tbuckley/cabot-search huggingface dataset:
Intracellular Ca <sup>2+</sup> Increases the Mitochondrial NADH Concentration During Elevated Work in Intact Cardiac Muscle
Authors: Rolf Brandes, Donald M. Bers
Journal: Circulation Research (1997)

It is not clear how mitochondrial energy production is regulated in intact tissue when energy consumption suddenly changes. Whereas mitochondrial [NADH] ([NADH] m ) may regulate cellular respiration rate and energetic state, it is not clear how [NADH] m itself is controlled during increased work in vivo. We have varied work and [Ca 2+ ] in intact cardiac muscle while assessing [NADH] m using fluorescence spectroscopy. When increased work was accompanied by increasing average [Ca 2+ ] c (by increasing [Ca 2+ ] o or pacing frequency), [NADH] m initially fell and subsequently recovered to a new steady state level. Upon reduction of work, [NADH] m overshot and then returned to control levels. In contrast, when work was increased without increasing average [Ca 2+ ] c (by increasing sarcomere length), [NADH] m fell similarly, but no recovery or overshoot was observed. This Ca 2+ -dependent recovery and overshoot may be attributed to Ca 2+ -dependent stimulation of mitochondrial dehydrogenases. We conclude that the immediate initial increase in respiration rate upon elevation of work is not activated by increased [NADH] m (since [NADH] m rapidly fell) or by [Ca 2+ ] c (since work could also be increased at constant [Ca 2+ ] c ). However, during sustained high work, a Ca 2+ -dependent mechanism causes slow recovery of [NADH] m toward control values. This demonstrates a Ca 2+ -dependent feed-forward control mechanism of cellular energetics in cardiac muscle during increased work.
Mycosis fungoides: the addition of concurrent and adjuvant interferon to total skin electron beam therapy
Authors: A.E. Wagner, D. Wada, G. Bowen, D.K. Gaffney
Journal: British Journal of Dermatology (2013)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Mycosis fungoides (MF) is a malignant T‐cell disorder involving the skin. The behaviour of MF is dichotomous, with a limited impact and an excellent prognosis for early‐stage patients.1 In contrast, later‐stage patients demonstrate median survival times ranging from only 1 year to 4 years with persistent disease progression.2 3 Total skin electron beam therapy (TSEBT) demonstrates excellent response but progression is common, and the combination of TSEBT with other systemic agents has failed to show significant improvements in disease control.4 5 The combination of TSEBT with interferon has not been well studied, but holds theoretical promise. This prompted us to investigate our institutional experience of treatment for MF with TSEBT, and to evaluate the effect of concurrent and adjuvant interferon. All patients who had a pathologically confirmed diagnosis of MF treated with TSEBT from 1988 to 2011 were included. Data were retrospectively collected regarding patient and disease characteristics. Follow‐up was scheduled for every 3–4 months, and response to treatment was determined within 1 month of treatment completion, classified as either a complete response (eradication of all visible lesions) or a partial response (visible lesions remaining). Recurrences were confirmed pathologically with a skin biopsy, or by initiation of new treatment.
TCT-212 Efficacy of the Novel BioMime Sirolimus-Eluting Stents with a Biodegradable Polymer in the Treatment of De Novo Coronary Lesions: An Angiographic Subanalysis of the Combined meriT-1 and meriT-2 Prospective Clinical Trials
Authors: Ricardo A. Costa, Alexandre Abizaid, Sameer Dani, Hasit Joshi, Gurpreet S. Wander, Suhas Hardas, Suresh Vijan, Thomas Alexander, Sunita Abraham, Manjunath N. Cholenahally, Prabhakar Shetty, Upendra Kaul, Ashok Seth
Journal: Journal of the American College of Cardiology (2013)
GPs are angry over pay for primary care groups
Authors: L. Beecham
Journal: BMJ (1998)

Representatives of GPs in England are angry at the levels of pay that the Department of Health has agreed for doctors who sit on the boards of primary care groups (PCGs).

According to the health circular issued this week, GP chairs of boards will be paid between £13225 ($21160) and £15125 for two to four days a week plus £3000 to £6000 to pay a locum or other doctors who take over the work in the practice. Board members will be …
Role of a pituitary-specific transcription factor (pit-1/GHF-1) or a closely related protein in cAMP regulation of human thyrotropin-beta subunit gene expression.
Authors: H J Steinfelder, S Radovick, M A Mroczynski, P Hauser, J H McClaskey, B D Weintraub, F E Wondisford
Journal: Journal of Clinical Investigation (1992)

cAMP regulation of the human thyrotropin-beta (TSH beta) gene cAMP was studied in two heterologous cell lines, a human embryonal kidney cell line (293) and a rat pituitary cell line (GH3). In 293 cells, human TSH beta gene expression was not stimulated by the adenylate cyclase activator forskolin or the cAMP analogue 8-bromo-cAMP (8-Br-cAMP). On the other hand, these agents induced human TSH beta gene expression 4-12-fold in GH3 cells. Deletion analysis demonstrated that the regions from +3 to +8 bp and from -128 to -61 bp were both necessary for cAMP stimulation. The latter region contains three DNA sequences homologous to a pituitary-specific transcription factor, Pit-1/GHF-1, DNA-binding site. Gel-mobility assays demonstrated that a radiolabeled human TSH beta probe (-128 to -61 bp) formed five specific DNA-protein complexes with mouse thyrotropic tumor (MTT) nuclear extract and two specific complexes with in vitro translated Pit-1/GHF-1. Four of the five MTT complexes and both in vitro Pit-1/GHF-1 complexes were reduced or eliminated by excess of an unlabeled Pit-1/GHF-1 DNA-binding site from the rat growth hormone gene, but not a mutated version of the same DNA fragment, suggesting that Pit-1/GHF-1 or a closely related thyrotroph protein binds to these DNA sequences. In 293 cells, co-transfection of an expression vector containing the Pit-1/GHF-1 cDNA restored cAMP-responsiveness to the human TSH beta promoter (5.2- and 6.6-fold maximal stimulation by 8-Br-cAMP and forskolin, respectively) but not the herpes virus thymidine kinase promoter (1.2-fold maximal stimulation by either agent). Thus we conclude that the human TSH beta gene is positively regulated by cAMP in GH3 but not 293 cells. Since the human TSH beta gene contains at least one high-affinity binding site for Pit-1/GHF-1 in a region necessary for cAMP stimulation and cAMP stimulation could be restored to the human TSH beta promoter in a previously nonresponsive cell line by the addition of Pit-1/GHF-1, this suggests that Pit-1/GHF-1, or a closely related protein in the thyrotroph, may be a trans-acting factor for cAMP stimulation of the TSH beta gene.
Occlusion of Coronary Arteries after Vein Bypass
Authors: M. R. MALINOW, E. LOUISE KREMKAU, F. E. KLOSTER, L. I. BONCHEK, J. RÖSCH
Journal: Circulation (1973)

The coronary arteries of 100 patients were radiographically visualized by selective injection of contrast material. Findings in the three main arteries (left anterior descending, right, and circumflex arteries) were analyzed before and after aortocoronary-saphenous vein graft surgery. Proximal coronary artery stenosis progressed to complete occlusion in almost half the patients on whose stenotic arteries a graft had been placed. The incidence was higher than that observed in nongrafted arteries during the "natural" course of the disease. The frequency of occlusion in grafted coronary arteries was higher in severely stenotic than in moderately stenotic arteries. The fact that the occlusion occurred more often with a patent graft than with a closed graft suggests a hemodynamic component in its pathogenesis. The study indicates that in many patients the prognosis must remain linked to patency of the bypass graft.
Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis.
Authors: M Heras, J H Chesebro, M W Webster, J S Mruk, D E Grill, W J Penny, E J Bowie, L Badimon, V Fuster
Journal: Circulation (1990)

Three dosages (0.3, 0.7, and 1.0 mg/kg) of recombinant hirudin, a specific inhibitor of thrombin, were compared with heparin (50 units/kg) and placebo for reducing thrombus formation in the carotid arteries of 50 pigs after deep injury by balloon dilatation. Each drug was administered as a bolus followed immediately by a continuous infusion of the same dose per hour. Major end points were quantitative indium-111-labeled platelet and iodine-125-labeled fibrinogen deposition and the incidence of mural thrombosis. This study showed that heparin, at a dose that prolonged the activated partial thromboplastin time (APTT) to twice the control time, did not prevent mural thrombosis or significantly reduce platelet deposition compared with placebo but did reduce fibrinogen deposition. Recombinant hirudin markedly reduced platelet and fibrinogen deposition in a dose-related manner and totally eliminated mural thrombosis at an APTT of two to three times that of control. Platelet deposition (x 10(6)/cm2, mean +/- SEM) in areas of deep arterial injury for the placebo, heparin, and 0.3, 0.7, and 1.0 mg/kg hirudin groups was 54 +/- 21, 33 +/- 9, 22 +/- 6, 8 +/- 1, and 7 +/- 1, respectively; electron microscopy showed a single layer (or less) of platelets at the two highest hirudin dosages. The incidence of macroscopic mural thrombosis was 76% with placebo, 57% with heparin, 46% with 0.3 mg/kg hirudin; there were no thrombi with 0.7 or 1.0 mg/kg hirudin (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Shifting attention to the flash-lag effect
Authors: Marcus Vinícius C. Baldo, Stanley A. Klein
Journal: Behavioral and Brain Sciences (2008)

Abstract An attention shift from a stationary to a changing object has to occur in feature – rather than physical – space, in order to bind these stimuli into a unitary percept. This time-consuming shift leads to the perception of a changing stimulus further ahead along its trajectory. This attentional framework is able to accommodate the flash-lag effect in its multiple empirical manifestations.
A DNA-PKcs mutation in a radiosensitive T–B– SCID patient inhibits Artemis activation and nonhomologous end-joining
Authors: Mirjam van der Burg, Hanna IJspeert, Nicole S. Verkaik, Tuba Turul, Wouter W. Wiegant, Keiko Morotomi-Yano, Pierre-Olivier Mari, Ilhan Tezcan, David J. Chen, Malgorzata Z. Zdzienicka, Jacques J.M. van Dongen, Dik C. van Gent
Journal: Journal of Clinical Investigation (2008)

Radiosensitive T–B– severe combined immunodeficiency (RS-SCID) is caused by defects in the nonhomologous end-joining (NHEJ) DNA repair pathway, which results in failure of functional V(D)J recombination. Here we have identified the first human RS-SCID patient to our knowledge with a DNA-PKcs missense mutation (L3062R). The causative mutation did not affect the kinase activity or DNA end-binding capacity of DNA-PKcs itself; rather, the presence of long P-nucleotide stretches in the immunoglobulin coding joints indicated that it caused insufficient Artemis activation, something that is dependent on Artemis interaction with autophosphorylated DNA-PKcs. Moreover, overall end-joining activity was hampered, suggesting that Artemis-independent DNA-PKcs functions were also inhibited. This study demonstrates that the presence of DNA-PKcs kinase activity is not sufficient to rule out a defect in this gene during diagnosis and treatment of RS-SCID patients. Further, the data suggest that residual DNA-PKcs activity is indispensable in humans.
Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study
Authors: Brian V. Balgobind, Susana C. Raimondi, Jochen Harbott, Martin Zimmermann, Todd A. Alonzo, Anne Auvrignon, H. Berna Beverloo, Myron Chang, Ursula Creutzig, Michael N. Dworzak, Erik Forestier, Brenda Gibson, Henrik Hasle, Christine J. Harrison, Nyla A. Heerema, Gertjan J. L. Kaspers, Anna Leszl, Nathalia Litvinko, Luca Lo Nigro, Akira Morimoto, Christine Perot, Rob Pieters, Dirk Reinhardt, Jeffrey E. Rubnitz, Franklin O. Smith, Jan Stary, Irina Stasevich, Sabine Strehl, Takashi Taga, Daisuke Tomizawa, David Webb, Zuzana Zemanova, C. Michel Zwaan, Marry M. van den Heuvel-Eibrink
Journal: Blood (2009)
ULCERATIVE COLITIS: A SURVEY OF NINETY-FIVE CASES
Authors: T. L. Hardy, E. Bulmer
Journal: BMJ (1933)

TREATMENT OF ACUTE HIEAD INJURIFS[ MEDICALJ concerning it.A number of patients who are going to make uninterrupted recoveries have very slow pulse rates indeed, it is quite impossible to tell from the initial pulse rate alone what the prognosis of the case is going to be.It is true that a very slow pulse rate is a danger signal, but it can very well be a false alarm.A.-Pulse rate on admission of a series of fatal cases: 64, 88, 96, 80
EBV‐associated lymphoma and chronic inflammatory demyelinating polyneuropathy in an adult without overt immunodeficiency
Authors: Yvette L. Kasamon, Thanh N. Nguyen, Jennifer A. Chan, Alessandra F. Nascimento
Journal: American Journal of Hematology (2002)

Abstract Epstein‐Barr virus (EBV)‐associated lymphoproliferative disease occurs almost exclusively in immunocompromised states. This type of malignancy nevertheless developed in a woman without overt immunocompromise. She presented with rapidly progressive lower extremity weakness that was consistent with a chronic inflammatory demyelinating polyneuropathy (CIDP). CIDP has been documented in Hodgkin's disease but rarely in non‐Hodgkin's disease. Diagnosis was confirmed by lymph node and sural nerve biopsies and by nerve conduction studies. Prednisone, rituximab, cyclophosphamide, doxorubicin, and etoposide were administered with regression of lymphadenopathy and improvement in neurologic symptoms. EBV‐associated lymphoproliferative disease can thus develop in the absence of overt immunodeficiency and may trigger a demyelinating polyneuropathy. Am. J. Hematol. 69:289–293, 2002. © 2002 Wiley‐Liss, Inc.
White Coat Hypertension
Authors: E. C. Abbott
Journal: JAMA (1988)

To the Editor.  —I read with considerable interest the article by Pickering et al1entitled How Common is White Coat Hypertension? in the Jan 8 issue ofJAMA.  The well-known phenomenon that the authors describe must be taken into consideration before starting a lifetime management program for patients whose blood pressures are elevated in a medical environment. My problem is deciding whether the name of the syndrome is appropriate. Why   hypertension? For several reasons, this name seems to be inappropriate.  First, it focuses on the apparel of the physician or nurse. Surely it is not the wearing of a white coat that elevates the blood pressure. Pickering and coworkers made no mention of whether their physicians and technicians were actually wearing white coats during the study. Most general practioners in this area of Canada do not wear white coats. At a recent continuing medical education lecture on
Expression of Renin-Angiotensin System Components in the Heart, Kidneys, and Lungs of Rats With Experimental Heart Failure
Authors: Federico Pieruzzi, Zaid A. Abassi, Harry R. Keiser
Journal: Circulation (1995)

Background Chronic activation of the renin-angiotensin system (RAS) plays an important role in the pathogenesis of heart failure. Increasing evidence indicates that other than the circulating RAS, a local RAS exists in several tissues, including the heart. The present study was carried out to quantify cardiac, renal, and pulmonary mRNA levels of renin, angiotensin-converting enzyme (ACE), and types 1 and 2 angiotensin II receptors (AT-1 and AT-2), in rats with different severities of heart failure. Methods and Results Heart failure was induced by the creation of an aortocaval fistula below the renal arteries. Rats with aortocaval fistula either compensate and maintain a normal sodium balance or decompensate and develop severe sodium retention. Six days after placement of the aortocaval fistula, heart weight (normalized to body weight) increased 35% ( P &lt;.05) in compensated and 65% in decompensated rats compared with control rats. Plasma renin activity increased 45% ( P &lt;.05) in rats in sodium balance and 127% in sodium-retaining rats. Total RNA was extracted from the heart, kidneys, and lungs, followed by reverse transcription–quantitative polymerase chain reaction. Renin mRNA levels in the heart, after 40 cycles, increased 68% ( P &lt;.01) and 140% in rats with either compensated or decompensated heart failure, respectively. Renal renin-mRNA levels also increased 130% ( P &lt;.05) in decompensated and only 52% ( P &lt;.05) in compensated animals. ACE-mRNA increased in a similar pattern in the heart but not in either the kidneys or lungs. Moreover, pulmonary, renal, and cardiac ACE immunoreactivity levels, assessed by Western blot analysis, showed the same trend. AT-1 receptor mRNA levels decreased 54% ( P &lt;.05) only in the myocardium of decompensated rats, whereas AT-2 receptor mRNA did not change in any tissue studied. Conclusions The development of heart failure is associated with a remarkable increase in the expression of a local RAS in the heart, which may contribute to the pathogenesis of this clinical syndrome.
Elevated Expression of BIRC6 Protein in Non–Small-Cell Lung Cancers is Associated with Cancer Recurrence and Chemoresistance
Authors: Xin Dong, Dong Lin, Chris Low, Emily A. Vucic, John C. English, John Yee, Nevin Murray, Wan L. Lam, Victor Ling, Stephen Lam, Peter W. Gout, Yuzhuo Wang
Journal: Journal of Thoracic Oncology (2013)

Non-small-cell lung cancer (NSCLC) is an aggressive, highly chemoresistant disease. Reliable prognostic assays and more effective treatments are critically required. BIRC6 (baculoviral inhibitors of apoptosis proteins repeat-containing 6) protein is a member of the inhibitors of apoptosis protein family thought to play an important role in the progression or chemoresistance of many cancers. In this study, we investigated whether BIRC6 expression can be used as a prognostic marker or potential therapeutic target for NSCLC.In a retrospective analysis, BIRC6 protein expression was determined for 78 resected primary NSCLCs and nine benign lung tissues. Twenty-nine chemoresistant or chemosensitive subrenal capsule NSCLC tissue xenografts were assessed for BIRC6 expression, using immunohistochemistry, and 13 of them for BIRC6 gene copy number, using array comparative genomic hybridization analysis. The effect of small interfering RNA-induced BIRC6 knockdown on the growth of human NSCLC cell cultures and apoptosis (in combination with cisplatin) was investigated.Elevated BIRC6 protein expression in NSCLC tissues was associated with poor 3-year relapse-free patient survival, lymph node involvement, and advanced pathological tumor, node, metastasis stage. In patient-derived lung squamous cell carcinoma xenografts, chemoresistance was associated with elevated BIRC6 expression and increased gene copy number. Small interfering RNA-induced BIRC6 down-regulation inhibited growth of the NSCLC cells and sensitized the cells to cisplatin.BIRC6 may play an important role in the malignant progression and chemoresistance of NSCLC. Elevated BIRC6 protein expression may serve as a predictive marker for chemoresistance of NSCLCs and a poor prognostic factor for NSCLC patients. Down-regulation of the BIRC6 gene as a therapeutic approach may be effective, especially in combination with conventional chemotherapeutics.
Pharmacokinetics of alemtuzumab after haploidentical HLA-mismatched hematopoietic stem cell transplantation using in vivo alemtuzumab with or without CD52-positive malignancies
Authors: Kumi Oshima, Yoshinobu Kanda, Fumio Nakahara, Eriko Shoda, Takahiro Suzuki, Yoichi Imai, Takuro Watanabe, Takashi Asai, Koji Izutsu, Seishi Ogawa, Toru Motokura, Shigeru Chiba, Mineo Kurokawa
Journal: American Journal of Hematology (2006)

We recently reported that the addition of in vivo alemtuzumab to the conditioning regimen enables 2- or 3-locus-mismatched hematopoietic stem cell transplantation without an excessive risk of graft rejection or graft-versus-host disease. In a later series of patients, however, one patient with refractory chronic lymphocytic leukemia with large residual tumors at transplantation developed graft rejection. While the peak alemtuzumab concentration in the previous patients without graft rejection was higher than 5 μg/ml, the peak alemtuzumab concentration in this patient was only 1.44 μg/ml. We considered that alemtuzumab was bound to the large residual tumors, which resulted in a low blood concentration of alemtuzumab. Therefore, it is important to debulk tumors before the conditioning regimen for patients with refractory CD52-positive hematological malignancies, or the dose of alemtuzumab should be adjusted by monitoring the blood concentration, when alemtuzumab is used for in vivo T-cell depletion in 2- or 3-locus-mismatched transplantation. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc.
Think tank recommends free personal care for elderly people
Authors: W. Moore
Journal: BMJ (2002)

A centre left think tank, regarded as close in political thinking to the Labour government, has called for all personal care as well as nursing care of elderly people to be free.

In a report published last week, the Institute for Public Policy Research reviews the debates on funding long term care and raising state pensions.

It recommends that the government adopt a policy about to be introduced in Scotland in which the state funds not just nursing care, as now, but also personal care of people in residential homes.

The last Conservative government introduced means testing of elderly people going into residential care in 1993. This has meant that …
Medical advice and management in the Scottish Health Service
Authors: J K W Morrice
Journal: BMJ (1981)

<h3>Objective</h3> Radiation fears following Japan9s 2011 Fukushima nuclear disaster affected levels of physical activity in local children. We assessed the postdisaster versus predisaster weight status in school children and evaluated to what extent school restrictions on outdoor activities that were intended to reduce radiation exposure risk affected child weight. <h3>Participants</h3> We considered children aged 13–15 years from 4 of the 5 secondary schools in Soma City (n=1030, 99.1% of all children in the city), located in 35–50 km from the Fukushima nuclear plant, postdisaster (2012 and 2015) and predisaster (2010). <h3>Methods</h3> Weight status, in terms of body mass index (BMI), percentage of overweight (POW) and incidence of obesity and underweight (defined as a POW ≥20% and ≤−20%, respectively) were examined and compared predisaster and postdisaster using regression models. We also constructed models to assess the impact of school restrictions on outdoor activity on weight status. <h3>Results</h3> After adjustment for covariates, a slight decrease in mean BMI and POW was detected in females in 2012 (−0.37, 95% CI −0.68 to −0.06; and −1.97, 95% CI −3.57 to −0.36, respectively). For male children, obesity incidence increased in 2012 (OR for obesity: 1.45, 95% CI 1.02 to 2.08). Compared with predisaster weight status, no significant weight change was identified in 2015 in either males or females. School restrictions on outdoor activities were not significantly associated with weight status. <h3>Conclusions</h3> 4 years following the disaster, weight status has recovered to the predisaster levels for males and females; however, a slight decrease in weight in females and a slight increase in risk of obesity were observed in males 1 year following the disaster. Our findings could be used to guide actions taken during the early phase of a radiological disaster to manage the postdisaster health risks in adolescent children.