tbuckley/cabot-search huggingface dataset:
Transport characteristics of three fluorescent conjugated bile acid analogs in isolated rat hepatocytes and couplets
Authors: Lilia M. Maglova, Angela M. Jackson, Xue-Jun Meng, Michael W. Carruth, Claudio D. Schteingart, Huong-Thu Ton-Nu, Alan F. Hofmann, Steven A. Weinman
Journal: Hepatology (1995)

The transport properties of three different synthetically prepared fluorescent conjugated bile acid analogs (FBA), all with the fluorophore on the side chain, were determined using isolated rat hepatocytes and hepatocyte couplets. The compounds studied were cholylglycylamidofluorescein (CGamF), cholyl(N epsilon-nitrobenzoxadiazolyl [NBD])-lysine (C-NBD-L), and chenodeoxycholyl-(N epsilon-NBD)-lysine (CDC-NBD-L). When hepatocytes were incubated at 37 degrees C with 0.3 mumol/L of FBA and 0.15 mol/L of Na+, cell fluorescence increased linearly with time at a rate (U/min) of 7.8 +/- 0.5 for CGamF, 7.2 +/- 0.3 for C-NBD-L, and 13.7 +/- 1.0 for CDC-NBD-L (mean, +/- SE; n = 40 to 90). Uptake was concentration dependent for concentrations less than 20 mumol/L and was saturable. The Michaelis constant (Km) value (mumol/L) for CGamF was 10.8, for C-NBD-L was 3.8, and for CDC-NBD-L was 3.0. In the absence of Na+, the uptake rate was decreased by 50% for CGamF and by 38% for C-NBD-L; but uptake of CDC-NBD-L was unchanged and thus Na+ independent. Cellular uptake of all three derivatives was specific to hepatocytes and was absent in several nonhepatocyte cell lines. For CGamF and C-NBD-L, both Na(+)-dependent and Na(+)-independent uptake was inhibited by 200-fold excess concentrations of cholyltaurine, dehydrocholyltaurine, and cholate, but for CDC-NBD-L, these nonfluorescent bile acids did not inhibit initial uptake. The intracellular fluorescence of CGamF was strongly pH dependent at an excitation wavelength of 495 nm, but pH independent at 440 nm excitation. In contrast, intracellular fluorescence of C-NBD-L and CDC-NBD-L was pH independent. All three FBA were secreted into the canalicular space of approximately 50% to 60% of couplets. Cellular adenosine triphosphate (ATP) depletion with either CN- or atractyloside inhibited secretion of all three FBA. The multispecific organic anion transporter (MOAT) inhibitor, chlorodinitrobenzene, blocked secretion of fluorescent MOAT substrates at a concentration of 1 mumol/L. At this concentration it did not affect secretion of the three FBA. At higher concentrations, chlorodinitrobenzene partially inhibited the canalicular secretion of CGamF but not the other two FBA. In conclusion, all three FBA are secreted by canalicular membrane bile acid transporters, but the sinusoidal uptake characteristics of CGamF and C-NBD-L are more similar than those of CDC-NBD-L to the transport properties of cholyltaurine. Therefore, C-NBD-L appears to be the best of the three for studies of conjugated trihydroxy-bile acid transport in hepatocytes.
IMPACT OF PERCUTANEOUS CORONARY INTERVENTION FOR CHRONIC TOTAL OCCLUSION IN ELDER PATIENTS
Authors: Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Yoonjee Park, Sunki Lee, Ji Bak Kim, Sung Il Im, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2014)
Upper Respiratory Tract Carriage of Gram-Negative Enteric Bacilli by Hospital Personnel
Authors: James J. Rahal
Journal: JAMA (1970)

Nose and throat cultures were taken from 70 members of a hospital surgical staff. The incidence of upper respiratory tract colonization by gram-negative bacilli was not different than that among personnel having no patient contact. The antibiotic sensitivity of isolates from the surgical staff showed less resistance than those from wound infections. The results suggest that nasal and pharyngeal carriage of gram-negative enteric bacilli by medical personnel is not an important means by which infections are transmitted within the hospital.
Drug misusers: whose business is it?
Authors: M. Farrel, C. Gerada
Journal: BMJ (1997)

All indicators of illicit drug dependence have continued to climb over the past two decades, showing no sign of reversal. The one success has been the containment of HIV: through the provision of community services and the promotion of needle exchanges Britain has maintained one of the lowest HIV seroprevalence rates among injecting drug users globally.1 The increasing tide of drug misuse has, however, continued to place additional burdens on public services, from the criminal justice system to health and social services.2 How medical services should respond to drug dependence and its associated harms, and in particular which doctors should be responsible, is currently the subject of debate.

In his personal view in this issue Scott argues that psychiatrists have neither the skills or the attitudes appropriate to looking after drug misusers and that general practitioners are far better at it (p 613).3 Primary care services are often the first port of call for users …
US medical liability crisis spurs doctors walkouts and rallies
Authors: F. Charatan
Journal: BMJ (2003)

Four hospitals in West Virginia were forced to transfer patients to hospitals in other states earlier this month after more than two dozen surgeons stopped work in protest against soaring malpractice insurance premiums.

Their action, part of a growing protest movement in the United States by doctors angry about their insurance premiums, coincided with a strike in France by obstetricians and gynaecologists over the same issue (11 January, p 68). Doctors in many western countries are finding it increasingly hard to meet the cost of malpractice insurance.

“My malpractice rates are higher than any other physician's for the same practice in any other state in the union,” said …
Epicardial Substrate and Outcome With Epicardial Ablation of Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia
Authors: Fermin C. Garcia, Victor Bazan, Erica S. Zado, Jian-Fang Ren, Francis E. Marchlinski
Journal: Circulation (2009)

Efficacy of endocardial ventricular tachycardia (VT) ablation in arrhythmogenic right ventricular cardiomyopathy/dysplasia may be limited by epicardial VT, right ventricular thickening, or both. We sought to characterize the endocardial versus epicardial substrate, measure right ventricular free wall thickness, and determine epicardial ablation efficacy in patients with right ventricular cardiomyopathy/dysplasia.Thirteen consecutive patients (3 female; aged 43+/-15 years; range, 17 to 70 years) undergoing endocardial and epicardial sinus rhythm voltage mapping and epicardial VT ablation after failed endocardial VT ablation were included. In each patient, the low bipolar voltage area (<1.0 mV for epicardium and <1.5 mV for endocardium) was more extensive on the epicardium (95+/-47 versus 38+/-32 cm(2); P<0.001) and was uniformly marked by multicomponent and late electrograms. The basal right ventricular thickness assessed by electroanatomic map was >10 mm in 6 of 13 patients compared with 5 to 10 mm in 4 reference patients without structural disease. Twenty-seven VTs were targeted on the epicardium with the use of activation, entrainment, or pace mapping with focal/linear ablation and targeting of late potentials. Epicardial VTs were targeted opposite normal endocardium in 10 patients (77%) and/or opposite ineffective endocardial ablation sites in 11 patients (85%). During 18+/-13 months, 10 of the 13 patients (77%) had no VT, with 2 patients having only a single VT at 2 and 38 months, respectively.Patients with right ventricular cardiomyopathy/dysplasia and VT after endocardial ablation have a more extensive epicardial area of electrogram abnormalities and frequently have basal right ventricular wall thickening. Epicardial substrate and VT mapping identifies targets, and ablation results in VT control.
Why the “Appraisal of Guidelines for Research and Evaluation” Instrument Can and Should Further Inform Ethics Policy Work
Authors: Daniel Strech, Jan Schildmann
Journal: The American Journal of Bioethics (2012)

We agree with Frolic and colleagues (2012) that “it is imperative that HECs and ethicists develop clearer roles, responsibilities, procedural standards, and evaluation methods to ensure the deliver...
THE CULTURE OF WHOLE ORGANS
Authors: Alexis Carrel
Journal: The Journal of Experimental Medicine (1937)

1. A technique has been developed for the transplantation of the whole thyroid into the Lindbergh pump, and its perfusion, without the occurrence of infection, emboli, and other complications. 2. The gland remains alive during the period of perfusion, which lasted from 3 to 21 days. 3. The technique is simple enough to be used as a routine procedure for physiological or pathological studies of the thyroid gland.
Klebsiella pneumoniae and acute anterior uveitis in ankylosing spondylitis.
Authors: R Ebringer, D Cawdell, A Ebringer
Journal: BMJ (1979)

Klebsiella pneumoniae and acute anterior uveitis in ankylosing spondylitisAcute anterior uveitis (AAU) is frequently associated with ankylosing spondylitis (AS).It is probably not a complication of AS as it may often manifest before the onset of the disease.Acute anterior uveitis also occurs in Reiter's disease, ulcerative colitis, and Crohn's disease.When sacroiliitis is present, all of these conditions are strongly associated with the HLA B27 antigen.'The incidence of HLA B27
Mortality after <i>Staphylococcus aureus</i> bacteraemia in two hospitals in Oxfordshire, 1997-2003: cohort study
Authors: David H Wyllie, Derrick W Crook, Tim E A Peto
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To determine the incidence of methicillin resistant and methicillin sensitive <i>Staphylococcus aureus</i> (MRSA and MSSA) bacteraemia in inpatients and associated mortality within 30 days after diagnosis. <b>Design</b> Anonymised record linkage study of data from hospital information systems and microbiology databases. <b>Setting</b> Teaching hospital and district general hospital in Oxfordshire. <b>Participants</b> Inpatients aged 18 or over admitted to a teaching hospital between 1 April 1997 and 31 March 2004 and to a district general hospital between 1 April 1999 and 31 March 2004. The main part of the study comprised 216 644 inpatients; patients admitted to haematology, nephrology, or oncology services were not included because most were managed as outpatients. <b>Outcome measures</b> Nosocomial MSSA and MRSA bacteraemia; death in hospital within 30 days after bacteraemia. <b>Results</b> Rates of <i>S aureus</i> bacteraemia rose between 1997 and 2003, and MRSA was responsible for this increase. Overall mortality 30 days after bacteraemia was 29%. The crude odds ratio for death after MRSA bacteraemia compared with MSSA bacteraemia was 1.49 (95% confidence interval 0.99 to 2.26). <b>Conclusion</b> The spread of MRSA has greatly increased the overall number of cases of <i>S aureus</i> bacteraemia and has contributed to short term mortality after <i>S aureus</i> bacteraemia.
PFI contributes to large deficits of Scottish health boards
Authors: Bryan Christie
Journal: BMJ (2006)

Money will have to be diverted from patient care throughout the United Kingdom to pay for hospitals constructed under the government's controversial private finance initiative (PFI), a report from the University of Edinburgh has warned. 

It says that the schemes (now known as public-private partnerships) are already a key factor in NHS deficits and that this problem will escalate as more of these projects are completed. Under PFI, the private sector builds and pays for new hospitals and other healthcare facilities. In return, the NHS pays an annual charge to the private sector—often for 30 years or more. 

The study …
Abstract 1041: Sorafenib in combination with rottlerin show an additive effects in renal cell carcinoma (RCC) cells.
Authors: Matthias W. Joeckel, Elke Schneider, Frederik C. Roos, Christian Hampel, Joachim W. Thueroff, Walburgis Brenner
Journal: Cancer Research (2013)

Abstract Introduction: RCC is a tumor entity with poor outcome. Targeted therapies with tyrosine kinase inhibitors (TKI) are promising agents for combating progression in RCC. We investigated the effect of the TKI sorafenib and sunitinib on cancer progression in vitro. We additionally analysed a coadministration of rottlerin, inhibiting PKCdelta, with sorafenib or sunitinib. Methods: Four clear cell RCC cell lines were treated with sorafenib or sunitinib alone (5 μM) or in combination with rottlerin (10 μM). Proliferation (BrdU incorporation), apoptosis (caspase 3) and expression of PKCdelta in nuclei (pro-apoptitic), cytoplasm (inactive) and membranous (active) was quantified. The activity of PKCdelta was analysed by detection of phosphorylated PKCdelta (Western blot). Results: Cell proliferation was reduced by sorafenib and rottlerin, but not by sunitinib. Combination of sorafenib and rottlerin showed an additive effect in proliferation inhibition. Rottlerin and sunitinib induced apoptosis. Althougth sorafenib alone did not induce apoptosis, in combination with rottlerin, apoptosis was more intensely induced than with rottlerin alone. All agents induced an enhanced expression of PKCdelta in the nuclei. Sunitinib in combination with rottlerin reduced membrane -bound PKCdelta. Analogue, expression of activated PKCdelta was reduced after cell treatment with sunitinib in combination with rottlerin. Conclusion: Coadministration of sorafenib and rottlerin showed an additive effect on proliferation and apoptosis of RCC cells. The expression and activity of PKCdelta was reduced most by sorafenib in comibation with rottlerin. This indicates an improvement in RCC therapy with sorafenib by coadministration of rottlerin. Citation Format: Matthias W. Joeckel, Elke Schneider, Frederik C. Roos, Christian Hampel, Joachim W. Thueroff, Walburgis Brenner. Sorafenib in combination with rottlerin show an additive effects in renal cell carcinoma (RCC) cells. [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 1041. doi:10.1158/1538-7445.AM2013-1041
Impact of <i>IDH1</i> R132 Mutations and an <i>IDH1</i> Single Nucleotide Polymorphism in Cytogenetically Normal Acute Myeloid Leukemia: SNP rs11554137 Is an Adverse Prognostic Factor
Authors: Katharina Wagner, Frederik Damm, Gudrun Göhring, Kerstin Görlich, Michael Heuser, Irina Schäfer, Oliver Ottmann, Michael Lübbert, Wolfgang Heit, Lothar Kanz, Günter Schlimok, Aruna A. Raghavachar, Walter Fiedler, Hartmut H. Kirchner, Wolfram Brugger, Manuela Zucknick, Brigitte Schlegelberger, Gerhard Heil, Arnold Ganser, Jürgen Krauter
Journal: Journal of Clinical Oncology (2010)

We assessed the prognostic impact of IDH1 R132 mutations and a known single nucleotide polymorphism (SNP) located in the same exon of the IDH1 gene in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers.IDH1 exon four was directly sequenced in 275 CN-AML patients from two subsequent AML multicenter treatment trials and 120 healthy volunteers. Moreover, mutations in NPM1, FLT3, CEBPA, and WT1 were analyzed, and mRNA expression of IDH1 was quantified.IDH1 R132 mutations were found in 10.9% of CN-AML patients. IDH1 SNP rs11554137 was found in 12% of CN-AML patients and 11.7% of healthy volunteers. IDH1 R132 mutations had no impact on prognosis. In contrast, IDH1 SNP rs11554137 was an adverse prognostic factor for overall survival in univariate and multivariate analysis. Other significant factors were age, NPM1/FLT3 mutational status, WT1 SNP rs16754, and platelet count. The impact of IDH1 SNP rs11554137 was most pronounced in the NPM1/FLT3 high-risk patients (either NPM1 wild-type or FLT3-internal tandem duplication positive). Patients with IDH1 SNP rs11554137 had a higher expression of IDH1 mRNA than patients with two wild-type alleles.IDH1 SNP rs11554137 but not IDH1 R132 mutations are associated with an inferior outcome in CN-AML.
NHS hospitals set to make overall loss for first time since 2006
Authors: M. Limb
Journal: BMJ (2014)

NHS hospitals are set to make a loss of nearly £250m (€300m; $410m) by the end of this financial year, and experts have warned that budgets are coming under greater strain.

David Flory, chief executive of the NHS Trust Development Authority, has warned in papers to its board that the deficits were “very worrying” and posed a “very significant risk to the sustainability of the sector.”

In all, 26 NHS trusts of the 102 that do not have foundation status are forecast to be in the red at the end of March, posting a combined deficit of £457m. Some 76 trusts are expecting to at least break even, and …
EFFECTS OF ALCOHOL.
Authors: P. H. Cronin
Journal: JAMA (1884)

<h3>To the Editor:</h3><h3>Your first question:</h3> — "How does it happen that during its presence (that of alcohol), not only the products of combustion, but the sum total of all eliminations are diminished?" is premised upon a subtly devised sophism, and by the right of discovery I claim the opportunity thus afforded me—and with such an antagonist I may not soon find another—of asking, what proof can you bring forward in support of the assertion evidently conveyed by the question? Neither in lecture nor communication, have I attempted to show that the temperature of the body could be raised or lowered by the exhibition of alcohol. True, you mention that Anstie noticed a lowering of the temperature, and as you are no doubt well aware, this was in cases where complete stupor, or a condition of anæsthesia had been reached. As having a special bearing on this point, the investigations
Linkage of rheumatoid arthritis with HLA.
Authors: C M Deighton, P J Kelly, D J Walker
Journal: Annals of the Rheumatic Diseases (1993)

Endocytosis overshoot, which retrieves more membrane than vesicles just being exocytosed, occurs at nerve terminals and non-neuronal secretory cells. The mechanism that retrieves the overshoot membrane pool and the role of this pool remain largely unknown. We addressed this issue at the rat calyx of Held nerve terminal with capacitance measurements. We found that every calyx contained an overshoot pool ∼1.8 times the readily releasable pool. Retrieval of this pool required large calcium influx, and was inhibited by blockers of calcium/calmodulin-activated calcineurin and dynamin, suggesting the involvement of calcineurin and dynamin in endocytosis overshoot. Depletion of the overshoot pool slowed down compensatory endocytosis, whereas recovery of the overshoot pool via exocytosis that deposited stranded vesicles to the plasma membrane led to recovery of compensatory endocytosis, suggesting that the overshoot pool enhances endocytosis efficiency. These results suggest that the overshoot pool exists at every nerve terminal, is of limited size arising from vesicles stranded at the plasma membrane, is retrieved via calcium/calmodulin/calcineurin and dynamin signaling pathway, and can enhance endocytosis efficiency. Potential mechanisms for how the endocytosis overshoot pool enhances endocytosis efficiency are discussed.
Effect of Chronic Treatment With the Inducible Nitric Oxide Synthase Inhibitor <i>N</i> -Iminoethyl- <scp>l</scp> -Lysine or With <scp>l</scp> -Arginine on Progression of Coronary and Aortic Atherosclerosis in Hypercholesterolemic Rabbits
Authors: Delphine Behr-Roussel, Alain Rupin, Serge Simonet, Edith Bonhomme, Sophie Coumailleau, Alex Cordi, Bernard Serkiz, Jean-Noël Fabiani, Tony J. Verbeuren
Journal: Circulation (2000)

Background —We examined the implications of iNOS in atherosclerosis progression using the selective inducible NO synthase (iNOS) inhibitor N -iminoethyl- l -lysine (L-NIL) in hypercholesterolemic rabbits. Methods and Results —Nine rabbits were fed a 0.3% cholesterol diet for 24 weeks (Baseline group); 25 animals were maintained on the diet and treated for 12 extra weeks with L-NIL (5 mg · kg − 1 · d − 1 , L-NIL group, n=8), vehicle (Saline group, n=9), or l -arginine (2.25%, L-Arg group, n=8). In abdominal aortas of Saline rabbits, the lesions (53.7±5.7%, Baseline) increased to 75.0±5.0% ( P &lt;0.05) but remained unaltered in the L-NIL group (63.4±6.6%). Similar results were obtained for the intima/media ratio in thoracic aortas. In coronary arteries, the intima/media ratio was comparable in Baseline (0.68±0.18) and Saline (0.96±0.19) rabbits but decreased to 0.34±0.19 ( P &lt;0.05) in L-NIL rabbits. l -Arginine had beneficial effects only in abdominal aortas. An increased thoracic aorta collagen content was found in Saline and L-Arg but not in L-NIL rabbits. In thoracic aortas of the Saline group, acetylcholine caused modest relaxations that slightly increased by l -arginine but not by L-NIL. Relaxations to nitroglycerin were ameliorated by L-NIL. Conclusions —This is the first study showing that chronic treatment with an iNOS inhibitor, L-NIL, limits progression of preexisting atherosclerosis in hypercholesterolemic rabbits. Increased intimal collagen accumulation may participate in iNOS-induced atherosclerosis progression.
Evidence of vitamin E deficiency in patients with malabsorption or alcoholism and the effects of therapy.
Authors: M S Losowsky, P J Leonard
Journal: Gut (1967)

<h3>Introduction</h3> Most anal cancers are associated with HPV, particularly HPV 16. The incidence of anal cancer is increased among men who have sex with men (MSM) compared with the general population. Screening and treatment of anal intraepithelial neoplasia (AIN), the anal cancer precursor, are not yet standard of care, and prevention efforts are needed to reduce the incidence of anal cancer. We tested the quadrivalent HPV vaccine to determine its ability to reduce the incidence of AIN/anal cancer. <h3>Methods</h3> 598 MSM aged 16–26 years with five or fewer lifetime sex partners were randomised to receive vaccine or placebo at enrolment, month 2 and month 6. Subjects underwent detailed anogenital exams and HPV sampling from the penis, scrotum, perineal/perianal and anal canal at enrolment, month 7 and at 6-month intervals afterwards. Efficacy analyses were performed in a per-protocol (PPE) population (sero-negative and DNA-negative from day 1 through month 7 to the relevant vaccine HPV type) and in all enrolees in an intent-to treat (ITT) analysis. Median follow-up of the PPE population was 2.5 years (post-dose 3). <h3>Results</h3> Vaccine efficacy against HPV 6/11/16/18-related AIN and anal cancer in the PPE population was 77.5% (95% CI 39.6 to 93.3) (5 vaccine cases vs 24 placebo cases). Efficacy against high-grade AIN (AIN 2+) was 74.9% (95% CI 8.8 to 95.4). In the ITT population the efficacy was 50.3% (95% CI 25.7 to 67.2) and 54.2% (95% CI 18.0 to 75.3), respectively. No anal cancer was seen in either treatment group. <h3>Conclusions</h3> These results demonstrate that the quadrivalent HPV vaccine is efficacious in preventing AIN related to HPV 6/11/16/18 in MSM subjects naïve to vaccine HPV types at enrolment, as well as in an ITT population. The quadrivalent HPV vaccine may be a useful measure to reduce the incidence of anal disease in at-risk populations.
ITGB2 mutation combined with deleted ring 21 chromosome in a child with leukocyte adhesion deficiency
Authors: Maurilia Fiorini, Giovanna Piovani, Richard F. Schumacher, Chiara Magri, Valeria Bertini, Evelina Mazzolari, Lucia Notarangelo, Luigi D. Notarangelo, Sergio Barlati
Journal: Journal of Allergy and Clinical Immunology (2009)