tbuckley/cabot-search huggingface dataset:
Regulation of swelling-activated Cl- current by angiotensin II signalling and NADPH oxidase in rabbit ventricle
Authors: Z. Ren, F. J. Raucci, D. M. Browe, C. M. Baumgarten
Journal: Cardiovascular Research (2007)

We assessed whether hypoosmotic swelling of cardiac myocytes activates volume-sensitive Cl− current (ICl,swell) via the angiotensin II (AngII)-reactive oxygen species (ROS) signalling cascade. The AngII-ROS pathway previously was shown to elicit ICl,swell upon mechanical stretch of β1D integrin. Integrin stretch and osmotic swelling are, however, distinct stimuli. For example, blocking Src kinases stimulates swelling-induced but inhibits stretch-induced ICl,swell. ICl,swell was measured in rabbit ventricular myocytes by whole-cell voltage clamp. Swelling-induced ICl,swell was completely blocked by losartan and eprosartan, AngII type I receptor (AT1) antagonists. AT1 stimulation transactivates epidermal growth factor receptor (EGFR) kinase. Blockade of EGFR kinase with AG1478 abolished both ICl,swell and AngII-induced Cl− current, whereas exogenous EGF evoked a Cl− current that was suppressed by osmotic shrinkage. Phosphatidylinositol 3-kinase (PI-3K) is downstream of EGFR kinase, and PI-3K inhibitors LY294002 and wortmannin blocked ICl,swell. Ultimately, AngII signals via NADPH oxidase (NOX) and superoxide anion, •O2−. NOX inhibitors, diphenyleneiodonium, apocynin and gp91ds-tat, eliminated ICl,swell, whereas scramb-tat, an inactive gp91ds-tat analogue, was ineffective. •O2− rapidly dismutates to H2O2. Consistent with H2O2 being a downstream effector, catalase inhibited ICl,swell, and exogenous H2O2 overcame suppression of ICl,swell by AT1 receptor, EGFR kinase, and PI-3K blockers. H2O2-induced current was not blocked by osmotic shrinkage, however. Activation of ICl,swell by osmotic swelling is controlled by the AngII-ROS cascade, the same pathway previously implicated in ICl,swell activation by integrin stretch. This in part explains why ICl,swell is persistently activated in several models of cardiac disease.
Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation
Authors: Erwin Geuken, Dorien Visser, Folkert Kuipers, Hans Blokzijl, Henri G.D. Leuvenink, Koert P. de Jong, Paul M.J.G. Peeters, Peter L.M. Jansen, Maarten J.H. Slooff, Annette S.H. Gouw, Robert J. Porte
Journal: Journal of Hepatology (2004)
Phase I trial of bortezomib in combination with docetaxel in patients with advanced solid tumors.
Authors: Wells A Messersmith, Sharyn D Baker, Lance Lassiter, Rana A Sullivan, Kimberly Dinh, Virna I Almuete, John J Wright, Ross C Donehower, Michael A Carducci, Deborah K Armstrong
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: Bortezomib (PS-341), a first-in-class proteasome inhibitor, is metabolized by deboronation involving cytochrome P4503A (CYP3A), which also metabolizes docetaxel. Preclinical studies have shown synergy between bortezomib and taxanes. We conducted a phase I study combining bortezomib and docetaxel in refractory solid tumor patients. EXPERIMENTAL DESIGN: Patients received escalating doses of weekly docetaxel (days 1 and 8) and twice weekly bortezomib (days 2, 5, 9, and 12) in 3-week cycles. Two subjects were enrolled at each dose level, with cohort expansion to six for dose-limiting toxicity (DLT). Dose levels 1, 2, and 3 consisted of docetaxel/bortezomib 25/0.8, 25/1.0, and 30/1.0 mg/m(2), respectively. CYP3A activity and docetaxel pharmacokinetic studies were conducted, and proteasome inhibition was assessed. RESULTS: Fourteen patients received a total of 34 cycles of treatment. Dose level 2 was expanded for DLT that occurred in two of six patients consisting of febrile neutropenia in one patient and grade 3 thrombocytopenia in one patient. One patient received two cycles at dose level 3 with dose reduction to dose level 2, where grade 3 thrombocytopenia occurred at cycle 3. Both episodes of grade 3 thrombocytopenia were transient (&amp;lt;7 days). Dose level 1 was then expanded to six patients where no DLTs occurred. CYP3A activity and docetaxel clearance did not change between weeks 1 and 5. CONCLUSIONS: The maximum tolerated dose was docetaxel 25 mg/m(2) (days 1 and 8) with bortezomib 0.8 mg/m(2) (days 2, 5, 9, and 12) given every 21 days. Bortezomib treatment did not alter CYP3A activity and docetaxel clearance.
Controversy on drugs affecting ATP sensitive potassium channel in ischaemic heart disease
Authors: R. Baghdady, C. G Nichols
Journal: Cardiovascular Research (1994)

Journal Article Controversy on drugs affecting ATP sensitive potassium channel in ischaemic heart disease Get access Rose Baghdady, Rose Baghdady Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Colin G Nichols Colin G Nichols Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 1, January 1994, Pages 135–136, https://doi.org/10.1093/cvr/28.1.135 Published: 01 January 1994
Urinary Albumin Excretion and Its Relation With C-Reactive Protein and the Metabolic Syndrome in the Prediction of Type 2 Diabetes
Authors: Auke H. Brantsma, Stephan J.L. Bakker, Hans L. Hillege, Dick de Zeeuw, Paul E. de Jong, Ronald T. Gansevoort
Journal: Diabetes Care (2005)

OBJECTIVE—To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes. RESEARCH DESIGN AND METHODS—We used data from the Prevention of Renal and Vascular End Stage Disease (PREVEND) study, an ongoing, community-based, prospective cohort study initiated in 1997 in the Netherlands. The initial cohort consisted of 8,592 subjects. After 4 years, 6,894 subjects participated in a follow-up survey. Subjects with diabetes at baseline or missing data on fasting glucose were excluded, leaving 5,654 subjects for analysis. The development of type 2 diabetes, defined as a fasting glucose ≥7.0 mmol/l and/or the use of antidiabetic medication, was used as the outcome measure. UAE was calculated as the mean UAE from two consecutive 24-h urine collections. Logistic regression models were used, with the development of type 2 diabetes as the dependent variable. RESULTS—Of the 5,654 subjects for whom data were analyzed, 185 (3.3%) developed type 2 diabetes during a mean follow-up period of 4.2 years. UAE, CRP, and the presence of the metabolic syndrome at baseline were significantly associated with the incidence of type 2 diabetes (P &amp;lt; 0.001 for all variables). In a univariate model, the odds ratio (OR) for UAE was 1.59 (95% CI 1.42–1.79). In our full model, adjusted for age, sex, number of criteria of metabolic syndrome, and other known risk factors for the development of type 2 diabetes (including fasting insulin), the association between UAE and type 2 diabetes remained significant (OR 1.53, 95% CI 1.25–1.88, P &amp;lt; 0.001). There was a significant interaction between UAE and CRP (P = 0.002). After CRP was stratified into tertiles, the ORs for the association between baseline UAE and the development of type 2 diabetes were 2.2 (1.47–3.3), 1.33 (0.96–1.84), and 1.04 (0.83–1.31) for the lowest to highest tertiles, respectively. CONCLUSIONS—UAE predicts type 2 diabetes independent of the metabolic syndrome and other known risk markers of development of type 2 diabetes. The predictive value of UAE was modified by the level of CRP.
Graft-Versus–Ewing Sarcoma Effect and Long-Term Remission Induced by Haploidentical Stem-Cell Transplantation in a Patient With Relapse of Metastatic Disease
Authors: Ewa Koscielniak, Ute Gross-Wieltsch, Joern Treuner, Peter Winkler, Thomas Klingebiel, Peter Lang, Peter Bader, Dietrich Niethammer, Rupert Handgretinger
Journal: Journal of Clinical Oncology (2004)

TO THE EDITOR: The chance of cure is very low for patients with primary metastatic or relapsed rhabdomyosarcoma or Ewing tumors. 1-3 In the German multicenter studies CWS-81, -86, -91, and -96, patients older than 10 years at diagnosis with bone or bone marrow metastases had a 5-year event-free survival of 2%. 4 This poor outcome is due mainly to the high relapse rate after initial chemotherapy, and patients in remission after double high-dose chemotherapy (HDC) had a median time to relapse of 5.7 months (range, 3 to 9 months). Unfortunately, there is no single survivor registered after relapse. 4 Allogeneic transplantation might provide a possible graft-versustumor effect, and regression of metastatic lesions has been documented in patients with solid tumors. 5-8 To exert a graft-versus-tumor effect, we have performed allogeneic transplantation using a haploidentical donor in a patient with metastatic Ewing sarcoma who relapsed after double HDC. A previously healthy 15-year-old girl was diagnosed in April 1998 with a disseminated Ewing sarcoma. Magnetic resonance imaging (MRI) scans showed a 10 11-cm tumor originating from the thorax wall, with erosion and destruction of the 11th rib, with penetration into the retropleural thoracic and retrocrural space. It extended caudally to the upper left kidney pole and spleen, and laterally into the foramina intervertebralia between Th7 and Th11. Skeletal imaging showed metastatic lesions in the eighth rib and in vertebrae C7, Th1, Th5, Th6, Th7, and L5. A chemotherapy scan showed four lung nodules. Bone marrow aspirated from the right and left posterior iliac spines showed massive tumor cell infiltration at both sites. After initial chemotherapy, an almost complete remission was achieved (only residual tumor was seen in the primary site in the 11th rib), and she received consolidation with double HDC and autologous hematopoietic stem-cell rescue. MRI after the second HDC showed residual tumor in the 11th rib, which was locally irradiated. The patient remained well for 8 months when routine imaging showed a large new lytic lesion in the right parietal bone (Fig 1A), with a component occupying the extradural space (Fig 1B).
Phase II study of combination human recombinant GM-CSF with intermediate-dose cytarabine and mitoxantrone chemotherapy in patients with high-risk myelodysplastic syndromes (RAEB, RAEBT, and CMML): An Eastern Cooperative Oncology Group Study
Authors: John M. Bennett, Mary S. Young, Jane L. Liesveld, Elisabeth Paietta, Kenneth B. Miller, Hillard M. Lazarus, Robert D. Marsh, William R. Friedenberg, Hussain T. Saba, F. Ann Hayes, Gordon W. Dewald, Wolfgang Hiddemann, Jacob M. Rowe
Journal: American Journal of Hematology (2000)

A Phase II study of GM-CSF with intermediate-dose cytarabine and mitoxantrone was conducted in patients with high-risk myelodysplastic syndrome. It was designed to evaluate if priming with growth factor could increase the efficiency of chemotherapy. In this older population only two of 10 patients achieved a bone marrow CR, including one patient whose leukemic blasts had an “S” phase increase of 2.55× at 48 hr. Unexpected hepatotoxicity was noted. This regimen cannot be recommended for this elderly population of patients. Am. J. Hematol. 66:23–27, 2001. © 2001 Wiley-Liss, Inc.
Diverticulosis of the main bronchi: a rare cause of recurrent bronchopneumonia in a child.
Authors: A Barbato, A Novello, D Zanolin, P Corner, E Talenti
Journal: Thorax (1993)

Diverticulosis of the main bronchi, not associated with other organ abnormalities, developed in a 12 year old child. This abnormality caused recurrent bronchopneumonia in the lung with the main bronchi diverticulosis. Fibreoptic bronchoscopy helped to locate the lesion and selective bronchography, with injection of contrast medium through the suction channel of the fibreoptic bronchoscope, showed the morphology of this rare malformation.
Dynamic spread of happiness in a large social network: longitudinal analysis over 20 years in the Framingham Heart Study
Authors: J. H Fowler, N. A Christakis
Journal: BMJ (2008)

To evaluate whether happiness can spread from person to person and whether niches of happiness form within social networks.Longitudinal social network analysis.Framingham Heart Study social network.4739 individuals followed from 1983 to 2003.Happiness measured with validated four item scale; broad array of attributes of social networks and diverse social ties.Clusters of happy and unhappy people are visible in the network, and the relationship between people's happiness extends up to three degrees of separation (for example, to the friends of one's friends' friends). People who are surrounded by many happy people and those who are central in the network are more likely to become happy in the future. Longitudinal statistical models suggest that clusters of happiness result from the spread of happiness and not just a tendency for people to associate with similar individuals. A friend who lives within a mile (about 1.6 km) and who becomes happy increases the probability that a person is happy by 25% (95% confidence interval 1% to 57%). Similar effects are seen in coresident spouses (8%, 0.2% to 16%), siblings who live within a mile (14%, 1% to 28%), and next door neighbours (34%, 7% to 70%). Effects are not seen between coworkers. The effect decays with time and with geographical separation.People's happiness depends on the happiness of others with whom they are connected. This provides further justification for seeing happiness, like health, as a collective phenomenon.
Effect of gonadectomy on epidermal growth factor values in the gastrointestinal tract of male and female CD-1 mice.
Authors: M Sayegh, J B Elder
Journal: Gut (1995)

The effects of gonadectomy on the epidermal growth factor (EGF) concentrations in the gastrointestinal tract of CD-1 mice were studied. The EGF concentrations in the gastrointestinal tissues were always higher in males than in females. Gonadectomy led to a decrease in the EGF concentration in males, and an increase in females. Gonadectomy with sialoadenectomy led to a decrease in the EGF concentrations in the gastrointestinal tract of both sexes; the most significant effect being observed in the stomach. Orchidectomy led to a decrease in total body weight, and to a significant decrease in the weight and the protein concentration (ng.g-1 wet weight of tissue) of the submandibular gland, but had no significant effect on the other tissues of the gastrointestinal tract of male mice. Body, tissue weights, and protein concentrations did not change with oophorectomy. This study shows that male and female gonads have a profound effect on the EGF content of the tissues of the gastrointestinal tract and suggests that the submandibular gland also influences the EGF concentration in gastrointestinal tissues in mice.
Studies on mechanisms of interferon-gamma action in pancreatic cancer using a data-driven and model-based approach
Authors: Falko Lange, Katja Rateitschak, Brit Fitzner, Ralf Pöhland, Olaf Wolkenhauer, Robert Jaster
Journal: Molecular Cancer (2011)

Interferon-gamma (IFNγ) is a multifunctional cytokine with antifibrotic and antiproliferative efficiency. We previously found that pancreatic stellate cells (PSC), the main effector cells in cancer-associated fibrosis, are targets of IFNγ action in the pancreas. Applying a combined experimental and computational approach, we have demonstrated a pivotal role of STAT1 in IFNγ signaling in PSC. Using in vivo and in vitro models of pancreatic cancer, we have now studied IFNγ effects on the tumor cells themselves. We hypothesize that IFNγ inhibits tumor progression through two mechanisms, reduction of fibrogenesis and antiproliferative effects on the tumor cells. To elucidate the molecular action of IFNγ, we have established a mathematical model of STAT1 activation and combined experimental studies with computer simulations.In BALB/c-nu/nu mice, flank tumors composed of DSL-6A/C1 pancreatic cancer cells and PSC grew faster than pure DSL-6A/C1 cell tumors. IFNγ inhibited the growth of both types of tumors to a similar degree. Since the stroma reaction typically reduces the efficiency of therapeutic agents, these data suggested that IFNγ may retain its antitumor efficiency in PSC-containing tumors by targeting the stellate cells. Studies with cocultures of DSL-6A/C1 cells and PSC revealed a modest antiproliferative effect of IFNγ under serum-free conditions. Immunoblot analysis of STAT1 phosphorylation and confocal microscopy studies on the nuclear translocation of STAT1 in DSL-6A/C1 cells suggested that IFNγ-induced activation of the transcription factor was weaker than in PSC. The mathematical model not only reproduced the experimental data, but also underscored the conclusions drawn from the experiments by indicating that a maximum of 1/500 of total STAT1 is located as phosphorylated STAT1 in the nucleus upon IFNγ treatment of the tumor cells.IFNγ is equally effective in DSL-6A/C1 tumors with and without stellate cells. While its action in the presence of PSC may be explained by inhibition of fibrogenesis, its efficiency in PSC-free tumors is unlikely to be caused by direct effects on the tumor cells alone but may involve inhibitory effects on local stroma cells as well. To gain further insights, we also plan to apply computer simulations to the analysis of tumor growth in vivo.
Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary disease: an<i>in vitro</i>study
Authors: V.I. Peinado, S. Santos, J. Ramírez, J. Roca, R. Rodriguez-Roisin, J.A. Barberà
Journal: European Respiratory Journal (2002)

Patients with chronic obstructive pulmonary disease (COPD) show impaired hypoxic pulmonary vasoconstriction that might contribute to abnormal gas exchange and could be related to endothelial dysfunction in pulmonary arteries. The aim of the study was to investigate the response of PA to hypoxic stimulus <i>in vitro</i> in COPD, and the role of endothelium-derived nitric oxide (NO) in this response. The pulmonary arteries of 25 patients who underwent lung resection were studied. Patients were divided into controls, COPD+normoxaemia (COPD<sub>N</sub>) and COPD+hypoxaemia (COPD<sub>H</sub>). Hypoxic vasoconstriction (HV) was evaluated before and after stimulation or inhibition of the endothelial release of NO, and in the presence of exogenous NO. Compared with the other groups, HV was reduced in COPD<sub>H</sub>. The magnitude of HV correlated with the oxygen tension in arterial blood. The hypoxic stimulus induced greater contraction after stimulating endothelial release of NO, whereas its inhibition practically abolished HV. Exogenous NO completely inhibited HV. Maximal relaxation induced by endothelium-dependent vasodilators correlated with the magnitude of HV. In conclusion, pulmonary arteries of patients with chronic obstructive pulmonary disease and hypoxaemia have an impaired response to hypoxic stimulus, and the endothelial release of nitric oxide modulates hypoxic vasoconstriction. The depressed response of pulmonary arteries to hypoxia may contribute to abnormal gas exchange in chronic obstructive pulmonary disease.
Renal aspects of therapy for human immunodeficiency virus and associated opportunistic infections.
Authors: J S Berns, R M Cohen, R J Stumacher, M R Rudnick
Journal: Journal of the American Society of Nephrology (1991)

Patients with human immunodeficiency virus infection and the acquired immunodeficiency syndrome are often treated with a variety of potentially nephrotoxic drugs. This review summarizes the renal, fluid, and electrolyte complications of drugs used to treat human immunodeficiency virus and associated opportunistic infections. The pharmacokinetics of the drugs are also briefly reviewed, and dosing guidelines for the use of these drugs in patients who have renal insufficiency or who are receiving dialysis are provided.
Biological Foundations of Language: Clues from Sign Language
Authors: H Poizner, U Bellugi, E S Klima
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Deletion of the Nucleotide Excision Repair Gene <i>Ercc1</i> Reduces Immunoglobulin Class Switching and Alters Mutations Near Switch Recombination Junctions
Authors: Carol E. Schrader, Joycelyn Vardo, Erin Linehan, Michael Z. Twarog, Laura J. Niedernhofer, Jan H.J. Hoeijmakers, Janet Stavnezer
Journal: The Journal of Experimental Medicine (2004)

The structure-specific endonuclease ERCC1-XPF is an essential component of the nucleotide excision DNA repair pathway. ERCC1-XPF nicks double-stranded DNA immediately adjacent to 3′ single-strand regions. Substrates include DNA bubbles and flaps. Furthermore, ERCC1 interacts with Msh2, a mismatch repair (MMR) protein involved in class switch recombination (CSR). Therefore, ERCC1-XPF has abilities that might be useful for antibody CSR. We tested whether ERCC1 is involved in CSR and found that Ercc1−/− splenic B cells show moderately reduced CSR in vitro, demonstrating that ERCC1-XPF participates in, but is not required for, CSR. To investigate the role of ERCC1 in CSR, the nucleotide sequences of switch (S) regions were determined. The mutation frequency in germline Sμ segments and recombined Sμ-Sγ3 segments cloned from Ercc1−/− splenic B cells induced to switch in culture was identical to that of wild-type (WT) littermates. However, Ercc1−/− cells show increased targeting of the mutations to G:C bp in RGYW/WRCY hotspots and mutations occur at sites more distant from the S–S junctions compared with WT mice. The results indicate that ERCC1 is not epistatic with MMR and suggest that ERCC1 might be involved in processing or repair of DNA lesions in S regions during CSR.
CHEMICAL CHANGES OCCURRING IN THE BODY AS A RESULT OF CERTAIN DISEASES IN INFANTS AND CHILDREN
Authors: Alexis F. Hartmann, Dan C. Darrow, Marie Morton
Journal: Journal of Clinical Investigation (1928)

It is well known that in normal subjects the osmotic pressure of the blood serum averages about 310 osmolar millimoles, and varies but little.Since more than 90 per cent of the serum osmotic pressure is due to electrolyte, it is apparent that metabolism of the latter must tend to be such as to maintain a fairly fixed concentration in the blood plasma.Gamble and his coworkers (1) pointed out how constant the level of fixed base in the plasma remained during fasting, and indicated to what extent as a result of experimental pyloric obstruc- tion, reciprocal variation of such anions as Cl' and HCO3' could occur without change in the level of total base.One of us (A.F. H.) (2) also emphasized the same fact in a study of pyloric and intestinal obstruction, intestinal fistulae, and marked vomiting of infants and children.Urinary secretion (or lack of secretion) plays the principal role in this strict maintenance of plasma electrolyte.When urine secretion is too scanty for this purpose as for instance in cases of anhydremia due to diarrhea (3) the level of total electrolyte in the plasma occasionally reaches enormous values.It.is the object of this paper to present data obtained from cases of glomerular nephritis with the idea principally of showing: (1) that in acute hemorrhagic nephritis, marked changes in electrolyte and non- protein nitrogen depend chiefly upon such symptoms as anuria, edema, convulsions and vomiting; (2) that in cases of subacute and chronic 127