tbuckley/cabot-search huggingface dataset:
An Emerging Role for SPAK in NCC, NKCC, and Blood Pressure Regulation
Authors: Aylin R. Rodan, Chou-Long Huang
Journal: Journal of the American Society of Nephrology (2010)

The cloning of the related sodium chloride (NCC) and sodium potassium 2 chloride (NKCC) co-transporters in the early 1990s ushered in a new era for understanding the mechanisms of renal salt handling.1 Recent research has focused on the phosphoregulation of NCC and the two NKCC co-transporters: NKCC1, which is widely expressed, and NKCC2, which is renal specific. Two closely related kinases, STE20/SPS1-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase-1 (OSR1), seem to play a key role in NCC, NKCC1, and NKCC2 phosphorylation. All three co-transporters are phosphorylated by SPAK and OSR1 on N-terminal cytoplasmic serines and threonines that are conserved among NCC, NKCC1, and NKCC2, and phosphorylation of these residues results in co-transporter activation.2–5

The importance of these phosphorylation events for NCC activity was first demonstrated in Xenopus oocytes, in which mutation of these residues to nonphosphorylatable alanines reduced baseline NCC activity as well as stimulation of NCC by intracellular chloride depletion.6 Similar results were then observed in mammalian cells by Richardson et al. ,7 who also showed that, like NCC, SPAK and OSR1 were activated by low intracellular chloride, and mutation of the SPAK/OSR1-binding site of NCC abolished NCC phosphorylation. These results suggest that specific stimuli activate SPAK and OSR1, which in turn activate NCC by phosphorylating N-terminal threonines and serines.

The link between SPAK and NCC is strengthened by the report of Yang et al. 8 in this issue of JASN . The authors generated SPAK null mice to demonstrate decreased levels …
Integrated Endoplasmic Reticulum Stress Responses in Cancer
Authors: Michel Moenner, Olivier Pluquet, Marion Bouchecareilh, Eric Chevet
Journal: Cancer Research (2007)

Abstract The endoplasmic reticulum (ER) has emerged as a major site of cellular homeostasis regulation, particularly in the unfolded protein response, which is being found to play a major role in cancer and many other diseases. Here, we address ER-mediated signaling and regulations in the context of environmental challenges in cancer, such as hypoxia, angiogenesis, and chemotherapeutic resistance, and we discuss how ER-resident molecular machines become deregulated and involved in cancer-related pathology. Further exploration of how the ER senses, signals, and adapts to stress may redefine and deepen our understanding of its functions in cancer pathobiology. [Cancer Res 2007;67(22):10631–4]
Consensus Meeting on Microdialysis in Neurointensive Care
Authors: Bo-Michael Bellander, Emmanuel Cantais, Per Enblad, Peter Hutchinson, Carl-Henrik Nordstr�m, Claudia Robertson, Juan Sahuquillo, Martin Smith, Nino Stocchetti, Urban Ungerstedt, Andreas Unterberg, Niels Vidiendal Olsen
Journal: Intensive Care Medicine (2004)
A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance--Part 26
Authors: N A Burd, A Jeukendrup, M B Reid, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2011)

Part 26 provides an overview of three supplements with different characteristics of potential contribution to exercise performance and different levels of scientific support for this potential. Methionine is an amino acid with an important role, in addition to its contribution to protein metabolism, namely, as a precursor of creatine. N-acetylcysteine has an important role in glutathione resynthesis and therefore contributes to antioxidant status. Finally, we discuss a new approach to providing carbohydrates in sports supplements – known as multiple transportable carbohydrates (MTC) – which overcomes the usual intestinal absorption limits to allow higher rates of carbohydrate consumed during exercise to be available as a muscle fuel.

### N A Burd

Methionine is an indispensible amino acid that acts as a substrate, much like the other indispensible amino acids, for building functional muscle proteins. It is clear, however, that methionine also holds a unique role, when compared against the other indispensible amino acids, as it serves as a methyl group donor for DNA/RNA intermediates and for the synthesis of cysteine.1 Daily methionine requirement, reported as a constituent of the requirement for total sulphur amino acids, is 13–15 mg/kg-1/day-1 with the risk for toxicity manifesting only at levels exceeding >10-fold excess in humans.2 3 Daily requirements of methionine are easily obtained in the diet due to its widespread abundance in meats, eggs, cheeses, fruits and vegetables. However, vegan athletes may need increased self-awareness of daily methionine intake.4

What purpose does supplemental methionine have in an athlete's diet for enhancing performance/recovery? Very little, provided the athlete is healthy and consuming a …
HIV-1 Nef Is Associated with Complex Pulmonary Vascular Lesions in SHIV-<i>nef</i>–infected Macaques
Authors: John C. Marecki, Carlyne D. Cool, Jane E. Parr, Virginia E. Beckey, Paul A. Luciw, Alice F. Tarantal, Angela Carville, Richard P. Shannon, Adela Cota-Gomez, Rubin M. Tuder, Norbert F. Voelkel, Sonia C. Flores
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

HIV-infected patients with pulmonary arterial hypertension have histologic manifestations that are indistinguishable from those found in patients with idiopathic pulmonary arterial hypertension. In addition, the role of pleiotropic viral proteins in the development of plexiform lesions in HIV-related pulmonary hypertension (HRPH) has not been explored. Simian immunodeficiency virus (SIV) infection of macaques has been found to closely recapitulate many of the characteristic features of HIV infection, and thus hallmarks of pulmonary arterial hypertension should also be found in this nonhuman primate model of HIV.To determine whether pulmonary arterial lesions were present in archived SIV-infected macaque lung tissues from Johns Hopkins University and two National Primate Research Centers.Archived macaque and human lung sections were examined via immunohistochemistry for evidence of complex vascular lesions.Complex plexiform-like lesions characterized by lumenal obliteration, intimal disruption, medial hypertrophy, thrombosis, and recanalized lumena were found exclusively in animals infected with SHIV-nef (a chimeric viral construct containing the HIV nef gene in an SIV backbone), but not in animals infected with SIV. The mass of cells in the lesions were factor VIII positive, and contained cells positive for muscle-specific and smooth muscle actins. Lung mononuclear cells were positive for HIV Nef, suggesting viral replication. Endothelial cells in both the SHIV-nef macaques and patients with HRPH, but not in patients with idiopathic pulmonary arterial hypertension, were also Nef positive.The discovery of complex vascular lesions in SHIV-nef- but not SIV-infected animals, and the presence of Nef in the vascular cells of patients with HRPH, suggest that Nef plays a key role in the development of severe pulmonary arterial disease.
The relationship between personality, theory of planned behaviour and physical activity in individuals with type II diabetes
Authors: Cally A Davies, W Kerry Mummery, Rebekah M Steele
Journal: British Journal of Sports Medicine (2008)

The purpose of the present study was to conduct a process analysis of the effects of personality on physical activity intention and behaviour using the theory of planned behaviour (TPB).Prospective study design with data collected by means of two questionnaires.Data were obtained by means of two questionnaires, the initial questionnaire measured demographic characteristics, TPB constructs, physical activity intention and personality. The 2-week follow-up questionnaire assessed self-report physical activity behaviour. A series of regression analysis were undertaken to identify the relationship between the variables and to determine mediation effects of the TPB constructs.A random sample of individuals with type II diabetes was selected from the Diabetes Australia (Queensland) membership database. A total of 74 complete data sets were obtained.Intention explained 28% of the variance in physical activity behaviour. Attitude, subjective norm and perceived behavioural control (PBC) explained 73% of variance in physical activity intention. Attitude and PBC mediated the relationship between conscientiousness and physical activity intention.These results provide preliminary evidence that targeting constructs proximal to the behaviour (attitudes and PBC) may be effective in overcoming inherent qualities such as personality in order to produce physical activity behaviour change within this sample population.
Antiproliferative Effects of Interferon-αCon1 on Ovarian Clear Cell Adenocarcinoma <b> <i>In vitro</i> </b> and <b> <i>In vivo</i> </b>
Authors: Yumi Takemoto, Hirohisa Yano, Seiya Momosaki, Sachiko Ogasawara, Naoyo Nishida, Sakiko Kojiro, Toshiharu Kamura, Masamichi Kojiro
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We examined the antiproliferative effect of IFN-αCon1 and its mechanism on ovarian clear cell adenocarcinoma in vitro and in vivo. Experimental Design: (a) The effects of IFN-αCon1 on growth, morphology, cell cycle, and type I IFN-α receptor (IFNAR-2) expression were examined on two ovarian clear cell adenocarcinoma cell lines (KOC-5C and KOC-7C) in vitro. (b) KOC-5C or KOC-7C cells were transplanted into nude mice, and changes in tumor volume, tumor weight, apoptosis, necrosis, and microvessel density were investigated. The expression of angiogenesis factors was examined in the serum and the developed tumors. Results: Both cell lines expressed IFNAR-2 mRNA, but its protein was detected only in KOC-7C. In KOC-7C cells, antiproliferative effects were observed in a time- and dose-dependent manner and cell division was blocked at the S phase. The KOC-7C tumors showed decreases in tumor volume and weight; a decreasing tendency in basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and interleukin (IL)-8 protein expression in the tumor; a significant decrease in bFGF and IL-8 protein expression in the serum, and of microvessel density; and significant increase in apoptosis and necrosis in the tumor. In the KOC-5C tumors, these in vitro and in vivo changes were not apparent, and the antiproliferative effects of IFN-αCon1 were not obvious. Conclusions: IFN-αCon1 suppresses tumor proliferation by inducing apoptosis, blocking the cell cycle, and inhibiting tumor angiogenesis. Our findings show that the clinical efficacy of IFN-αCon1 can be predicted by examining IFNAR-2 expression on tumor cells, and the efficacy of IFN-αCon1 treatment can be evaluated by measuring serum bFGF and IL-8 levels.
Evolutionary Convergence in Adaptation of Proteins to Temperature: A4-Lactate Dehydrogenases of Pacific Damselfishes (Chromis spp.)
Authors: Glenn C. Johns, George N. Somero
Journal: Molecular Biology and Evolution (2003)

We have compared the kinetic properties (Michaelis-Menten constant [Km] and catalytic rate constant [kcat]) and amino acid sequences of orthologs of lactate dehydrogenase-A (A4-LDH) from congeners of Pacific damselfishes (genus Chromis) native to cold-temperate and tropical habitats to elucidate mechanisms of enzymatic adaptation to temperature. Specifically, we determined whether the sites of adaptive variation and the types of amino acids involved in substitutions at these sites were similar in the Chromis orthologs and other orthologs of warm-adapted and cold-adapted A4-LDH previously studied. We report striking evolutionary convergence in temperature adaptation of this protein and present further support for the hypothesis that enzyme adaptation to temperature involves subtle amino acid changes at a few sites that affect the mobility of the portions of the enzyme that are involved in rate-determining catalytic conformational changes. We tested the predicted effects of differences in sequence using site-directed mutagenesis. A single amino acid substitution in a key hinge region of the A4-LDH molecule is sufficient to change the kinetic characteristics of a temperate A4-LDH to that of a tropical ortholog. This substitution is at the same location that was identified in previous studies of adaptive variation in A4-LDH and was hypothesized to be important in adjusting Km and kcat. Our results suggest that certain sites within an enzyme, notably those that establish the energy changes associated with rate-limiting movements of protein structure during catalysis, are "hot spots" of adaptation and that common types of amino acid substitutions occur at these sites to adapt structural "flexibility" and kinetic properties. Thus, despite the wide array of options that proteins have to adjust their structural stabilities in the face of thermal stress, the adaptive changes that couple "flexibility" to alterations of function may be limited in their diversity.
Eosinophilic transient synovitis.
Authors: A I Al-Dabbagh, B Al-Irhayim
Journal: Annals of the Rheumatic Diseases (1983)

Eosinophils are rarely found in either the synovial fluid or the synovial membrane.Ropes and Bauer' found less than 1 % eosinophils in all but 2 of 1200 synovial fluid samples which they examined.Naib2 did not find eosinophils in synovial fluid in a variety of disorders.However, significant eosinophilia of synovial fluid has been reported in single cases as a result of arthrography,3 metastatic adenocarcinoma,4 guinea-worm infestation,5 and radiation.6Patients with rheumatoid arthritis may develop peripheral eosinophilia not as a primary event but in association with extra-articular manifestation.7-12However, even in such cases eosinophils are rarely detected in the synovial tissues.10 11Thus synovial fluid possibly does not mirror the peripheral blood eosinophil count."3The present communication is a report of an atopic child with peripheral blood eosinophilia and mono- arthritis.There were large numbers of eosinophils in the synovial fluids and membrane.The disease was self-limiting and defied classification into any of the known categories.So far as we could ascertain from the English-language literature up to 1980 such an arthritis has not been reported in an atopic individual. Case reportA 1 0-year-old male child, the son of an Indian profes- sor working in Mosul, was brought to the Outpatient Department of Mosul Republican Hospital on 18 April 1979 with a complaint of pain and swelling of the left knee joint,, and with no history of antecedent trauma.The child had been complaining of slight pain during walking for 5 days.There was no history of fever or morning stiffness, but the child had suffered repeated attacks of nasal and pharyngeal catarrh, the last being about 8 months previously.The father had a similar history of upper respiratory catarrh of long duration associated with peripheral blood eosino- philia.He recalled a severe 'eosinophilia problem' once.The grandfather also used to suffer from upper
Risks and benefits of biologic therapy for inflammatory bowel diseases
Authors: G. D'Haens
Journal: Gut (2007)

Methods of infant pulmonary function testing (IPFT) represent an important diagnostic tool for an assessment of chronic lung disease in infancy (CLDI). We assessed lung function in a cohort of children with a perinatal burden. We tested 74 infants and toddlers (birth weight 1.47±1.11kg [mean±SD]; body length at birth 30.8±16.3cm with CLDI. Age at testing was 1.38±0.69 (median 1.35) yrs; body weight 9.0±2.2kg, body length 76.0±9.7cm. The whole-body plethysmography (to measure FRCp and sReff), tidal breathing analysis (tPTEF%tE), baby resistance/compliance (specific Crs) and rapid thoraco-abdominal compression method (VmaxFRC) were performed. MS Baby Body, VIASYS, USA was used. Standard protocols [1] and proper reference values [2] were used. FRCp equals 115.3±41.2% pred (P&lt;0.02), sReff reached 134.6±93.8% pred (P&lt;0.005). A parameter of tPTEF%tE mildly decreased (23.5±10.6%). Specific compliance rs (Crs/kg) was 14.4±3.9 ml/kPa/kg; V9maxFRC reached 136±69 ml/sec. In infants and toddlers with a perinatal burden peripheral and central airway obstruction with mild (secondary) hyperinflation was found. Mildly increased specific compliance of the respiratory system was also found. No restrictive pattern was detected. Serial IPFT assessments in our cohort is required to validate present data. <b>References:</b> 1Hammer J, Eber E (eds). Pediatric Pulmonary Function Testing, 2005, Basel, Karger. 2Hulskamp G et al: Am J Respir Crit Care Med 2003;168:1003-9. Supported by the project "Follow-up of children with perinatal burden" of EEA and Norway grants and by the grant NT/11444-5.
Activity of Daunomycin in Solid Tumors
Authors: Daniel D. Von Hoff
Journal: JAMA (1976)

To the Editor.—  In the concise review of the cardiac effects of doxorubicin hydrochloride (Adriamycin) by Ugoretz (236:295, 1976), it was stated that daunomycin does not have as wide a spectrum of antitumor activity as dexorubicin. This point is a commonly held misconception and has been perpetuated in other publications. 1   The results of a recent review performed by the Investigational Drug Branch of the National Cancer Institute on the activity of daunomycin in solid tumors are shown in the Table. It is apparent from the Table that there has been only a small number of patients treated with daunomycin in each solid tumor category. Not one of the solid tumors has had an adequate trial with daunomycin in a single study.  In reality, then, we do not have enough information to actually say whether daunomycin is active or inactive in solid tumors. With this lack of a data base
Electrical Impedance Scanning for the Early Detection of Breast Cancer in Young Women: Preliminary Results of a Multicenter Prospective Clinical Trial
Authors: Alexander Stojadinovic, Aviram Nissan, Zahava Gallimidi, Sarah Lenington, Wende Logan, Margarita Zuley, Arieh Yeshaya, Mordechai Shimonov, Moshe Melloul, Scott Fields, Tanir Allweis, Ron Ginor, David Gur, Craig D. Shriver
Journal: Journal of Clinical Oncology (2005)

To evaluate the feasibility and patient satisfaction with electrical impedance scanning (EIS) for early detection of breast cancer in young women.Women undergoing screening clinical breast examination, imaging, or biopsy were eligible for EIS examination with T-Scan 2000ED (Mirabel Medical Systems, Austin, TX). Multiple logistic regression analysis evaluated the association between clinical variables and EIS performance. Patients completed a screening EIS satisfaction questionnaire (1 = least satisfied to 5 = most satisfied).Twenty-nine cancers were identified among 1,103 women. Sixty-six percent (19 of 29) of cancers were nonpalpable and 55% (16 of 29) were in women age < or = 50 years. EIS sensitivity and specificity in women younger than 40 years was 50% and 90%, respectively. Exogenous estrogen use (P < .001) and menopausal status (P = .007) correlated significantly with EIS performance. False-positive rates were increased in postmenopausal women and those taking exogenous hormones. No correlation was evident between EIS performance and family history, prior breast cancer, breast density, or palpability. EIS-positive women younger than age 40 were 4.5 times more likely to have breast carcinoma than were women randomly selected from the general population. Patients were highly satisfied with the comfort, speed, and reporting of EIS screening (mean score, 4.8).EIS seems promising for early detection of breast cancer, and identification of young women at increased risk for having the disease at time of screening. Positive EIS-associated breast cancer risk compares favorably with relative risks of conditions commonly used to justify early breast cancer screening. Patients are satisfied with a screening paradigm involving breast EIS.
Detection of myocardial injury during radiofrequency catheter ablation by measuring serum cardiac troponin I levels: procedural correlates
Authors: Antonis S Manolis, Vassilis Vassilikos, Themos Maounis, Helen Melita-Manolis, Lefteris Psarros, Alex Haliasos, Dennis V Cokkinos
Journal: Journal of the American College of Cardiology (1999)
Wnt-Dependent β-Catenin Signaling Is Activated after Unilateral Ureteral Obstruction, and Recombinant Secreted Frizzled-Related Protein 4 Alters the Progression of Renal Fibrosis
Authors: Kameswaran Surendran, Susan Schiavi, Keith A. Hruska
Journal: Journal of the American Society of Nephrology (2005)

beta-Catenin functions as a transducer of Wnt signals to the nucleus, where it interacts with the T cell factor (TCF) family of DNA binding proteins to regulate gene expression. On the basis of the genes regulated by beta-catenin and TCF in various biologic settings, two predicted functions of beta-catenin/TCF-dependent transcription are to mediate the loss of epithelial polarity and to promote fibroblast activities, such as the increased synthesis of fibronectin during chronic renal disease. These predictions were tested by determination of the expression and function of an inhibitor of Wnt signaling, secreted frizzled-related protein 4 (sFRP4), during renal tubular epithelial injury initiated by unilateral ureteral obstruction (UUO). Despite increased sFRP4 gene expression in perivascular regions of injured kidneys, total sFRP4 protein levels decreased after injury. The decreased sFRP4 protein levels after UUO accompanied increased Wnt-dependent beta-catenin signaling in tubular epithelial and interstitial cells, along with increased expression of markers of fibrosis. Administration of recombinant sFRP4 protein caused a reduction in tubular epithelial beta-catenin signaling and suppressed the progression of renal fibrosis, as evidenced by a partial maintenance of E-cadherin mRNA expression and a reduction in the amount of fibronectin and alpha-smooth muscle actin proteins. Furthermore, recombinant sFRP4 reduced the number of myofibroblasts, a central mediator of fibrosis. It is concluded that beta-catenin signaling is activated in tubular epithelial and interstitial cells after renal injury, and recombinant sFRP4 can interfere with epithelial de-differentiation and with fibroblast differentiation and function during progression of renal fibrosis.
Selective tracheobronchial aspiration.
Authors: A A Scott, G Sandham, A S Rebuck
Journal: Thorax (1977)

Eighty attempts at placing suction catheters in the left main bronchus were analysed by studying chest radiographs. When angled catheters were used via a tracheostomy tube the success rate was 75%; the rate fell to 15% when straight tubes were used through an orotracheal tube. Assessment and control of the tube length was found to be important to avoid kinking and subsequent obstruction of the catheters.
Time‐trends in treatment and cardiovascular events in patients with heart failure: a pharmacosurveillance study
Authors: Olav R. de Peuter, Gregory Y.H. Lip, Patrick C. Souverein, Olaf H. Klungel, Anthonius de Boer, Harry R. Büller, Pieter W. Kamphuisen
Journal: European Journal of Heart Failure (2010)