11 in this study is unclear. The clinical development of the parent camptothecin drug ceased in the 1970s because of unpredictable haemorrhagic gastritis and cystitis due to poor drug solubility.3Slichenmyer WJ Rowinsky EK Donehower RC et al.The current status of the camptothecin analogues as anti-tumor agents.J Natl Cancer Inst. 1993; 85: 271-291Crossref PubMed Scopus (652) Google Scholar Although the agent is not commercially available, it is being evaluated in limited studies in the USA4Liehr JG Ahmed AE Giovanella BC Pharmacokinetics of camptothecins administration orally.Annal N York Acad Sci. 1996; 803: 157-163Crossref PubMed Scopus (15) Google Scholar and in China.5Xu B Chen J-T Yang J-L et al.New results in pharmacologic research of some anti-cancer agents.in: Burns JJ Tsuchitani PJ Proceedings of the US-China Pharmacologic Symposium. Committee on Scholarly Communication with the Peoples Republic of China. National Academy of Sciences, Washington DC1979: 151-158Google Scholar The doses evaluated in previous studies of camptothecin were lower than the doses recommended for CPT-11 treatment (90–180 mg/m2Kerr DA Chang C-F Gordon J et al.Inhibition of human neurotropic virus (JVC) DNA replication in glial cells by camptothecin.Virol. 1993; 196: 612-618Crossref PubMed Scopus (53) Google Scholar vs 350 mg/m2Kerr DA Chang C-F Gordon J et al.Inhibition of human neurotropic virus (JVC) DNA replication in glial cells by camptothecin.Virol. 1993; 196: 612-618Crossref PubMed Scopus (53) Google Scholar).3Slichenmyer WJ Rowinsky EK Donehower RC et al.The current status of the camptothecin analogues as anti-tumor agents.J Natl Cancer Inst. 1993; 85: 271-291Crossref PubMed Scopus (652) Google Scholar Therefore, the accidental use of camptothecin at the dose evaluated in Vollmer-Haase's case report could lead to important toxicities. Efficacy of camptothecin in progressive multifocal leucoencephalopathyAuthors' reply Full-Text PDF
Structural, functional, and tissue distribution analysis of human transferrin receptor-2 by murine monoclonal antibodies and a polyclonal antiserum
Authors: Silvia Deaglio, Andrea Capobianco, Angelita Calı̀, Francesca Bellora, Federica Alberti, Luisella Righi, Anna Sapino, Clara Camaschella, Fabio Malavasi
Journal: Blood (2002)
The Pathogenesis of Venous Limb Gangrene Associated with Heparin-Induced Thrombocytopenia
Authors: Theodore E. Warkentin
Journal: Annals of Internal Medicine (1997)

Background: Platelet-mediated arterial occlusion is a well-recognized cause of limb loss in patients with heparin-induced thrombocytopenia. However, the syndrome of distal ischemic necrosis complicating the deep venous thrombosis (venous limb gangrene) sometimes associated with heparin-induced thrombocytopenia has not been well characterized. Objective: To study the pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia. Design: Characterization (based on descriptive and case–control studies) of a novel syndrome of limb loss and hypothesis testing by analysis of plasma samples. Setting: Five university-associated hospitals in one medical community. Patients: Clinical and laboratory records of 158 patients with heparin-induced thrombocytopenia were reviewed to identify patients with venous limb gangrene (n = 8), limb arterial thrombosis (n = 10), and uncomplicated deep venous thrombosis (n = 58). Measurements: Clinical and laboratory factors associated with venous limb gangrene, including thrombin-antithrombin complexes and vitamin K-dependent procoagulant and anticoagulant factors. Results: Warfarin treatment was more frequently associated with venous limb gangrene than with limb arterial thrombosis (8 of 8 patients compared with 3 of 10 patients; P = 0.004). The anticoagulant effect of warfarin seemed greater in the 8 patients with venous limb gangrene than in the 58 patients who did not develop gangrene (median international normalized ratio, 5.8 compared with 3.1; P < 0.001). Compared with plasma from controls, plasma from patients with venous limb gangrene had a higher ratio of thrombin-antithrombin complex to protein C activity during warfarin treatment. No hereditable abnormalities of the protein C anticoagulant pathway were seen in any patient. Conclusions: Warfarin treatment of deep venous thrombosis associated with heparin-induced thrombocytopenia is a possible cause of venous limb gangrene, perhaps because of acquired failure of the protein C anticoagulant pathway to regulate thrombin generation.
Abstract 4896: Real-time imaging of pancreatic cancer stem cells for identification of the selectively targeting therapy.
Authors: Shinji Tanaka, Rama Adikrisna, Satoshi Matsumura, Daisuke Ban, Takanori Ochiai, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Shoji Yamaoka, Shigeki Arii
Journal: Cancer Research (2013)

Abstract Identification and purification of cancer stem cells (CSCs) should offer a clue of the therapeutic targets, but their heterogeneous expansion remains the significant obstacle of studies. One of the solutions might be establishment of real-time monitoring of CSC, based on fluorescence imaging with the intrinsically low proteasome activity. The monitoring system in human pancreatic cancer cells proved directly the asymmetric division of CSC to generate non-CSC. Real-time chemoresistance of the CSCs and remarkable tumorigenicity (as few as 10 cells) indicated their preclinical significance. The synthetic lethal screening was applied to identify a novel compound targeting specifically the pancreatic CSCs. It inhibited nuclear accumulation of beta-catenin in the pancreatic CSCs. Anti-CSC effects of the compound were confirmed by in vitro dynamic images and in vivo tumor analyses. The real-time monitoring system of CSCs is an innovative strategy providing a visible target that should lead to the discovery of successful therapies directed toward CSCs of aggressive cancers. Citation Format: Shinji Tanaka, Rama Adikrisna, Satoshi Matsumura, Daisuke Ban, Takanori Ochiai, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Shoji Yamaoka, Shigeki Arii. Real-time imaging of pancreatic cancer stem cells for identification of the selectively targeting therapy. [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 4896. doi:10.1158/1538-7445.AM2013-4896 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Disposable syringes for insulin injection.
Authors: A Greenough, P M Cockcroft, A Bloom
Journal: BMJ (1979)

Results of a questionnaire on use of glass syringes among diabetic patients showed considerable variation in methods of keeping the syringes and in the duration of their useful life. Thirty patients took part in an investigation in which each patient used the same disposable syringe in place of the glass syringe for up to two months. No clinical or bacteriological evidence of infection was found. Used in this way, disposable syringes were less expensive than glass syringes. They are lighter than glass syringes, less susceptible to damage, and more easily carried on journeys.
What a doctor is good for
Authors: D. Loxterkamp
Journal: BMJ (2014)

With growing numbers of physician assistants and nurse practitioners, what do doctors add?

Over the years I have served as both a preceptor and colleague for more than a dozen physician assistants and nurse practitioners. All the while I wondered: are they as good as they seem, and are doctors as indispensable as we’d like to believe? When my daughter became a physician assistant I was forced to respond.

I share a small practice with six family physicians. Each of us works closely with a designated medical assistant. Around us, personal service representatives greet our patients and schedule their visits; billing associates ensure our financial survival. We also rely on a physical therapist, pharmacist, behavioral therapist, triage nurse, care manager, health coach, laboratory technician, medical records clerk, clinical coordinator, and practice director. Thus, you can forgive the doctor, let alone his or her patients, for sometimes getting lost in the shuffle.

Increasingly, advanced nurse practitioners and physician assistants will join the clinical team. One of each is now on our staff. In the United States, more than 165 training programs have …
How "malignant" is the neuroleptic malignant syndrome?
Authors: M F Bristow, D Kohen
Journal: BMJ (1993)

How "malignant" is the neuroleptic malignant syndrome?In early mild cases it may not be malignant at all Although cases of acute fatal psychoses associated with fever and neuromuscular disturbance have been reported sporadically since the nineteenth century' and the propensity for neuroleptic drugs to disrupt neuromuscular function has been described as their use has grown, the entity of the "neuroleptic malignant syndrome" is a comparatively recent phenomenon, mentioned in standard British psychiatric textbooks only for the past decade.In its brief lifespan it has generated considerable controversy with regard to its prevalence, diagnostic criteria, and management.A recent review estimated that the prevalence of the syndrome varied from 0.02% to 2% of admissions to acute